Collagen

Evidence-based effects and studies

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Effects
2456
Total evidences
2802

Effects and Evidences

Detailed analysis of research findings

skin hydration

8 evidences

A 12-week within-subject controlled clinical trial (one eye treated, the other as control) found the eye cream containing RFF, N-acetylneuraminic acid and peptides increased periorbital hydration, collagen density and skin elasticity with high participant satisfaction and no adverse effects.

Trust comment: Randomized, within-subject controlled 12-week trial with objective measures (n=37); small sample and product provided by company limit generalizability.

Study Details

PMID:38932444
Participants:37
Impact:+28.1% (treated vs control, 12 weeks)
Trust score:3/5

Daily intake of a fish-collagen + Djulis drink for 8 weeks produced measurable improvements in multiple skin appearance and hydration measures versus placebo.

Trust comment: Randomized double-blind placebo-controlled trial with 50 subjects and reported objective percent changes, though full methodological details (e.g., dropout, measurement methods) are limited in summary text.

Study Details

PMID:32530124
Participants:50
Impact:+17.8% (8 weeks)
Trust score:4/5

A 90-day randomized trial found that ortho-silicic acid stabilized by hydrolyzed marine collagen improved skin firmness, hydration, and texture by clinical assessment.

Trust comment: Randomized, placebo-controlled trial but small sample (n=22) and objective imaging did not show statistical differences.

Study Details

PMID:28941141
Participants:22
Impact:improved (clinical evaluation statistically superior to placebo)
Trust score:3/5

Adults took caviar extract, a caviar+collagen combo, or placebo for 8 weeks; treatment groups showed improved skin moisture, elasticity, whitening and reduced wrinkles with no serious adverse events.

Trust comment: Randomized, double-blind, placebo-controlled human trial with objective measures but small sample (n=45).

Study Details

PMID:38201966
Participants:45
Impact:+6.7% (A.U. 43.09 → 45.98)
Trust score:4/5

Randomized placebo‑controlled 12‑week trial in 72 women: daily drinkable collagen peptides + dermonutrients improved objective measures of skin appearance versus placebo.

Trust comment: Randomized placebo‑controlled trial with objective measures and full follow‑up (n=72); single‑blind design limits blinding strength.

Study Details

PMID:31627309
Participants:72
Impact:+28.0% (T12 vs T0; verum)
Trust score:4/5

12-week randomized double-blind placebo-controlled study found 1650 mg/day of collagen peptide (CPNS) improved skin desquamation, hydration, wrinkling, and elasticity in women with no reported side effects.

Trust comment: Randomized double-blind placebo-controlled human trial (n=100) with time-resolved objective endpoints and reported safety.

Study Details

PMID:36916504
Participants:100
Impact:improved (significant at 4 weeks)
Trust score:4/5

Randomized double-blind placebo-controlled 12-week trial of an oral plant-derived 'collagen alternative' (VC-H1) showing improvements in skin hydration, barrier function, and elasticity.

Trust comment: Well-designed randomized double-blind placebo-controlled trial with objective measures and high compliance, but limited to 12 weeks and a single ethnicity which limits generalizability.

Study Details

PMID:40806423
Participants:98
Impact:increased from 43.1 to 44.7 AU at 12 weeks (+1.6 AU, p<0.001; greater than control)
Trust score:4/5

Oral low-molecular-weight collagen peptide (1 g/day) for 12 weeks improved skin hydration, reduced wrinkles, and increased elasticity in middle-aged women.

Trust comment: Randomized double-blind placebo-controlled trial with objective measures but modest sample size (53 completers) limits generalizability.

Study Details

PMID:29949889
Participants:53
Impact:increased (test vs placebo: 7.23-fold greater at 6 weeks; 2.9-fold greater at 12 weeks; p≤0.003)
Trust score:4/5

skin elasticity (R2)

4 evidences

Randomized double-blind placebo-controlled 12-week trial of an oral plant-derived 'collagen alternative' (VC-H1) showing improvements in skin hydration, barrier function, and elasticity.

Trust comment: Well-designed randomized double-blind placebo-controlled trial with objective measures and high compliance, but limited to 12 weeks and a single ethnicity which limits generalizability.

Study Details

PMID:40806423
Participants:98
Impact:increased from 0.676 to 0.704 at 12 weeks (+0.028, p<0.001; improvement > control)
Trust score:4/5

In older inpatients, daily oral supplement with 10 g collagen peptides for 8 weeks increased forearm skin hydration and elasticity versus control.

Trust comment: Randomized controlled trial with objective blinded measurements but open-label design and small sample (39 analyzed) limits strength.

Study Details

PMID:32195722
Participants:39
Impact:+0.07 (+10.4%) (from 0.67 to 0.74 in intervention)
Trust score:4/5

Daily 5 g collagen peptides enriched in Hyp‑containing motifs for 42 days increased skin elasticity versus normal collagen hydrolysate and showed higher small‑peptide fraction and cellular uptake in digestion/transport models.

Trust comment: Randomized double‑blind design but small sample (n=30) limits generalizability; mechanistic in vitro data support absorption claims.

Study Details

PMID:37970760
Participants:30
Impact:Significant increase in intervention group (R2 reported change ~0.86 to 0.92); control smaller change
Trust score:3/5

Randomized placebo‑controlled 12‑week trial in 72 women: daily drinkable collagen peptides + dermonutrients improved objective measures of skin appearance versus placebo.

Trust comment: Randomized placebo‑controlled trial with objective measures and full follow‑up (n=72); single‑blind design limits blinding strength.

Study Details

PMID:31627309
Participants:72
Impact:+~17.4% (increase from 0.69 to 0.81 at T12)
Trust score:4/5

skin roughness (wrinkle depth)

1 evidences

Randomized placebo‑controlled 12‑week trial in 72 women: daily drinkable collagen peptides + dermonutrients improved objective measures of skin appearance versus placebo.

Trust comment: Randomized placebo‑controlled trial with objective measures and full follow‑up (n=72); single‑blind design limits blinding strength.

Study Details

PMID:31627309
Participants:72
Impact:-26.8% (T12 vs T0; verum)
Trust score:4/5

lumbar spine BMD (L1–L4)

2 evidences

Monthly oral ibandronate increased lumbar spine and hip BMD and reduced bone turnover markers in postmenopausal women on glucocorticoids; vitamin D and calcium were provided to all.

Trust comment: Well‑conducted 12‑month randomized double‑blind placebo‑controlled trial with clear BMD endpoints and biochemical markers.

Study Details

PMID:22803768
Participants:140
Impact:+2.6% at 6 months and +3.2% at 12 months with ibandronate vs +0.3% and −0.1% with placebo (p<0.001)
Trust score:4/5

Randomized double-blind placebo-controlled trial of collagen peptide supplement in postmenopausal women; calcium and vitamin D intake were recommended but not controlled; collagen peptides increased BMD and bone formation markers.

Trust comment: Large (n=131), randomized double‑blind placebo‑controlled 12‑month trial with DXA endpoints and bone biomarkers; appropriate statistical adjustments used.

Study Details

PMID:29337906
Participants:131
Impact:~+3.0% (SCP group over 12 months)
Trust score:5/5

femoral neck BMD

7 evidences

Once-weekly alendronate significantly increased bone mineral density and reduced bone turnover markers versus calcium alone over one year.

Trust comment: Randomized trial in 58 women with clear, clinically relevant BMD and biomarker outcomes, but modest sample size.

Study Details

PMID:16076919
Participants:58
Impact:+5.6% at 12 months
Trust score:4/5

Alendronate prevented glucocorticoid-induced bone loss, increasing BMD at spine and hip sites over 24 weeks compared with calcium alone.

Trust comment: Randomized trial with substantial sample size and clear BMD improvements at multiple sites.

Study Details

PMID:19040000
Participants:140
Impact:+6.3% (24 weeks vs baseline)
Trust score:4/5

Ibandronate and alendronate both increased BMD over 1 year; all women also received daily calcium and vitamin D 200 IU.

Trust comment: Multicenter randomized positive-control trial with 158 randomized (151 completed) and objective BMD/biomarker endpoints; good internal validity.

Study Details

PMID:19855926
Participants:151
Impact:+3.48% (mean increase)
Trust score:4/5

Long-term alfacalcidol (vitamin D analog) increased bone mineral density at spine and hip and lowered parathyroid hormone and bone turnover markers in pre-dialysis CRF patients.

Trust comment: Randomized, double-blind, placebo-controlled trial but small sample size (n=36) limits precision despite clear biochemical and BMD effects.

Study Details

PMID:15031343
Participants:36
Impact:+4.9% vs placebo
Trust score:4/5

In Chinese postmenopausal women, daily fortified milk (1200 mg calcium + vitamin D + FOS-inulin) for 52 weeks increased 25(OH)D, suppressed bone turnover markers and preserved femoral neck BMD compared with regular milk.

Trust comment: Randomized controlled trial with relevant biochemical and BMD outcomes; well-reported markers though intervention included multiple nutrients, not collagen alone.

Study Details

PMID:28975432
Participants:121
Impact:Stable in intervention group vs significant decrease in controls (borderline treatment effect, p=0.07)
Trust score:4/5

Randomized double-blind placebo-controlled trial of collagen peptide supplement in postmenopausal women; calcium and vitamin D intake were recommended but not controlled; collagen peptides increased BMD and bone formation markers.

Trust comment: Large (n=131), randomized double‑blind placebo‑controlled 12‑month trial with DXA endpoints and bone biomarkers; appropriate statistical adjustments used.

Study Details

PMID:29337906
Participants:131
Impact:+6.7% (SCP group over 12 months)
Trust score:5/5

Oral alendronate and yearly zoledronic acid similarly increased bone density and strongly reduced bone resorption biomarkers in adults with osteogenesis imperfecta.

Trust comment: Prospective randomized 24-month study with 52 completers showing consistent BMD gains and large decreases in collagen resorption marker; well-reported outcomes.

Study Details

PMID:27482615
Participants:52
Impact:+13.2% (ALN) / +13.7% (ZOL)
Trust score:4/5

P1NP (bone formation marker)

5 evidences

Randomized double-blind trial in thalassemia patients: weekly alendronate for 12 months increased lumbar (L1–L4) BMD and reduced bone turnover markers versus placebo.

Trust comment: Double-blind randomized controlled design with predefined endpoints and measured biomarkers; modest sample size but well-conducted.

Study Details

PMID:37251676
Participants:47
Impact:Decreased from 82.82 to 45.58 ng/ml (~-37.1%); p=0.006
Trust score:4/5

Intermittent senolytic therapy did not reduce overall bone resorption but transiently increased a bone formation marker and showed benefit in a high-senescent-burden subgroup.

Trust comment: Phase 2 randomized controlled trial with clear endpoints and exploratory subgroup analyses; moderate sample size.

Study Details

PMID:38956196
Participants:60
Impact:+16% at 2 wk and +16% at 4 wk (D+Q vs control, P=0.020 and P=0.024); -9% at 20 wk (NS)
Trust score:4/5

Randomized double-blind placebo-controlled trial of collagen peptide supplement in postmenopausal women; calcium and vitamin D intake were recommended but not controlled; collagen peptides increased BMD and bone formation markers.

Trust comment: Large (n=131), randomized double‑blind placebo‑controlled 12‑month trial with DXA endpoints and bone biomarkers; appropriate statistical adjustments used.

Study Details

PMID:29337906
Participants:131
Impact:increase (significant)
Trust score:5/5

In elderly sedentary men, recreational football increased proximal femur BMD and markers of bone formation and turnover over 12 months.

Trust comment: Randomized small trial with objective BMD and biochemical measures but limited by small group sizes (n≈9 per arm).

Study Details

PMID:24903207
Participants:26
Impact:+40% from baseline after 12 months in football group
Trust score:3/5

Pyridoxamine tended to raise a bone formation marker, increased femoral neck BMD, and slightly lowered HbA1c in older women with T2D.

Trust comment: Double-blind RCT with modest sample size showing significant BMD and HbA1c changes, though some outcomes are borderline.

Study Details

PMID:39376018
Participants:55
Impact:+23.0% with PM vs +4.1% placebo (between-groups P=0.056; within-group PM P=0.028)
Trust score:4/5

dermis density (ultrasound)

1 evidences

16‑week randomized double‑blind trial (90 enrolled, 87 completed) in women: 5 g/day collagen (± HA + vit C) increased dermal density and reduced roughness and wrinkle severity versus placebo.

Trust comment: Well‑conducted randomized double‑blind placebo‑controlled trial with objective ultrasound and topographic outcomes and low dropout rate.

Study Details

PMID:38931263
Participants:87
Impact:+16.3% (CP group vs placebo at 16 weeks)
Trust score:5/5

skin roughness (Ra)

1 evidences

16‑week randomized double‑blind trial (90 enrolled, 87 completed) in women: 5 g/day collagen (± HA + vit C) increased dermal density and reduced roughness and wrinkle severity versus placebo.

Trust comment: Well‑conducted randomized double‑blind placebo‑controlled trial with objective ultrasound and topographic outcomes and low dropout rate.

Study Details

PMID:38931263
Participants:87
Impact:-9.6% (CP group vs placebo at 16 weeks)
Trust score:5/5

wrinkle volume

1 evidences

16‑week randomized double‑blind trial (90 enrolled, 87 completed) in women: 5 g/day collagen (± HA + vit C) increased dermal density and reduced roughness and wrinkle severity versus placebo.

Trust comment: Well‑conducted randomized double‑blind placebo‑controlled trial with objective ultrasound and topographic outcomes and low dropout rate.

Study Details

PMID:38931263
Participants:87
Impact:-13.8% (CP group vs placebo at 16 weeks)
Trust score:5/5

eye wrinkle volume

1 evidences

8‑week double‑blind placebo‑controlled study in 114 women showing specific bioactive collagen peptides (2.5 g/day) reduced eye wrinkle volume and increased dermal procollagen I and elastin.

Trust comment: Randomized double‑blind placebo‑controlled trial with objective imaging and biopsy substudy; moderate sample size and short duration.

Study Details

PMID:24401291
Participants:114
Impact:-20% (vs placebo at 4 and 8 weeks)
Trust score:4/5

procollagen type I content

1 evidences

8‑week double‑blind placebo‑controlled study in 114 women showing specific bioactive collagen peptides (2.5 g/day) reduced eye wrinkle volume and increased dermal procollagen I and elastin.

Trust comment: Randomized double‑blind placebo‑controlled trial with objective imaging and biopsy substudy; moderate sample size and short duration.

Study Details

PMID:24401291
Participants:114
Impact:+65% (verum vs placebo at 8 weeks)
Trust score:4/5

elastin content

2 evidences

8‑week double‑blind placebo‑controlled study in 114 women showing specific bioactive collagen peptides (2.5 g/day) reduced eye wrinkle volume and increased dermal procollagen I and elastin.

Trust comment: Randomized double‑blind placebo‑controlled trial with objective imaging and biopsy substudy; moderate sample size and short duration.

Study Details

PMID:24401291
Participants:114
Impact:+18% (verum vs placebo at 8 weeks)
Trust score:4/5

Both microneedling and fractional CO2 laser improved scar clinical scores and histochemical collagen/elastin; fractional CO2 laser produced larger increases in collagen (neocollagenesis).

Trust comment: Small randomized clinical study (n=30) with histochemical endpoints; limited by small sample size.

Study Details

PMID:34468410
Participants:30
Impact:Increased in both groups after treatment
Trust score:3/5

ADLs (KOOS ADL)

1 evidences

Randomized double‑blind placebo‑controlled study in middle‑aged active adults (86 randomized, 75 completed) testing 0/10/20 g/day collagen peptides showing dose‑ and time‑dependent improvements in function, pain, and mental/physical QoL in subgroups.

Trust comment: Randomized double‑blind trial in active adults with multiple doses and timepoints but moderate sample, subgroup findings, and some statistical assumption violations.

Study Details

PMID:37551682
Participants:75
Impact:improvement (group×time interaction; 10 g/d showed benefit at 6 months)
Trust score:3/5

pain (KOOS Pain)

1 evidences

Randomized double‑blind placebo‑controlled study in middle‑aged active adults (86 randomized, 75 completed) testing 0/10/20 g/day collagen peptides showing dose‑ and time‑dependent improvements in function, pain, and mental/physical QoL in subgroups.

Trust comment: Randomized double‑blind trial in active adults with multiple doses and timepoints but moderate sample, subgroup findings, and some statistical assumption violations.

Study Details

PMID:37551682
Participants:75
Impact:improvement in high‑frequency exercisers with 10 g/d (significant group×time interaction)
Trust score:3/5

mental health (VR-12 MCS)

1 evidences

Randomized double‑blind placebo‑controlled study in middle‑aged active adults (86 randomized, 75 completed) testing 0/10/20 g/day collagen peptides showing dose‑ and time‑dependent improvements in function, pain, and mental/physical QoL in subgroups.

Trust comment: Randomized double‑blind trial in active adults with multiple doses and timepoints but moderate sample, subgroup findings, and some statistical assumption violations.

Study Details

PMID:37551682
Participants:75
Impact:increase (10 g/d showed significant improvements over time)
Trust score:3/5

nasolabial wrinkle score (right cheek)

1 evidences

12‑week randomized triple‑blind placebo‑controlled study (50 randomized, 45 completed) in women showing fish‑derived hydrolyzed collagen (10 g/day) reduced nasolabial wrinkle scores and improved self‑reported skin parameters; elasticity improved in younger subgroup.

Trust comment: Triple‑blind randomized placebo‑controlled trial with objective imaging; modest sample size but clear wrinkle improvement signals.

Study Details

PMID:32799362
Participants:45
Impact:-24% (verum vs placebo at 12 weeks)
Trust score:4/5

nasolabial wrinkle score (within‑group)

1 evidences

12‑week randomized triple‑blind placebo‑controlled study (50 randomized, 45 completed) in women showing fish‑derived hydrolyzed collagen (10 g/day) reduced nasolabial wrinkle scores and improved self‑reported skin parameters; elasticity improved in younger subgroup.

Trust comment: Triple‑blind randomized placebo‑controlled trial with objective imaging; modest sample size but clear wrinkle improvement signals.

Study Details

PMID:32799362
Participants:45
Impact:-17% left, -35% right (verum from baseline to 12 weeks)
Trust score:4/5

cheek skin elasticity (age 45–54 subgroup)

1 evidences

12‑week randomized triple‑blind placebo‑controlled study (50 randomized, 45 completed) in women showing fish‑derived hydrolyzed collagen (10 g/day) reduced nasolabial wrinkle scores and improved self‑reported skin parameters; elasticity improved in younger subgroup.

Trust comment: Triple‑blind randomized placebo‑controlled trial with objective imaging; modest sample size but clear wrinkle improvement signals.

Study Details

PMID:32799362
Participants:45
Impact:+10% (verum vs baseline at 12 weeks)
Trust score:4/5

wrinkle severity (crow's feet, eye wrinkle volume)

1 evidences

Randomized double-blind placebo-controlled trial found that 12 weeks of low-molecular-weight collagen peptide supplementation improved wrinkles, skin roughness, elasticity, hydration, and barrier function.

Trust comment: Well-designed randomized double-blind placebo-controlled trial (100 randomized; 84 per-protocol) with objective measures and safety data.

Study Details

PMID:36516059
Participants:84
Impact:improved (significant at 12 weeks)
Trust score:4/5

skin elasticity (R2, R7)

1 evidences

Randomized double-blind placebo-controlled trial found that 12 weeks of low-molecular-weight collagen peptide supplementation improved wrinkles, skin roughness, elasticity, hydration, and barrier function.

Trust comment: Well-designed randomized double-blind placebo-controlled trial (100 randomized; 84 per-protocol) with objective measures and safety data.

Study Details

PMID:36516059
Participants:84
Impact:improved (significant at 12 weeks)
Trust score:4/5

skin hydration and transepidermal water loss (TEWL) / barrier integrity

1 evidences

Randomized double-blind placebo-controlled trial found that 12 weeks of low-molecular-weight collagen peptide supplementation improved wrinkles, skin roughness, elasticity, hydration, and barrier function.

Trust comment: Well-designed randomized double-blind placebo-controlled trial (100 randomized; 84 per-protocol) with objective measures and safety data.

Study Details

PMID:36516059
Participants:84
Impact:hydration increased; TEWL improved (significant)
Trust score:4/5

skin roughness / wrinkle parameters

1 evidences

12-week randomized double-blind placebo-controlled study showing low-molecular-weight collagen peptides improved skin roughness, elasticity, hydration, and skin whitening measures without adverse events.

Trust comment: Randomized double-blind placebo-controlled human trial (n=100) with multiple objective skin endpoints; results consistent and safety reported.

Study Details

PMID:37822045
Participants:100
Impact:improved (significant at 12 weeks)
Trust score:4/5

skin elasticity (overall, net, biological)

1 evidences

12-week randomized double-blind placebo-controlled study showing low-molecular-weight collagen peptides improved skin roughness, elasticity, hydration, and skin whitening measures without adverse events.

Trust comment: Randomized double-blind placebo-controlled human trial (n=100) with multiple objective skin endpoints; results consistent and safety reported.

Study Details

PMID:37822045
Participants:100
Impact:improved (significant at 12 weeks)
Trust score:4/5

skin hydration and whitening (melanin, erythema indexes)

1 evidences

12-week randomized double-blind placebo-controlled study showing low-molecular-weight collagen peptides improved skin roughness, elasticity, hydration, and skin whitening measures without adverse events.

Trust comment: Randomized double-blind placebo-controlled human trial (n=100) with multiple objective skin endpoints; results consistent and safety reported.

Study Details

PMID:37822045
Participants:100
Impact:improved (significant)
Trust score:4/5

skin elasticity

9 evidences

Adults took caviar extract, a caviar+collagen combo, or placebo for 8 weeks; treatment groups showed improved skin moisture, elasticity, whitening and reduced wrinkles with no serious adverse events.

Trust comment: Randomized, double-blind, placebo-controlled human trial with objective measures but small sample (n=45).

Study Details

PMID:38201966
Participants:45
Impact:+8.9% (R2 0.667 → 0.726)
Trust score:4/5

A 12-week oral chicken sternal cartilage (BioCell Collagen) supplement increased skin collagen and elasticity and reduced wrinkle severity versus placebo.

Trust comment: Well-designed double-blind placebo-controlled RCT with objective measures and 113 completers, though industry/product-specific formulation may limit independent replication.

Study Details

PMID:31221944
Participants:113
Impact:increased (P=.008)
Trust score:4/5

Daily oral nutricosmeceutical (collagen peptides + antioxidants) for 90 days improved skin elasticity and texture versus placebo.

Trust comment: Double-blind randomized placebo-controlled trial with good sample size (n=120); product combined collagen peptides with antioxidants which may confound isolated collagen effect.

Study Details

PMID:28528342
Participants:120
Impact:+7.5% (p ≤ 0.001) vs placebo
Trust score:4/5

In 30 women, combined acupotomy subcision plus hyaluronic acid produced greater increases in skin collagen and elasticity and greater wrinkle improvement than either treatment alone.

Trust comment: Randomized trial in humans with objective measures but small arms (10 per group) and short follow-up.

Study Details

PMID:40296541
Participants:30
Impact:increased at 1 and 6 months; greatest increase in AS+HA group
Trust score:3/5

Adding topical PRP to fractional laser improved patient satisfaction, increased skin elasticity, collagen amount, and fibroblast number on biopsy compared with laser alone.

Trust comment: Small controlled clinical study (n=22) with biopsy and objective skin measures but limited sample size.

Study Details

PMID:22288389
Participants:22
Impact:Improved with PRP + fractional laser (clinical and biophysical measures)
Trust score:3/5

Topical meristem-cell-based serums applied for 4 weeks improved skin hydration, elasticity and increased dermal collagen markers (hydroxyproline) with reduced lipid peroxidation.

Trust comment: Randomized single-blind trial with objective instrumental and biochemical measures but no placebo control and small biopsy subgroup (n=12) for collagen marker.

Study Details

PMID:39334942
Participants:102
Impact:statistically significant improvement after 4 weeks
Trust score:3/5

90-day randomized placebo-controlled trial of a multi-ingredient nutraceutical containing hydrolyzed fish collagen plus other actives showed large improvements in skin elasticity and joint symptoms.

Trust comment: Randomized controlled trial with large reported effects but product contained multiple active ingredients (collagen plus chondroitin, glucosamine, vitamins), so effects cannot be attributed solely to collagen.

Study Details

PMID:30122200
Participants:120
Impact:+40% vs placebo
Trust score:3/5

Daily collagen hydrolysate (2.5 or 5 g) for 8 weeks improved skin elasticity versus placebo in middle-aged women; other skin parameters showed nonsignificant trends.

Trust comment: Double-blind, placebo-controlled RCT with objective skin measures and 69 participants gives moderate-high confidence.

Study Details

PMID:23949208
Participants:69
Impact:+statistically significant improvement vs placebo (both 2.5 g and 5.0 g groups)
Trust score:4/5

Multicenter randomized trial comparing standard skin grafts vs grafts plus cultured autologous epidermal cells seeded in a collagen carrier; assessed healing and scar quality.

Trust comment: Randomized multicenter trial with clinically relevant endpoints (n=40); intervention combined cultured cells with a collagen carrier so effects cannot be attributed to collagen alone.

Study Details

PMID:26419871
Participants:40
Impact:Higher in experimental area at 3 months (P=0.030)
Trust score:3/5

joint pain

1 evidences

90-day randomized placebo-controlled trial of a multi-ingredient nutraceutical containing hydrolyzed fish collagen plus other actives showed large improvements in skin elasticity and joint symptoms.

Trust comment: Randomized controlled trial with large reported effects but product contained multiple active ingredients (collagen plus chondroitin, glucosamine, vitamins), so effects cannot be attributed solely to collagen.

Study Details

PMID:30122200
Participants:120
Impact:-43% (reduction)
Trust score:3/5

joint mobility

1 evidences

90-day randomized placebo-controlled trial of a multi-ingredient nutraceutical containing hydrolyzed fish collagen plus other actives showed large improvements in skin elasticity and joint symptoms.

Trust comment: Randomized controlled trial with large reported effects but product contained multiple active ingredients (collagen plus chondroitin, glucosamine, vitamins), so effects cannot be attributed solely to collagen.

Study Details

PMID:30122200
Participants:120
Impact:+39%
Trust score:3/5

collagen structure (confocal microscopy assessment)

1 evidences

12-week triple-blind randomized placebo-controlled trial in women showed that a drinkable supplement containing collagen peptides and dermonutrients improved dermal collagen structure and subjective skin measures without adverse events.

Trust comment: Randomized triple-blind placebo-controlled trial (n=60) with objective imaging and subjective measures; product included collagen peptides plus vitamins/dermunutrients which may contribute to effects.

Study Details

PMID:32017646
Participants:60
Impact:improved (significant vs placebo)
Trust score:4/5

skin moisture / suppleness / softness (subjective)

1 evidences

12-week triple-blind randomized placebo-controlled trial in women showed that a drinkable supplement containing collagen peptides and dermonutrients improved dermal collagen structure and subjective skin measures without adverse events.

Trust comment: Randomized triple-blind placebo-controlled trial (n=60) with objective imaging and subjective measures; product included collagen peptides plus vitamins/dermunutrients which may contribute to effects.

Study Details

PMID:32017646
Participants:60
Impact:improved (significant)
Trust score:4/5

skin desquamation

1 evidences

12-week randomized double-blind placebo-controlled study found 1650 mg/day of collagen peptide (CPNS) improved skin desquamation, hydration, wrinkling, and elasticity in women with no reported side effects.

Trust comment: Randomized double-blind placebo-controlled human trial (n=100) with time-resolved objective endpoints and reported safety.

Study Details

PMID:36916504
Participants:100
Impact:improved (significant at 4 weeks)
Trust score:4/5

skin wrinkling and elasticity

1 evidences

12-week randomized double-blind placebo-controlled study found 1650 mg/day of collagen peptide (CPNS) improved skin desquamation, hydration, wrinkling, and elasticity in women with no reported side effects.

Trust comment: Randomized double-blind placebo-controlled human trial (n=100) with time-resolved objective endpoints and reported safety.

Study Details

PMID:36916504
Participants:100
Impact:improved (wrinkling significant at 12 weeks; elasticity significant at 12 weeks)
Trust score:4/5

skin moisture

3 evidences

Daily 5 g collagen peptides for up to 84 days improved dermal density and skin moisture versus placebo and produced earlier improvements in elasticity, wrinkle visibility, nail color, and beauty perception.

Trust comment: Double-blind RCT in 85 participants with standardized skincare and objective measures supports moderate confidence.

Study Details

PMID:39143887
Participants:85
Impact:+significant improvement vs placebo at 84 days
Trust score:4/5

In vivo dermatological evaluation of topical formulations containing lyophilized hydrolyzed blue shark cartilage (collagen) applied to inner wrists of volunteers with skin measurements at baseline, 10 min and 20 min.

Trust comment: Human volunteer dermatological test with 66 participants and objective instrument measures but short-term (minutes) assessment limits clinical relevance for sustained effects.

Study Details

PMID:36286457
Participants:66
Impact:formulations tended to increase skin moisture (improvement vs baseline at 10–20 min)
Trust score:3/5

Daily collagen hydrolysate (2.5 or 5 g) for 8 weeks improved skin elasticity versus placebo in middle-aged women; other skin parameters showed nonsignificant trends.

Trust comment: Double-blind, placebo-controlled RCT with objective skin measures and 69 participants gives moderate-high confidence.

Study Details

PMID:23949208
Participants:69
Impact:+positive trend in subgroup analyses (not statistically significant overall)
Trust score:4/5

transepidermal water loss / skin evaporation

1 evidences

Daily collagen hydrolysate (2.5 or 5 g) for 8 weeks improved skin elasticity versus placebo in middle-aged women; other skin parameters showed nonsignificant trends.

Trust comment: Double-blind, placebo-controlled RCT with objective skin measures and 69 participants gives moderate-high confidence.

Study Details

PMID:23949208
Participants:69
Impact:+positive trend in subgroup analyses (not statistically significant overall)
Trust score:4/5

myofibrillar protein synthesis

1 evidences

In recreational athletes, 30 g collagen protein taken after resistance exercise increased circulating glycine/proline but did not increase myofibrillar or muscle connective protein synthesis versus placebo over 5 h.

Trust comment: Well-controlled, randomized, double-blind trial with tracer-based muscle biopsy measures providing high internal validity.

Study Details

PMID:37202878
Participants:45
Impact:no increase with collagen vs placebo (whey increased myofibrillar synthesis)
Trust score:5/5

muscle connective protein synthesis

1 evidences

In recreational athletes, 30 g collagen protein taken after resistance exercise increased circulating glycine/proline but did not increase myofibrillar or muscle connective protein synthesis versus placebo over 5 h.

Trust comment: Well-controlled, randomized, double-blind trial with tracer-based muscle biopsy measures providing high internal validity.

Study Details

PMID:37202878
Participants:45
Impact:no increase with collagen vs placebo during first 5 h postexercise
Trust score:5/5

plasma glycine/proline/hydroxyproline

2 evidences

Fifteen grams hydrolyzed collagen twice daily during 1 week of intense resistance training raised some plasma collagen-related amino acids but did not increase muscle myofibrillar or connective protein synthesis rates.

Trust comment: Randomized, double-blind trial with direct biochemical measurements but small sample and short intervention.

Study Details

PMID:39086044
Participants:25
Impact:+ (post-absorptive concentrations increased)
Trust score:4/5

In recreational athletes, 30 g collagen protein taken after resistance exercise increased circulating glycine/proline but did not increase myofibrillar or muscle connective protein synthesis versus placebo over 5 h.

Trust comment: Well-controlled, randomized, double-blind trial with tracer-based muscle biopsy measures providing high internal validity.

Study Details

PMID:37202878
Participants:45
Impact:+marked increase in circulating glycine, proline, hydroxyproline (higher iAUC after collagen)
Trust score:5/5

dermis density

3 evidences

Daily 2.5 g bioactive collagen peptides for 6 months reduced cellulite severity and improved skin waviness and dermal density, with stronger effects in normal-weight women.

Trust comment: Randomized, placebo-controlled study with objective imaging and 97 completers provides moderate-high reliability, though subgroup effects vary.

Study Details

PMID:26561784
Participants:97
Impact:+significant increase vs placebo after 6 months
Trust score:4/5

Daily 5 g collagen peptides for up to 84 days improved dermal density and skin moisture versus placebo and produced earlier improvements in elasticity, wrinkle visibility, nail color, and beauty perception.

Trust comment: Double-blind RCT in 85 participants with standardized skincare and objective measures supports moderate confidence.

Study Details

PMID:39143887
Participants:85
Impact:+significant improvement vs placebo at 84 days
Trust score:4/5

Daily syrup containing fish collagen (4 g) plus CoQ10 for 12 weeks increased dermis density and reduced periorbital wrinkles and overall wrinkle score vs placebo.

Trust comment: Randomized, double-blind, placebo-controlled trial with objective measures but small sample (31 completers).

Study Details

PMID:32120787
Participants:31
Impact:+5.8 units; +16.1% vs placebo (43.1 ±4.5 vs 37.3 ±4.0)
Trust score:4/5

skin elasticity / wrinkle visibility

1 evidences

Daily 5 g collagen peptides for up to 84 days improved dermal density and skin moisture versus placebo and produced earlier improvements in elasticity, wrinkle visibility, nail color, and beauty perception.

Trust comment: Double-blind RCT in 85 participants with standardized skincare and objective measures supports moderate confidence.

Study Details

PMID:39143887
Participants:85
Impact:earlier positive effects observed in collagen group (improvements seen by 28 days vs placebo by 84 days)
Trust score:4/5

cellulite score

1 evidences

Daily 2.5 g bioactive collagen peptides for 6 months reduced cellulite severity and improved skin waviness and dermal density, with stronger effects in normal-weight women.

Trust comment: Randomized, placebo-controlled study with objective imaging and 97 completers provides moderate-high reliability, though subgroup effects vary.

Study Details

PMID:26561784
Participants:97
Impact:−0.3 points overall after 6 months (≈9% reduction vs placebo in normal BMI subgroup at 6 months)
Trust score:4/5

skin waviness

1 evidences

Daily 2.5 g bioactive collagen peptides for 6 months reduced cellulite severity and improved skin waviness and dermal density, with stronger effects in normal-weight women.

Trust comment: Randomized, placebo-controlled study with objective imaging and 97 completers provides moderate-high reliability, though subgroup effects vary.

Study Details

PMID:26561784
Participants:97
Impact:−8% vs placebo after 6 months (−11.1% in normal BMI subgroup)
Trust score:4/5

activity-related knee pain (VAS)

2 evidences

Randomized double-blind placebo-controlled trial: 5 g/day specific collagen peptides for 12 weeks reduced activity-related knee pain versus placebo in physically active young adults.

Trust comment: Well-powered randomized double-blind placebo-controlled trial with pre-registered design and per-protocol and intention-to-treat analyses, but results apply to a specific collagen peptide formulation.

Study Details

PMID:33562729
Participants:180
Impact:reduced by ~42% in collagen group; statistically greater improvement vs placebo (subject p=0.024; physician p=0.003); effect sizes d≈−0.34 to −0.45
Trust score:4/5

Daily 5 g bioactive collagen peptides for 12 weeks in athletic adults reduced activity-related knee pain versus placebo (significant VAS improvement) and reduced use of additional therapies.

Trust comment: Large sample and measured outcomes support relevance, but design/randomization/blinding details are unclear in provided text, lowering confidence.

Study Details

PMID:28177710
Participants:139
Impact:BCP ΔVAS = 19.5 ± 2.4 vs Placebo ΔVAS = 13.9 ± 2.1 (p = 0.046); significant greater pain reduction with collagen
Trust score:3/5

use of additional therapeutic options

1 evidences

Daily 5 g bioactive collagen peptides for 12 weeks in athletic adults reduced activity-related knee pain versus placebo (significant VAS improvement) and reduced use of additional therapies.

Trust comment: Large sample and measured outcomes support relevance, but design/randomization/blinding details are unclear in provided text, lowering confidence.

Study Details

PMID:28177710
Participants:139
Impact:significant reduction in additional treatment use after collagen intake
Trust score:3/5

resting pain (VAS)

1 evidences

Daily 5 g bioactive collagen peptides for 12 weeks in athletic adults reduced activity-related knee pain versus placebo (significant VAS improvement) and reduced use of additional therapies.

Trust comment: Large sample and measured outcomes support relevance, but design/randomization/blinding details are unclear in provided text, lowering confidence.

Study Details

PMID:28177710
Participants:139
Impact:improved with collagen but not significantly different from placebo
Trust score:3/5

dermis echogenicity / density

1 evidences

Daily 500 mg hydrolyzed fish cartilage for 90 days improved dermis echogenicity and thickness and reduced facial wrinkles and pore measures versus placebo in middle-aged women.

Trust comment: Randomized, double-blind, placebo-controlled design with objective imaging measures supports moderate-high confidence despite modest sample size.

Study Details

PMID:34443468
Participants:43
Impact:+significant increase vs placebo after 90 days (improved echogenicity)
Trust score:4/5

wrinkle severity

4 evidences

Adults took caviar extract, a caviar+collagen combo, or placebo for 8 weeks; treatment groups showed improved skin moisture, elasticity, whitening and reduced wrinkles with no serious adverse events.

Trust comment: Randomized, double-blind, placebo-controlled human trial with objective measures but small sample (n=45).

Study Details

PMID:38201966
Participants:45
Impact:-5.8% (Ra 23.35 μm → 22.01 μm)
Trust score:4/5

Daily 500 mg hydrolyzed fish cartilage for 90 days improved dermis echogenicity and thickness and reduced facial wrinkles and pore measures versus placebo in middle-aged women.

Trust comment: Randomized, double-blind, placebo-controlled design with objective imaging measures supports moderate-high confidence despite modest sample size.

Study Details

PMID:34443468
Participants:43
Impact:reduced wrinkles (frontal −14%, nasolabial −31%, periorbital −26% vs baseline; significant reductions vs placebo at 90 days)
Trust score:4/5

Randomised double-blind study comparing porcine/bovine collagen fillers and hyaluronic acid for upper lip wrinkles; all treatments increased lip volume and reduced wrinkles, Perlane showed greatest and most sustained volume.

Trust comment: Randomised double-blind trial with objective 3D measures and reasonable sample size though single-centre.

Study Details

PMID:18986859
Participants:79
Impact:decrease (all treatments)
Trust score:4/5

Split-face trial in which hyaluronic acid fillers improved nasolabial/crow's-feet wrinkles and showed increased local collagen synthesis and good tolerability up to 180 days.

Trust comment: Prospective, randomized, split-face blinded study with objective measures and moderate sample size; assesses collagen stimulation but not collagen supplementation.

Study Details

PMID:28595250
Participants:61
Impact:statistically significant improvement maintained to D180 (no % reported)
Trust score:4/5

dermis thickness

1 evidences

Daily 500 mg hydrolyzed fish cartilage for 90 days improved dermis echogenicity and thickness and reduced facial wrinkles and pore measures versus placebo in middle-aged women.

Trust comment: Randomized, double-blind, placebo-controlled design with objective imaging measures supports moderate-high confidence despite modest sample size.

Study Details

PMID:34443468
Participants:43
Impact:+significant increase vs placebo after 90 days (suggesting improved hydration)
Trust score:4/5

buccal bony window area reduction

1 evidences

Adding type‑1 collagen particles plus i‑PRF to periapical surgery did not improve bone‑defect healing compared with surgery alone; both groups showed large lesion reductions at 12 months.

Trust comment: Randomized controlled trial, registered and followed 12‑month radiographic endpoints; moderate sample size limits precision.

Study Details

PMID:37418583
Participants:34
Impact:96.9% (experimental) vs 97.96% (control); no significant difference
Trust score:4/5

palatal bony window area reduction

1 evidences

Adding type‑1 collagen particles plus i‑PRF to periapical surgery did not improve bone‑defect healing compared with surgery alone; both groups showed large lesion reductions at 12 months.

Trust comment: Randomized controlled trial, registered and followed 12‑month radiographic endpoints; moderate sample size limits precision.

Study Details

PMID:37418583
Participants:34
Impact:99.03% (experimental) vs 100% (control); no significant difference
Trust score:4/5

complete closure of through‑and‑through bony window

1 evidences

Adding type‑1 collagen particles plus i‑PRF to periapical surgery did not improve bone‑defect healing compared with surgery alone; both groups showed large lesion reductions at 12 months.

Trust comment: Randomized controlled trial, registered and followed 12‑month radiographic endpoints; moderate sample size limits precision.

Study Details

PMID:37418583
Participants:34
Impact:14 cases total (7 experimental, 7 control); no between‑group difference
Trust score:4/5

3D tissue thickness change (S0–S2)

1 evidences

Porcine collagen matrix (CM) and free gingival graft (FGG) produced comparable 3D tissue thickness changes, but FGG yielded larger gains in keratinized tissue width; CM had less analgesic use and shorter surgical time.

Trust comment: Randomized controlled clinical study with objective volumetric measures and adequate follow‑up, but modest sample and some baseline/timing heterogeneity.

Study Details

PMID:37326686
Participants:32
Impact:CM −0.04 ± 0.40 mm (patient‑level) vs FGG −0.13 ± 0.23 mm; patient‑level difference not significant (p=0.467)
Trust score:4/5

keratinized tissue (KT) width gain at 6 months

1 evidences

Porcine collagen matrix (CM) and free gingival graft (FGG) produced comparable 3D tissue thickness changes, but FGG yielded larger gains in keratinized tissue width; CM had less analgesic use and shorter surgical time.

Trust comment: Randomized controlled clinical study with objective volumetric measures and adequate follow‑up, but modest sample and some baseline/timing heterogeneity.

Study Details

PMID:37326686
Participants:32
Impact:FGG +4.41 ± 1.31 mm vs CM +1.47 ± 1.25 mm (implant‑level); FGG > CM, significant
Trust score:4/5

postoperative analgesic use

1 evidences

Porcine collagen matrix (CM) and free gingival graft (FGG) produced comparable 3D tissue thickness changes, but FGG yielded larger gains in keratinized tissue width; CM had less analgesic use and shorter surgical time.

Trust comment: Randomized controlled clinical study with objective volumetric measures and adequate follow‑up, but modest sample and some baseline/timing heterogeneity.

Study Details

PMID:37326686
Participants:32
Impact:CM 1.20 ± 1.08 tablets vs FGG 5.65 ± 6.39 tablets (CM lower, p=0.001)
Trust score:4/5

crestal mucosal thickness gain (120 days)

1 evidences

Collagen matrix (VCMX) produced similar buccal volume gains and better patient‑reported outcomes (less pain) but failed to demonstrate non‑inferiority to connective tissue graft (SCTG) for crestal mucosal thickness at the primary endpoint.

Trust comment: Multicenter RCT with reasonable sample and follow‑up; primary non‑inferiority endpoint not met but PROMs robustly reported.

Study Details

PMID:37403575
Participants:79
Impact:VCMX 0.3 ± 2.1 mm vs SCTG 0.8 ± 1.6 mm (p=0.455); non‑inferiority not shown
Trust score:4/5

buccal mucosal thickness gain

1 evidences

Collagen matrix (VCMX) produced similar buccal volume gains and better patient‑reported outcomes (less pain) but failed to demonstrate non‑inferiority to connective tissue graft (SCTG) for crestal mucosal thickness at the primary endpoint.

Trust comment: Multicenter RCT with reasonable sample and follow‑up; primary non‑inferiority endpoint not met but PROMs robustly reported.

Study Details

PMID:37403575
Participants:79
Impact:VCMX 0.9 ± 2.0 mm vs SCTG 1.1 ± 1.4 mm (p=0.431); no significant difference
Trust score:4/5

patient‑reported outcomes (PROMs), including pain

1 evidences

Collagen matrix (VCMX) produced similar buccal volume gains and better patient‑reported outcomes (less pain) but failed to demonstrate non‑inferiority to connective tissue graft (SCTG) for crestal mucosal thickness at the primary endpoint.

Trust comment: Multicenter RCT with reasonable sample and follow‑up; primary non‑inferiority endpoint not met but PROMs robustly reported.

Study Details

PMID:37403575
Participants:79
Impact:PROMs favored VCMX (less pain); reported as statistically favorable
Trust score:4/5

probing depth (PD) reduction

4 evidences

Use of a collagen membrane with bovine bone graft improved periodontal pocket depth and attachment over 12 months compared with flap procedure alone.

Trust comment: Prospective randomized controlled clinical trial with 12-month follow-up; moderate sample size and clinically relevant endpoints.

Study Details

PMID:15367197
Participants:34
Impact:-5.08 mm (collagen-BBM group, 12 months)
Trust score:4/5

Both access flap alone and access flap with xenograft plus collagen membrane produced similar clinical improvements at 12 months; no significant advantage from adding GBR/collagen membrane.

Trust comment: Randomized controlled trial with full 12‑month completion and blinded examiners; moderate sample size and both arms received systemic antimicrobials.

Study Details

PMID:37382408
Participants:40
Impact:Control −4.2 ± 1.8 mm vs Test −3.7 ± 1.9 mm; both improved, no significant difference
Trust score:4/5

L-PRF+IBB was non-inferior to collagen membrane+IBB for clinical attachment gain and produced less gingival recession, though it had slightly less probing-depth reduction.

Trust comment: Randomized non-inferiority trial with balanced groups and 12-month follow-up; results reported with CIs.

Study Details

PMID:33547808
Participants:62
Impact:-0.499 mm (CM+IBB - L-PRF+IBB = 0.499 mm; L-PRF+IBB had ~0.499 mm less PD reduction)
Trust score:4/5

In periodontal defects, GTR using collagen membranes and autogenous periosteal+bone chip treatment both improved probing depth, attachment level, and bone defect fill more than debridement alone; autogenous periosteal approach gave greatest bone gain.

Trust comment: Randomized controlled clinical trial with objective surgical re-entry measurements and clear numerical outcomes; directly evaluates collagen membranes.

Study Details

PMID:20583915
Participants:42
Impact:GTR: 5.2 mm; aCPRT: 4.4 mm; OFD: 2.9 mm (1 year)
Trust score:4/5

marginal bone level (MBL) gain

1 evidences

Both access flap alone and access flap with xenograft plus collagen membrane produced similar clinical improvements at 12 months; no significant advantage from adding GBR/collagen membrane.

Trust comment: Randomized controlled trial with full 12‑month completion and blinded examiners; moderate sample size and both arms received systemic antimicrobials.

Study Details

PMID:37382408
Participants:40
Impact:Control +1.7 ± 1.6 mm vs Test +2.4 ± 1.4 mm; no significant difference
Trust score:4/5

absence of bleeding/suppuration on probing

1 evidences

Both access flap alone and access flap with xenograft plus collagen membrane produced similar clinical improvements at 12 months; no significant advantage from adding GBR/collagen membrane.

Trust comment: Randomized controlled trial with full 12‑month completion and blinded examiners; moderate sample size and both arms received systemic antimicrobials.

Study Details

PMID:37382408
Participants:40
Impact:60% implants (both groups) achieved absence of BOP & SOP
Trust score:4/5

proportion of small peptide oligomers after digestion

1 evidences

Daily 5 g collagen peptides enriched in Hyp‑containing motifs for 42 days increased skin elasticity versus normal collagen hydrolysate and showed higher small‑peptide fraction and cellular uptake in digestion/transport models.

Trust comment: Randomized double‑blind design but small sample (n=30) limits generalizability; mechanistic in vitro data support absorption claims.

Study Details

PMID:37970760
Participants:30
Impact:CP product ≈70% <500 Da vs control ≈50% after digestion (LC‑MS)
Trust score:3/5

cellular peptide uptake

1 evidences

Daily 5 g collagen peptides enriched in Hyp‑containing motifs for 42 days increased skin elasticity versus normal collagen hydrolysate and showed higher small‑peptide fraction and cellular uptake in digestion/transport models.

Trust comment: Randomized double‑blind design but small sample (n=30) limits generalizability; mechanistic in vitro data support absorption claims.

Study Details

PMID:37970760
Participants:30
Impact:Uptake ~27% (CP) vs ~21% (control) in transport models
Trust score:3/5

wrinkle depth and height

1 evidences

Daily low‑molecular‑weight collagen peptide (1,650 mg/day) for 8 weeks improved wrinkles, skin elasticity, hydration, dermal density, pore metrics and reduced sebum versus placebo, with sustained effects after washout and no adverse events.

Trust comment: Well‑designed randomized, double‑blind, placebo‑controlled trial with adequate sample size, comprehensive validated measures and high compliance.

Study Details

PMID:40935395
Participants:70
Impact:Significant reductions in maximum and average depth at crow’s feet, nasolabial folds and neck versus placebo (p<0.05)
Trust score:5/5

skin elasticity (R2, R5, R7)

2 evidences

Daily low‑molecular‑weight collagen peptide (1,650 mg/day) for 8 weeks improved wrinkles, skin elasticity, hydration, dermal density, pore metrics and reduced sebum versus placebo, with sustained effects after washout and no adverse events.

Trust comment: Well‑designed randomized, double‑blind, placebo‑controlled trial with adequate sample size, comprehensive validated measures and high compliance.

Study Details

PMID:40935395
Participants:70
Impact:Significant increases from baseline and versus placebo at day 10, week 4, week 8 and 2 weeks post‑intake
Trust score:5/5

A 12-week within-subject controlled clinical trial (one eye treated, the other as control) found the eye cream containing RFF, N-acetylneuraminic acid and peptides increased periorbital hydration, collagen density and skin elasticity with high participant satisfaction and no adverse effects.

Trust comment: Randomized, within-subject controlled 12-week trial with objective measures (n=37); small sample and product provided by company limit generalizability.

Study Details

PMID:38932444
Participants:37
Impact:R2 +14.1%, R5 +20.9%, R7 +28.1% (12 weeks)
Trust score:3/5

skin hydration and density

1 evidences

Daily low‑molecular‑weight collagen peptide (1,650 mg/day) for 8 weeks improved wrinkles, skin elasticity, hydration, dermal density, pore metrics and reduced sebum versus placebo, with sustained effects after washout and no adverse events.

Trust comment: Well‑designed randomized, double‑blind, placebo‑controlled trial with adequate sample size, comprehensive validated measures and high compliance.

Study Details

PMID:40935395
Participants:70
Impact:Inner and surface hydration and dermal density improved significantly versus placebo and effects persisted 2 weeks post‑intake
Trust score:5/5

patellar tendon stiffness

1 evidences

Daily 5 g specific collagen peptides during 14 weeks of high-load resistance training increased patellar tendon cross-sectional area (hypertrophy) versus placebo; tendon stiffness, muscle CSA and strength improved with training but were not affected by supplementation.

Trust comment: Randomized, placebo-controlled trial (n=50 healthy males) with objective structural outcomes (imaging), moderate sample size and clear intervention.

Study Details

PMID:37424319
Participants:50
Impact:increased with training but no additional effect of supplementation
Trust score:4/5

skin brightness

1 evidences

Daily intake of a fish-collagen + Djulis drink for 8 weeks produced measurable improvements in multiple skin appearance and hydration measures versus placebo.

Trust comment: Randomized double-blind placebo-controlled trial with 50 subjects and reported objective percent changes, though full methodological details (e.g., dropout, measurement methods) are limited in summary text.

Study Details

PMID:32530124
Participants:50
Impact:+5.4% (8 weeks)
Trust score:4/5

crow's feet

1 evidences

Daily intake of a fish-collagen + Djulis drink for 8 weeks produced measurable improvements in multiple skin appearance and hydration measures versus placebo.

Trust comment: Randomized double-blind placebo-controlled trial with 50 subjects and reported objective percent changes, though full methodological details (e.g., dropout, measurement methods) are limited in summary text.

Study Details

PMID:32530124
Participants:50
Impact:+14.9% (8 weeks)
Trust score:4/5

skin texture

2 evidences

A 90-day randomized trial found that ortho-silicic acid stabilized by hydrolyzed marine collagen improved skin firmness, hydration, and texture by clinical assessment.

Trust comment: Randomized, placebo-controlled trial but small sample (n=22) and objective imaging did not show statistical differences.

Study Details

PMID:28941141
Participants:22
Impact:improved (clinical evaluation statistically superior to placebo)
Trust score:3/5

Daily intake of a fish-collagen + Djulis drink for 8 weeks produced measurable improvements in multiple skin appearance and hydration measures versus placebo.

Trust comment: Randomized double-blind placebo-controlled trial with 50 subjects and reported objective percent changes, though full methodological details (e.g., dropout, measurement methods) are limited in summary text.

Study Details

PMID:32530124
Participants:50
Impact:+9.9% (8 weeks)
Trust score:4/5

wrinkles

1 evidences

Daily intake of a fish-collagen + Djulis drink for 8 weeks produced measurable improvements in multiple skin appearance and hydration measures versus placebo.

Trust comment: Randomized double-blind placebo-controlled trial with 50 subjects and reported objective percent changes, though full methodological details (e.g., dropout, measurement methods) are limited in summary text.

Study Details

PMID:32530124
Participants:50
Impact:+29.3% (8 weeks)
Trust score:4/5

polyphasic potentials (orbicularis oculi and oris)

1 evidences

In patients with long-standing facial palsy, adding in-situ collagen injections to rehabilitative therapy improved some electromyographic measures and patient-reported disease perception versus rehab alone.

Trust comment: Randomized controlled pilot with clinically relevant EMG and questionnaire outcomes but small sample and short follow-up limit strength of inference.

Study Details

PMID:32667151
Participants:40
Impact:reduced vs control (significant; P=0.017 and P=0.015)
Trust score:3/5

duration of voluntary muscle activity (orbicularis oris)

1 evidences

In patients with long-standing facial palsy, adding in-situ collagen injections to rehabilitative therapy improved some electromyographic measures and patient-reported disease perception versus rehab alone.

Trust comment: Randomized controlled pilot with clinically relevant EMG and questionnaire outcomes but small sample and short follow-up limit strength of inference.

Study Details

PMID:32667151
Participants:40
Impact:increased vs control (significant; P=0.018)
Trust score:3/5

patient disease perception (FDI questionnaire)

1 evidences

In patients with long-standing facial palsy, adding in-situ collagen injections to rehabilitative therapy improved some electromyographic measures and patient-reported disease perception versus rehab alone.

Trust comment: Randomized controlled pilot with clinically relevant EMG and questionnaire outcomes but small sample and short follow-up limit strength of inference.

Study Details

PMID:32667151
Participants:40
Impact:improved questionnaire subscores vs control
Trust score:3/5

clinical response in RA

1 evidences

Twelve weeks of low-dose oral bovine type II collagen did not produce a statistically significant improvement in early rheumatoid arthritis vs placebo, though numerically more responders occurred in collagen groups.

Trust comment: Double-blind randomized trial with moderate sample size but negative primary outcome and notable withdrawals, limiting evidence for efficacy.

Study Details

PMID:8546737
Participants:90
Impact:no significant difference between groups; responder counts: 10 mg:7, 1 mg:6, placebo:4
Trust score:3/5

patellar tendon cross-sectional area (CSA)

2 evidences

Daily 5 g specific collagen peptides during 14 weeks of high-load resistance training increased patellar tendon cross-sectional area (hypertrophy) versus placebo; tendon stiffness, muscle CSA and strength improved with training but were not affected by supplementation.

Trust comment: Randomized, placebo-controlled trial (n=50 healthy males) with objective structural outcomes (imaging), moderate sample size and clear intervention.

Study Details

PMID:37424319
Participants:50
Impact:significantly greater increase vs placebo (supplementation × training) (statistically significant)
Trust score:4/5

In older adults, 12 months heavy resistance training increased patellar tendon stiffness and preserved material properties compared with moderate/no training; tendon cross-sectional area increased with both training loads, but collagen content and cross-links did not change.

Trust comment: Well-characterized randomized nested sub-study with rigorous mechanical, imaging, biopsy and biochemical measures and adequate completion (n=33).

Study Details

PMID:30704412
Participants:33
Impact:increased after HRT (+6%) and MRT (+5%)
Trust score:5/5

rectus femoris CSA and maximal voluntary knee extension strength

1 evidences

Daily 5 g specific collagen peptides during 14 weeks of high-load resistance training increased patellar tendon cross-sectional area (hypertrophy) versus placebo; tendon stiffness, muscle CSA and strength improved with training but were not affected by supplementation.

Trust comment: Randomized, placebo-controlled trial (n=50 healthy males) with objective structural outcomes (imaging), moderate sample size and clear intervention.

Study Details

PMID:37424319
Participants:50
Impact:increased due to training independently of supplementation (no supplement effect)
Trust score:4/5

complete wound healing rate

2 evidences

Topical fish collagen gel applied to periwound skin (12 weeks) produced higher healing rates, larger quality-of-life gains, and slightly greater pain reduction than placebo, though many between-group differences were not statistically significant.

Trust comment: Randomized single-center trial with 100 enrolled and 92 completers, using objective wound measures and validated PRO instruments though some between-group differences lacked statistical significance.

Study Details

PMID:35742357
Participants:92
Impact:12 weeks: 27.7% vs 24.4% (collagen vs placebo); 24 weeks: 53.2% vs 40% (collagen vs placebo) — higher with collagen but not statistically significant overall
Trust score:4/5

Multicenter randomized trial comparing a living skin-equivalent (Graftskin, a collagen-containing product) versus moist gauze for chronic diabetic foot ulcers; assessed healing at 12 weeks.

Trust comment: Randomized multicenter clinical trial with intention-to-treat analysis showing significant benefit; product contains collagen matrix so findings are relevant to collagen-based therapy.

Study Details

PMID:11213881
Participants:208
Impact:+18 percentage points (56% Graftskin vs 38% control at 12 weeks; P=0.0042)
Trust score:4/5

quality of life (Skindex-29, CIVIQ)

1 evidences

Topical fish collagen gel applied to periwound skin (12 weeks) produced higher healing rates, larger quality-of-life gains, and slightly greater pain reduction than placebo, though many between-group differences were not statistically significant.

Trust comment: Randomized single-center trial with 100 enrolled and 92 completers, using objective wound measures and validated PRO instruments though some between-group differences lacked statistical significance.

Study Details

PMID:35742357
Participants:92
Impact:Skindex-29 increase 17% vs 7.75% at 12 wk (collagen vs placebo); CIVIQ increase 17.6% vs 9.1% at 12 wk (collagen vs placebo); greater improvement with collagen
Trust score:4/5

pain intensity (NRS)

2 evidences

Collagen injections (alone or with PRP) and PRP alone all improved pain and function over time, with no clear advantage of collagen over PRP or combined therapy at 24 weeks.

Trust comment: Randomized controlled trial with validated clinical and imaging outcomes; open-label and moderate sample size limit certainty.

Study Details

PMID:36536333
Participants:82
Impact:within-group reduction (p<0.001); no difference vs PRP/combined (p=0.870)
Trust score:4/5

Topical fish collagen gel applied to periwound skin (12 weeks) produced higher healing rates, larger quality-of-life gains, and slightly greater pain reduction than placebo, though many between-group differences were not statistically significant.

Trust comment: Randomized single-center trial with 100 enrolled and 92 completers, using objective wound measures and validated PRO instruments though some between-group differences lacked statistical significance.

Study Details

PMID:35742357
Participants:92
Impact:mean decrease at 12 wk: −3.07 points (collagen) vs −2.49 points (placebo); pain decreased in both groups with larger reduction in collagen group
Trust score:4/5

pain (VNRS)

1 evidences

Combined UC-II and hydrolysed collagen (daily) for 12 weeks produced improvements in pain and function similar to placebo; no significant between-group differences were observed.

Trust comment: Well-conducted randomized double-blind placebo-controlled trial (n=68) with validated outcomes but relatively short duration and limited power to detect small effects.

Study Details

PMID:40897777
Participants:68
Impact:mean reduction at 12 weeks: collagen −2.21 points vs control −2.29 points; between-group difference 0.08 (not significant)
Trust score:4/5

knee function (KOOS subscales)

1 evidences

Combined UC-II and hydrolysed collagen (daily) for 12 weeks produced improvements in pain and function similar to placebo; no significant between-group differences were observed.

Trust comment: Well-conducted randomized double-blind placebo-controlled trial (n=68) with validated outcomes but relatively short duration and limited power to detect small effects.

Study Details

PMID:40897777
Participants:68
Impact:improved over time in both groups with no significant between-group differences
Trust score:4/5

rescue medication consumption

1 evidences

Combined UC-II and hydrolysed collagen (daily) for 12 weeks produced improvements in pain and function similar to placebo; no significant between-group differences were observed.

Trust comment: Well-conducted randomized double-blind placebo-controlled trial (n=68) with validated outcomes but relatively short duration and limited power to detect small effects.

Study Details

PMID:40897777
Participants:68
Impact:decreased over time in both groups with no significant between-group differences
Trust score:4/5

Pain (VAS)

12 evidences

Stentoplasty using resorbable calcium-salt bone fillers in older adults with a single vertebral compression fracture reduced pain and disability and promoted bone formation over 3 years, with slight early loss of restored vertebral height.

Trust comment: Prospective randomized human trial with 3-year follow-up and objective radiological measures, but modest sample size (42) limits generalizability.

Study Details

PMID:34040361
Participants:42
Impact:Group B (HAP/COL) VAS decreased from 7.71 to 1.86 post-op (−5.85 points)
Trust score:4/5

In athletes with early knee arthritis, 12 weeks of collagen supplementation reduced pain from baseline but was not superior to exercise; combined collagen+exercise improved several functional outcomes.

Trust comment: Quasi‑randomized, blinded trial with modest sample size and short (12‑week) collagen exposure limiting long‑term conclusions.

Study Details

PMID:38063519
Participants:48
Impact:significant reduction from baseline in all groups over 12 weeks (p<0.001); no between-group differences
Trust score:3/5

A 6-month randomized trial found the product containing undenatured type II collagen (Artneo) improved pain, stiffness, and some MRI signs of synovitis and was not inferior to glucosamine+chondroitin.

Trust comment: Randomized clinical trial directly testing an undenatured type II collagen-containing product but small sample (n=70) and limited power; moderate confidence.

Study Details

PMID:38785054
Participants:70
Impact:decreased in both groups (no between-group difference)
Trust score:3/5

Adding leukocyte- and platelet-rich fibrin (with or without occlusive membrane including collagen membrane stratum) to root-end surgery did not improve patient-reported pain, symptoms, activity impairment, or medication use in the first postoperative week.

Trust comment: Randomized controlled trial with 50 patients but open design and short subjective follow-up period.

Study Details

PMID:29524025
Participants:50
Impact:No significant difference between LPRF and control over 7 days
Trust score:3/5

Randomized, double-blind 24-week pilot trial in knee OA patients comparing HC-II (type II collagen hydrolysate), EC-HC-II (chicken essence + HC-II), glucosamine, and placebo; HC-II reduced early pain and EC-HC-II increased fat-free mass and grip strength versus some comparators.

Trust comment: Randomized, double-blind human trial directly testing type II collagen hydrolysate; pilot study with moderate sample size and some endpoints lacking detailed effect sizes.

Study Details

PMID:36918892
Participants:151
Impact:HC-II: -0.9 ± 1.89 at day 14 (p=0.034); HC-II vs placebo LSM difference -1.3 (95% CI -2.51, -0.13), p=0.021
Trust score:4/5

A single intra-articular injection of type I atelocollagen reduced knee pain (VAS) more than saline at 24 weeks; functional scores (WOMAC, SF-36) improved from baseline but differences versus placebo were not significant.

Trust comment: Large double-blind randomized trial (n=200) with 24-week follow-up showing a significant VAS pain benefit but limited functional between-group effects.

Study Details

PMID:31370668
Participants:200
Impact:significantly better improvement at 24 weeks in BioCollagen vs placebo; higher proportions achieving >20% and >40% VAS improvements
Trust score:4/5

Multicenter double-blind randomized trial (stage III knee OA subgroup) showing undenatured type II chicken collagen (NK2/Artneo) improved pain, stiffness, function and quality of life vs placebo over 180 days.

Trust comment: Multicenter double-blind randomized placebo-controlled trial but subgroup sample is small (n=50), supporting moderate-to-high confidence.

Study Details

PMID:40237733
Participants:50
Impact:reduced with Artneo vs placebo (statistically significant)
Trust score:4/5

Intra-articular porcine-collagen product (MD-Knee) was non-inferior to sodium hyaluronate in improving function and pain in knee osteoarthritis up to 6 months.

Trust comment: Double-blind, randomized, active-controlled multicenter trial (64 enrolled, ~60 completers) with appropriate endpoints; no placebo arm and follow-up limited to 6 months.

Study Details

PMID:26905565
Participants:60
Impact:reduced in both groups; no significant difference between treatments
Trust score:4/5

Adding native/hydrolyzed collagen to a combo of CS/GL/MSM/HA produced larger pain reductions and better function than the same regimen without collagen in knee OA exacerbations.

Trust comment: Randomized single-center phase IV study with small sample size providing positive signals but limited generalizability.

Study Details

PMID:40561485
Participants:60
Impact:Reduced −74% with collagen vs −56% without (p=0.04)
Trust score:3/5

Oral chicken type II collagen (0.1 mg/day) reduced pain, stiffness and joint counts in RA patients but was less effective than methotrexate and had fewer/milder side effects.

Trust comment: Large multicenter randomized double-blind phase III trial with active comparator (MTX); good design though NSAID co-therapy and some dropouts limit interpretation.

Study Details

PMID:19951408
Participants:454
Impact:Decreased from 6.02 to 3.58 at 24 weeks (−40.5% absolute change)
Trust score:4/5

Randomized double-blind 30-day trial (67 completers) found Aflapin reduced knee pain and improved function; collagen type II cleavage biomarker (C2C) and inflammatory biomarkers decreased.

Trust comment: Randomized, double-blind, placebo-controlled trial with objective biomarker and clinical endpoints but small, short-duration study.

Study Details

PMID:35512759
Participants:67
Impact:−45% vs baseline (Aflapin group) (significant vs placebo)
Trust score:4/5

Adding i-PRF to autogenous demineralized dentin graft did not change alveolar ridge width loss but reduced patient-reported pain and better preserved keratinized tissue at 6 months.

Trust comment: Randomized clinical trial with objective radiographic and histologic outcomes; modest sample size and partial blinding.

Study Details

PMID:39429193
Participants:22
Impact:lower with i-PRF (mean 2.18 vs 3.82; p=0.012)
Trust score:4/5

function and quality of life (WOMAC, SF-36)

1 evidences

A single intra-articular injection of type I atelocollagen reduced knee pain (VAS) more than saline at 24 weeks; functional scores (WOMAC, SF-36) improved from baseline but differences versus placebo were not significant.

Trust comment: Large double-blind randomized trial (n=200) with 24-week follow-up showing a significant VAS pain benefit but limited functional between-group effects.

Study Details

PMID:31370668
Participants:200
Impact:improved from baseline after injection but no significant between-group differences
Trust score:4/5

mean root coverage (MRC)

2 evidences

Adding rhPDGF to a porcine cross-linked collagen matrix improved root coverage, gingival thickness and aesthetic scores at 6 months versus collagen matrix with saline.

Trust comment: Triple-blinded, randomized, placebo-controlled human trial with complete follow-up and appropriate statistical models, high internal validity.

Study Details

PMID:35871600
Participants:30
Impact:+10.5 percentage points (88.25% vs 77.72%)
Trust score:5/5

Adding cross-linked hyaluronic acid to connective tissue grafts did not change root coverage but increased elastic fibers and produced a modest (non-significant) increase in collagen density.

Trust comment: Randomized split-mouth RCT with histologic and clinical endpoints but small sample and primary intervention was hyaluronic acid rather than a collagen product.

Study Details

PMID:38808976
Participants:24
Impact:84.32%±34.46% (test) vs 85.71%±36.43% (control); no significant difference (p=0.991)
Trust score:3/5

longer-term muscle protein synthesis (MPS)

1 evidences

In older women, collagen peptide supplementation (30 g twice daily for 6 days) did not increase longer-term muscle protein synthesis (MPS), whereas whey protein did; collagen produced only a small acute MPS increase with exercise.

Trust comment: Small, tightly controlled isotope tracer RCT (n=22) with high internal validity for metabolic outcomes but limited generalizability due to sample size and female-only cohort.

Study Details

PMID:31919527
Participants:22
Impact:Whey protein: +0.063%/d (Rest) and +0.173%/d (Exercise); Collagen peptides: not significantly elevated (Rest +0.011%/d; Exercise +0.020%/d)
Trust score:4/5

acute MPS response

1 evidences

In older women, collagen peptide supplementation (30 g twice daily for 6 days) did not increase longer-term muscle protein synthesis (MPS), whereas whey protein did; collagen produced only a small acute MPS increase with exercise.

Trust comment: Small, tightly controlled isotope tracer RCT (n=22) with high internal validity for metabolic outcomes but limited generalizability due to sample size and female-only cohort.

Study Details

PMID:31919527
Participants:22
Impact:Whey protein increased acute MPS (Rest +0.017%/h; Exercise +0.032%/h); Collagen increased acute MPS only with exercise (+0.012%/h) and less than whey
Trust score:4/5

buccal soft tissue profile increase (BSP)

3 evidences

Compared connective tissue graft (CTG) versus a collagen matrix (CMX) at single implant sites; CTG produced greater long-term buccal soft tissue gain and less bone loss.

Trust comment: Multi-centre randomized controlled trial with objective digital measurements and moderate follow-up loss (50/60 at 3 years).

Study Details

PMID:38485651
Participants:50
Impact:CTG +0.83 mm; CMX +0.48 mm; mean diff +0.35 mm (CTG>CMX)
Trust score:4/5

At 1 year CTG produced greater buccal soft tissue increase and less graft shrinkage and marginal bone loss than collagen matrix (CMX).

Trust comment: Multi-centre RCT with objective digital measurements at 1 year and appropriate statistical reporting.

Study Details

PMID:35781692
Participants:60
Impact:CTG +0.98 mm vs CMX +0.57 mm; mean diff +0.41 mm (CTG>CMX)
Trust score:4/5

At 3 months CTG produced numerically larger buccal soft tissue gains than CMX with some measures of worse peri-implant bone and recession for CMX.

Trust comment: Multi-centre RCT with short-term 3-month outcomes and objective digital measures; borderline statistical significance for primary endpoint.

Study Details

PMID:34605057
Participants:60
Impact:CTG +1.15 mm vs CMX +0.85 mm; mean diff +0.30 mm (borderline significance, p=0.054)
Trust score:4/5

marginal bone loss

5 evidences

At 1 year CTG produced greater buccal soft tissue increase and less graft shrinkage and marginal bone loss than collagen matrix (CMX).

Trust comment: Multi-centre RCT with objective digital measurements at 1 year and appropriate statistical reporting.

Study Details

PMID:35781692
Participants:60
Impact:CMX resulted in ~0.39 mm more marginal bone loss than CTG
Trust score:4/5

Compared connective tissue graft (CTG) versus a collagen matrix (CMX) at single implant sites; CTG produced greater long-term buccal soft tissue gain and less bone loss.

Trust comment: Multi-centre randomized controlled trial with objective digital measurements and moderate follow-up loss (50/60 at 3 years).

Study Details

PMID:38485651
Participants:50
Impact:CMX −0.43 mm more than CTG
Trust score:4/5

Randomized study of immediate molar implants using autologous bone chips, a collagen membrane (Ossix), or both; after 12 months all groups had similar modest marginal bone loss.

Trust comment: Randomized prospective design with clinical and radiographic endpoints; moderate follow-up losses but relevant use of a collagen membrane.

Study Details

PMID:22117841
Participants:76
Impact:Average bone loss 0.48 mm at 12 months (no significant differences among groups)
Trust score:4/5

At 3 months CTG produced numerically larger buccal soft tissue gains than CMX with some measures of worse peri-implant bone and recession for CMX.

Trust comment: Multi-centre RCT with short-term 3-month outcomes and objective digital measures; borderline statistical significance for primary endpoint.

Study Details

PMID:34605057
Participants:60
Impact:CMX ~0.38 mm more than CTG
Trust score:4/5

At 12 months both transcrestal and lateral sinus floor elevation (latter with a resorbable collagen membrane) achieved near-complete radiographic implant embedding and minimal marginal bone loss.

Trust comment: Bi-center randomized trial with objective radiographic endpoints and one-year follow-up.

Study Details

PMID:31240743
Participants:54
Impact:minimal (≤1 mm) at 12 months
Trust score:4/5

patient aesthetic satisfaction

1 evidences

Compared connective tissue graft (CTG) versus a collagen matrix (CMX) at single implant sites; CTG produced greater long-term buccal soft tissue gain and less bone loss.

Trust comment: Multi-centre randomized controlled trial with objective digital measurements and moderate follow-up loss (50/60 at 3 years).

Study Details

PMID:38485651
Participants:50
Impact:no significant difference between groups
Trust score:4/5

implant/suprastructure survival

1 evidences

Tested Bio-Oss Collagen versus no grafting during sinus floor elevation; after 1 year there were no differences in implant survival, bone loss or patient-reported outcomes.

Trust comment: Single-blind randomized controlled trial with 1-year follow-up and complete reporting of key clinical and PROM outcomes.

Study Details

PMID:36639342
Participants:40
Impact:100% survival in both groups
Trust score:4/5

peri-implant marginal bone loss

2 evidences

22 patients received vertical bone augmentation with either resorbable collagen barriers or nonresorbable barriers; both showed minimal and similar bone loss at 3 years.

Trust comment: Randomized controlled trial with blinded assessors and 3-year follow-up but small sample size (n=22).

Study Details

PMID:20657877
Participants:22
Impact:Resorbable collagen barriers mean loss 0.55 mm; nonresorbable mean loss 0.53 mm at 3 years
Trust score:4/5

Tested Bio-Oss Collagen versus no grafting during sinus floor elevation; after 1 year there were no differences in implant survival, bone loss or patient-reported outcomes.

Trust comment: Single-blind randomized controlled trial with 1-year follow-up and complete reporting of key clinical and PROM outcomes.

Study Details

PMID:36639342
Participants:40
Impact:no significant difference between groups
Trust score:4/5

patient-reported outcomes (OHRQoL, satisfaction)

1 evidences

Tested Bio-Oss Collagen versus no grafting during sinus floor elevation; after 1 year there were no differences in implant survival, bone loss or patient-reported outcomes.

Trust comment: Single-blind randomized controlled trial with 1-year follow-up and complete reporting of key clinical and PROM outcomes.

Study Details

PMID:36639342
Participants:40
Impact:both groups showed significant improvement; no between-group difference
Trust score:4/5

complete ulcer healing within 8 weeks

1 evidences

Compared topical collagen dressings to hydrocolloid for pressure ulcers over 8 weeks and found similar healing rates and times; collagen was more expensive.

Trust comment: Randomized, single-blind trial with clear outcomes and reasonable sample size for wound-healing endpoints.

Study Details

PMID:12558709
Participants:65
Impact:Collagen 51% vs Hydrocolloid 50% (difference +1%)
Trust score:4/5

time to heal

2 evidences

Compared topical collagen dressings to hydrocolloid for pressure ulcers over 8 weeks and found similar healing rates and times; collagen was more expensive.

Trust comment: Randomized, single-blind trial with clear outcomes and reasonable sample size for wound-healing endpoints.

Study Details

PMID:12558709
Participants:65
Impact:mean 5 weeks (collagen) vs 6 weeks (hydrocolloid)
Trust score:4/5

Randomized trial in chronic diabetic foot ulcers: a porcine-derived purified reconstituted bilayer matrix (ECM product) produced higher 12-week healing rates, faster healing, and much greater wound area reduction than standard collagen-alginate dressing.

Trust comment: Randomized controlled trial showing large effects for a collagen-containing ECM product, but small sample (n=40) and industry funding/COI limit confidence.

Study Details

PMID:35001559
Participants:40
Impact:−30 days mean (37 days vs 67 days)
Trust score:3/5

area healed per day

1 evidences

Compared topical collagen dressings to hydrocolloid for pressure ulcers over 8 weeks and found similar healing rates and times; collagen was more expensive.

Trust comment: Randomized, single-blind trial with clear outcomes and reasonable sample size for wound-healing endpoints.

Study Details

PMID:12558709
Participants:65
Impact:both ~6 mm²/day (no difference)
Trust score:4/5

soft tissue thickness gain

1 evidences

Compared subepithelial connective tissue graft (SCTG) to xenogeneic collagen matrix (XCM) for buccal soft tissue augmentation; SCTG yielded greater thickness gain while XCM reduced operation time.

Trust comment: Randomized trial with objective thickness measures and histology, but small sample (n=30).

Study Details

PMID:36029335
Participants:30
Impact:SCTG 1.55±0.11 mm vs XCM 1.18±0.11 mm (diff −0.366 mm, p=0.016 favoring SCTG)
Trust score:4/5

operation time

2 evidences

Using a resorbable collagen membrane did not reduce horizontal bone resorption; piezosurgery showed no clinical advantage over rotative instruments and took longer.

Trust comment: Randomized split-mouth clinical trial in humans with clear outcome measures and moderate sample size.

Study Details

PMID:21745325
Participants:36
Impact:conventional 11.1 min vs piezosurgery 15.1 min (conventional shorter by 4.0 min; p<.001)
Trust score:4/5

Compared subepithelial connective tissue graft (SCTG) to xenogeneic collagen matrix (XCM) for buccal soft tissue augmentation; SCTG yielded greater thickness gain while XCM reduced operation time.

Trust comment: Randomized trial with objective thickness measures and histology, but small sample (n=30).

Study Details

PMID:36029335
Participants:30
Impact:XCM ~8.4 minutes shorter than SCTG
Trust score:4/5

patient pain/quality of life

1 evidences

Compared subepithelial connective tissue graft (SCTG) to xenogeneic collagen matrix (XCM) for buccal soft tissue augmentation; SCTG yielded greater thickness gain while XCM reduced operation time.

Trust comment: Randomized trial with objective thickness measures and histology, but small sample (n=30).

Study Details

PMID:36029335
Participants:30
Impact:no significant differences between groups
Trust score:4/5

retear rate after repair

1 evidences

Adding porcine atelocollagen patch during rotator cuff repair lowered retear rates at 1 year but did not change shoulder function scores.

Trust comment: Prospective randomized trial with MRI-confirmed outcomes and clear reduction in retear rate, moderate sample size.

Study Details

PMID:38551128
Participants:55
Impact:Atelocollagen 10.3% vs Conventional 34.6% (absolute reduction ~24.3 percentage points; p=0.048)
Trust score:4/5

Constant score (function)

1 evidences

Adding porcine atelocollagen patch during rotator cuff repair lowered retear rates at 1 year but did not change shoulder function scores.

Trust comment: Prospective randomized trial with MRI-confirmed outcomes and clear reduction in retear rate, moderate sample size.

Study Details

PMID:38551128
Participants:55
Impact:no significant difference between groups
Trust score:4/5

graft shrinkage (postop to 1 year)

1 evidences

At 1 year CTG produced greater buccal soft tissue increase and less graft shrinkage and marginal bone loss than collagen matrix (CMX).

Trust comment: Multi-centre RCT with objective digital measurements at 1 year and appropriate statistical reporting.

Study Details

PMID:35781692
Participants:60
Impact:CMX showed ~0.89 mm more shrinkage than CTG
Trust score:4/5

mid-facial recession

1 evidences

At 3 months CTG produced numerically larger buccal soft tissue gains than CMX with some measures of worse peri-implant bone and recession for CMX.

Trust comment: Multi-centre RCT with short-term 3-month outcomes and objective digital measures; borderline statistical significance for primary endpoint.

Study Details

PMID:34605057
Participants:60
Impact:CMX ~0.75 mm more than CTG
Trust score:4/5

complete root coverage (CRC)

4 evidences

Porcine collagen matrix used with a tunnel technique reduced surgery time and morbidity but provided less complete root coverage than palatal connective tissue grafts; both improved gingival measures at 12 months.

Trust comment: Randomized split-mouth clinical trial with objective measurements but small sample size (22 patients).

Study Details

PMID:23627374
Participants:22
Impact:Improved vs baseline but lower with collagen matrix than connective tissue graft (statistically significant)
Trust score:4/5

Using a collagen matrix or enamel matrix with flap surgery improved gum root coverage and gingival thickness compared with flap alone.

Trust comment: Randomized, double-masked dual-center trial with clear clinical endpoints though group sizes were modest (n=17 per arm).

Study Details

PMID:28753100
Participants:68
Impact:CAF+EMD 70.59% vs CAF 23.53% (CAF+EMD significantly superior, P<0.05)
Trust score:4/5

Porcine-derived collagen matrix (PDCM) produced better root coverage and less pain/time than connective tissue grafts in smokers.

Trust comment: Randomized controlled clinical trial with clear clinical measures but small sample size (28 patients).

Study Details

PMID:36057652
Participants:28
Impact:45.06% (PDCM group reported)
Trust score:4/5

Adding rhPDGF to a porcine cross-linked collagen matrix improved root coverage, gingival thickness and aesthetic scores at 6 months versus collagen matrix with saline.

Trust comment: Triple-blinded, randomized, placebo-controlled human trial with complete follow-up and appropriate statistical models, high internal validity.

Study Details

PMID:35871600
Participants:30
Impact:+39.1 percentage points (59.57% vs 20.45%)
Trust score:5/5

gingival thickness (GT) gain

2 evidences

Adding rhPDGF to a porcine cross-linked collagen matrix improved root coverage, gingival thickness and aesthetic scores at 6 months versus collagen matrix with saline.

Trust comment: Triple-blinded, randomized, placebo-controlled human trial with complete follow-up and appropriate statistical models, high internal validity.

Study Details

PMID:35871600
Participants:30
Impact:+0.22 mm (model estimate; p=0.01)
Trust score:5/5

In a split-mouth RCT, xenogeneic collagen matrix (XCM) improved root coverage and quality of life but CTG produced greater final gingival thickness and slightly better root-coverage metrics at 18 months.

Trust comment: Split-mouth, double-blind RCT with 18-month follow-up; moderate sample size but rigorous design supports moderate-high trust.

Study Details

PMID:39536202
Participants:30
Impact:GT gain: XCM ≈ 0.27 mm; CTG ≈ 0.56 mm (CTG > XCM, intergroup difference significant)
Trust score:4/5

type I procollagen gene expression

1 evidences

Daily oral collagen oligopeptides for 84 days increased dermal ECM gene expression in vitro and was tested in a double-blind randomized trial in women; clinical hydration changes did not reach significance.

Trust comment: Double-blind randomized clinical study (n=85) combined with in vitro mechanistic work; clinical endpoints partly non-significant but molecular data supportive.

Study Details

PMID:40518844
Participants:85
Impact:increased (significant, p<0.05) in fibroblast assays
Trust score:4/5

decorin and biglycan expression

1 evidences

Daily oral collagen oligopeptides for 84 days increased dermal ECM gene expression in vitro and was tested in a double-blind randomized trial in women; clinical hydration changes did not reach significance.

Trust comment: Double-blind randomized clinical study (n=85) combined with in vitro mechanistic work; clinical endpoints partly non-significant but molecular data supportive.

Study Details

PMID:40518844
Participants:85
Impact:increased (significant, p<0.05) in fibroblast assays
Trust score:4/5

skin hydration (clinical)

1 evidences

Daily oral collagen oligopeptides for 84 days increased dermal ECM gene expression in vitro and was tested in a double-blind randomized trial in women; clinical hydration changes did not reach significance.

Trust comment: Double-blind randomized clinical study (n=85) combined with in vitro mechanistic work; clinical endpoints partly non-significant but molecular data supportive.

Study Details

PMID:40518844
Participants:85
Impact:no statistically significant improvement over placebo
Trust score:4/5

lesion size reduction (2D)

1 evidences

Periapical surgery with or without a resorbable collagen membrane produced substantial lesion size reduction at 12 months with no significant difference between groups.

Trust comment: Randomized controlled trial with 12-month imaging outcomes and 30 patients analysed; moderate sample size but appropriate assessments.

Study Details

PMID:30758848
Participants:30
Impact:control 92%±12 vs GTR 86%±14 — both significant; no between-group difference (p>0.05)
Trust score:4/5

lesion size reduction (3D)

1 evidences

Periapical surgery with or without a resorbable collagen membrane produced substantial lesion size reduction at 12 months with no significant difference between groups.

Trust comment: Randomized controlled trial with 12-month imaging outcomes and 30 patients analysed; moderate sample size but appropriate assessments.

Study Details

PMID:30758848
Participants:30
Impact:control 85%±19 vs GTR 82%±13 — both significant; no between-group difference (p>0.05)
Trust score:4/5

clinical/radiographic success rate

1 evidences

Periapical surgery with or without a resorbable collagen membrane produced substantial lesion size reduction at 12 months with no significant difference between groups.

Trust comment: Randomized controlled trial with 12-month imaging outcomes and 30 patients analysed; moderate sample size but appropriate assessments.

Study Details

PMID:30758848
Participants:30
Impact:no significant difference between groups at 12 months
Trust score:4/5

complete ulcer healing rate

1 evidences

Porcine type I collagen dressing for diabetic foot ulcers increased complete healing rate and accelerated wound healing versus foam dressing alone.

Trust comment: Prospective randomized, placebo-controlled human trial with clear clinically meaningful endpoints but single-center and small sample size.

Study Details

PMID:31536746
Participants:30
Impact:+43.9 percentage points (82.4% vs 38.5%; p=0.022)
Trust score:4/5

time to 50% size reduction (median)

1 evidences

Porcine type I collagen dressing for diabetic foot ulcers increased complete healing rate and accelerated wound healing versus foam dressing alone.

Trust comment: Prospective randomized, placebo-controlled human trial with clear clinically meaningful endpoints but single-center and small sample size.

Study Details

PMID:31536746
Participants:30
Impact:shorter: 21 vs 42 days (hazard ratio 1.94; p<0.05)
Trust score:4/5

healing velocity

1 evidences

Porcine type I collagen dressing for diabetic foot ulcers increased complete healing rate and accelerated wound healing versus foam dressing alone.

Trust comment: Prospective randomized, placebo-controlled human trial with clear clinically meaningful endpoints but single-center and small sample size.

Study Details

PMID:31536746
Participants:30
Impact:faster in collagen group (p<0.05)
Trust score:4/5

treatment success (dry 24-hour pad test at 12 months)

1 evidences

Multicenter randomized trial found collagen injections less effective than surgery for cure at 12 months but with fewer and less severe complications and similar quality-of-life.

Trust comment: Multicenter randomized trial with reasonable sample size and relevant clinical endpoints, though some post-randomization refusals occurred.

Study Details

PMID:15882720
Participants:118
Impact:collagen injections 53.1% vs surgery 72.2% (per protocol), absolute difference ≈ -19.1%
Trust score:4/5

complication frequency/severity

1 evidences

Multicenter randomized trial found collagen injections less effective than surgery for cure at 12 months but with fewer and less severe complications and similar quality-of-life.

Trust comment: Multicenter randomized trial with reasonable sample size and relevant clinical endpoints, though some post-randomization refusals occurred.

Study Details

PMID:15882720
Participants:118
Impact:fewer and less severe complications with collagen injections (36 events in 23 subjects) vs surgery (84 events in 34 subjects; P=0.03)
Trust score:4/5

quality of life / satisfaction

1 evidences

Multicenter randomized trial found collagen injections less effective than surgery for cure at 12 months but with fewer and less severe complications and similar quality-of-life.

Trust comment: Multicenter randomized trial with reasonable sample size and relevant clinical endpoints, though some post-randomization refusals occurred.

Study Details

PMID:15882720
Participants:118
Impact:similar quality-of-life; non-significantly lower satisfaction with collagen (67.2% vs 79.6%)
Trust score:4/5

defect height / bone gain

1 evidences

Randomized multicenter interim study comparing two collagen membranes for guided bone regeneration found the new membrane non-inferior to reference, with similar safety and a trend to greater bone gain and lower exposure rate.

Trust comment: Prospective multicenter randomized design with CONSORT reporting; interim small sample reduces power for some comparisons.

Study Details

PMID:27990692
Participants:47
Impact:mean bone height gain CXP 4.1±2.2 mm vs BG 3.3±2.8 mm (CXP non-inferior to BG)
Trust score:4/5

membrane exposure rate

1 evidences

Randomized multicenter interim study comparing two collagen membranes for guided bone regeneration found the new membrane non-inferior to reference, with similar safety and a trend to greater bone gain and lower exposure rate.

Trust comment: Prospective multicenter randomized design with CONSORT reporting; interim small sample reduces power for some comparisons.

Study Details

PMID:27990692
Participants:47
Impact:CXP 8.3% (2/24) vs BG 16.7% (4/24) during healing
Trust score:4/5

implant survival

5 evidences

Randomized multicenter interim study comparing two collagen membranes for guided bone regeneration found the new membrane non-inferior to reference, with similar safety and a trend to greater bone gain and lower exposure rate.

Trust comment: Prospective multicenter randomized design with CONSORT reporting; interim small sample reduces power for some comparisons.

Study Details

PMID:27990692
Participants:47
Impact:100% implant survival at reentry (6 months)
Trust score:4/5

Sealing extraction sockets with a porcine collagen matrix gave similar 1-year implant and bone outcomes as connective tissue graft, avoiding a donor site.

Trust comment: Randomized controlled trial on humans with objective CBCT/radiographic measures and complete follow-up, moderate-high quality.

Study Details

PMID:25738178
Participants:30
Impact:no failures (100% survival)
Trust score:4/5

Pilot RCT (27 patients) comparing PRF membranes versus standard DBBM plus resorbable collagen membrane for augmented sites; implant survival similar and PRF group had a slightly better peri-implant marginal bone level at 2-year follow-up.

Trust comment: Randomized pilot RCT with small sample and appropriate clinical/radiographic follow-up; limited power but direct clinical relevance to use of collagen membranes.

Study Details

PMID:33554323
Participants:27
Impact:PRF 100% (14/14) vs control 85% (11/13); not statistically significant
Trust score:3/5

Both guided bone regeneration approaches produced sufficient horizontal ridge augmentation for implants; mean horizontal bone width gains at 18 months were similar and implant survival was 100% in both groups.

Trust comment: Randomized controlled trial with radiographic follow-up and near-complete retention (39 completers); moderate sample size but robust clinical endpoints.

Study Details

PMID:30884111
Participants:39
Impact:100% survival at 18 months in both groups
Trust score:4/5

Use of a collagen membrane (Bio-Gide) in ridge augmentation did not meaningfully change marginal gingiva or marginal bone levels or implant survival during the first year.

Trust comment: Randomized clinical trial with a substantial sample (93) and standardized radiographic/clinical measures; one-year follow-up limits long-term inference.

Study Details

PMID:19040446
Participants:93
Impact:97.8% survival
Trust score:4/5

PICP level (collagen type I propeptide) and LVEF change

1 evidences

Large cohort study showing that lower serum procollagen type I C-terminal propeptide (PICP) is associated with greater left ventricular reverse remodeling and better heart-failure outcomes.

Trust comment: Large well-powered cohort with derivation and validation cohorts; observational design limits causal inference but associations are robust.

Study Details

PMID:36599551
Participants:1034
Impact:low PICP (<108.1 ng/mL) associated with enhanced LVEF improvement / LVRR (P≤0.018)
Trust score:4/5

PICP and HF-related outcomes

1 evidences

Large cohort study showing that lower serum procollagen type I C-terminal propeptide (PICP) is associated with greater left ventricular reverse remodeling and better heart-failure outcomes.

Trust comment: Large well-powered cohort with derivation and validation cohorts; observational design limits causal inference but associations are robust.

Study Details

PMID:36599551
Participants:1034
Impact:low PICP associated with lower risk of HF-related outcomes (P≤0.018)
Trust score:4/5

postoperative drainage volume

2 evidences

Collagen hemostatic sponge reduced postoperative bleeding, transfusions, and hospital stay versus gelatin sponge; topical TXA reduced bleeding more than collagen.

Trust comment: Prospective randomized controlled trial with 120 patients and objective measured outcomes; moderate quality.

Study Details

PMID:29110696
Participants:120
Impact:total drainage 232.8±98 ml vs control 301.3±110.9 ml (≈−22.7%)
Trust score:4/5

Randomized trial in post-thyroidectomy bleeding showed the oxidised regenerated cellulose–collagen hemostatic agent is non-inferior to carrier-bound fibrin sealant for hemostasis and had no safety concerns.

Trust comment: Randomized controlled design with adequate sample for non-inferiority endpoint; results directly evaluate a collagen-containing hemostatic product.

Study Details

PMID:32747306
Participants:150
Impact:ORC-Coll 68.20±44.56 mL vs CBFS 68.21±40.20 mL (non-inferior)
Trust score:4/5

hemostatic efficacy and safety

1 evidences

Randomized trial in post-thyroidectomy bleeding showed the oxidised regenerated cellulose–collagen hemostatic agent is non-inferior to carrier-bound fibrin sealant for hemostasis and had no safety concerns.

Trust comment: Randomized controlled design with adequate sample for non-inferiority endpoint; results directly evaluate a collagen-containing hemostatic product.

Study Details

PMID:32747306
Participants:150
Impact:non-inferior efficacy and no adverse events reported over 6-month follow-up
Trust score:4/5

treatment success rate

3 evidences

Adding a collagen membrane plus bone mineral resulted in more radiographic bone fill but no differences in clinical signs or patient-reported outcomes at 12 months.

Trust comment: Multicenter randomized clinical trial with objective radiographic and clinical endpoints but moderate sample size.

Study Details

PMID:34169551
Participants:66
Impact:TG 32% vs CG 21% (greater proportion in TG)
Trust score:4/5

Within-subject randomized trial in children found single-application bovine collagen dressings were safe and as effective as human amniotic membrane for superficial partial-thickness burns (healing time and scarring similar).

Trust comment: Prospective internally randomized blinded trial with within-subject control in pediatric patients; moderate sample size but clinically relevant outcomes.

Study Details

PMID:35839158
Participants:43
Impact:one-time application successful in 40/43 children (93%)
Trust score:4/5

Randomized multicenter study in patients with diabetic foot: adding Collost (collagen biomaterial) to standard therapy improved ulcer healing over 4 weeks.

Trust comment: Randomized multicenter human trial with modest sample (n=71) and short follow-up (4 weeks); results plausible but limited long-term data and limited methodological details.

Study Details

PMID:28374714
Participants:71
Impact:increased from 43% to 72% (+29 percentage points)
Trust score:3/5

time to healing

4 evidences

A protease-modulating collagen-containing dressing led to more frequent and faster healing of neuropathic diabetic foot ulcers versus standard care over 6 weeks.

Trust comment: Randomized controlled trial with clear, significant outcomes but small sample and short follow-up.

Study Details

PMID:17580028
Participants:38
Impact:Mean 23.3 ± 9.9 days (dressing) vs 40.6 ± 1.15 days (control), p < 0.01
Trust score:4/5

Within-subject randomized trial in children found single-application bovine collagen dressings were safe and as effective as human amniotic membrane for superficial partial-thickness burns (healing time and scarring similar).

Trust comment: Prospective internally randomized blinded trial with within-subject control in pediatric patients; moderate sample size but clinically relevant outcomes.

Study Details

PMID:35839158
Participants:43
Impact:median time to healing 10 days for both collagen and amniotic membrane
Trust score:4/5

EpiFix (dehydrated amnion/chorion containing collagen and growth factors) produced faster and higher rates of complete healing and lower product costs than Apligraf or standard care in diabetic foot ulcers.

Trust comment: Randomised multi‑centre trial with blinded adjudication and statistically significant results, though sample size per arm was small (n=20 each).

Study Details

PMID:25424146
Participants:60
Impact:median 13 days (EpiFix) vs 49 days (Apligraf and standard care)
Trust score:4/5

PACK-CXL added to antimicrobials did not shorten healing time but had fewer serious complications (no perforations or recurrences) than antimicrobials alone.

Trust comment: Prospective clinical trial with modest sample size; unclear randomization and some baseline differences limit strength.

Study Details

PMID:24576886
Participants:40
Impact:-6.29 days (-13.7%) (39.76 vs 46.05 days; P = 0.68)
Trust score:3/5

scar quality

1 evidences

Within-subject randomized trial in children found single-application bovine collagen dressings were safe and as effective as human amniotic membrane for superficial partial-thickness burns (healing time and scarring similar).

Trust comment: Prospective internally randomized blinded trial with within-subject control in pediatric patients; moderate sample size but clinically relevant outcomes.

Study Details

PMID:35839158
Participants:43
Impact:no significant difference in scarring between collagen and amniotic membrane
Trust score:4/5

pink esthetic score (PES)

2 evidences

Randomized clinical trial (45 patients) comparing porcine-derived collagen matrix to connective tissue graft with immediate implants; esthetic scores and clinical parameters were comparable at 1 year.

Trust comment: Randomized clinical trial with moderate sample size (45) and 12-month follow-up; methodology and outcomes relevant to clinical practice.

Study Details

PMID:35324053
Participants:45
Impact:CTG 12.9 ±1.2 vs PDCM 12.1 ±1.3 at 12 months (P = 0.507; no significant difference)
Trust score:4/5

Randomized clinical trial comparing collagen plug, demineralized bone matrix (Grafton) and particulate autogenous+DBBM (MinerOss X) with vestibular socket therapy in immediate implants; all groups had good esthetic outcomes and increased facial bone thickness, with no significant differences between groups.

Trust comment: Randomized controlled clinical trial with clear radiographic outcomes but small sample (n=24) limiting between-group comparisons.

Study Details

PMID:37658342
Participants:24
Impact:Collagen plug median PES 11.5→12.0; Grafton 11.5→11.0; MinerOss X 12.0→13.0 (within-group increases for some; intergroup differences not significant)
Trust score:3/5

bone formation marker (P1NP)

1 evidences

In 74 postmenopausal women, bisphosphonate therapy (clodronate or yearly zoledronate) reduced bone turnover markers and produced differential effects on Wnt inhibitors (transient DKK1 increases with zoledronate; delayed SOST increase with clodronate).

Trust comment: Data from participants in multicenter randomized placebo-controlled trials with standard biochemical endpoints, supporting credibility.

Study Details

PMID:25003812
Participants:74
Impact:Significant decrease during bisphosphonate treatment versus baseline and placebo
Trust score:4/5

oral health-related quality of life (OHIP-14)

1 evidences

Randomized trial in 40 patients showed similar overall patient-reported recovery and OHRQL with Bio-Oss collagen vs no grafting material, but the collagen group had slightly more days of eating/sleep disturbances and pain.

Trust comment: Randomized single-blind trial with adequate sample (n=40) and validated PROMs, though some baseline imbalances and short-term PROM focus are limitations.

Study Details

PMID:33748923
Participants:40
Impact:No significant difference between Bio-Oss collagen and no grafting material
Trust score:4/5

days with eating difficulties

1 evidences

Randomized trial in 40 patients showed similar overall patient-reported recovery and OHRQL with Bio-Oss collagen vs no grafting material, but the collagen group had slightly more days of eating/sleep disturbances and pain.

Trust comment: Randomized single-blind trial with adequate sample (n=40) and validated PROMs, though some baseline imbalances and short-term PROM focus are limitations.

Study Details

PMID:33748923
Participants:40
Impact:Bio-Oss collagen 2.1 days vs no graft 0.7 days at 1 week (P = 0.04)
Trust score:4/5

days with pain / sleep disturbances

1 evidences

Randomized trial in 40 patients showed similar overall patient-reported recovery and OHRQL with Bio-Oss collagen vs no grafting material, but the collagen group had slightly more days of eating/sleep disturbances and pain.

Trust comment: Randomized single-blind trial with adequate sample (n=40) and validated PROMs, though some baseline imbalances and short-term PROM focus are limitations.

Study Details

PMID:33748923
Participants:40
Impact:More days with pain at 1 month (3.2 vs 1.3, P = 0.02) and increased sleep disturbances in collagen group (P = 0.02)
Trust score:4/5

hemostasis success rate

1 evidences

Randomized trial in spinal surgery patients showing the collagen-based topical hemostat CollaStat was noninferior to Floseal for stopping surgical bleeding with no device-related serious adverse events.

Trust comment: Randomized controlled trial with 78 patients and clear clinical endpoints; well-powered for noninferiority but single-device comparison limits generalizability.

Study Details

PMID:34246825
Participants:78
Impact:94.87% (CollaStat) vs 97.44% (Floseal); noninferior
Trust score:4/5

time to hemostasis

7 evidences

Randomized trial of a collagen-based arterial closure device showing faster hemostasis and earlier discharge with similar complication rates.

Trust comment: Randomized controlled trial (n=304) directly tested a collagen hemostatic device with clear primary outcome differences; single good-quality RCT evidence.

Study Details

PMID:9514451
Participants:304
Impact:−16.1 min (0.9 ± 3 vs 17.0 ± 8 min; p=0.0001)
Trust score:4/5

Randomized trial in spinal surgery patients showing the collagen-based topical hemostat CollaStat was noninferior to Floseal for stopping surgical bleeding with no device-related serious adverse events.

Trust comment: Randomized controlled trial with 78 patients and clear clinical endpoints; well-powered for noninferiority but single-device comparison limits generalizability.

Study Details

PMID:34246825
Participants:78
Impact:no significant difference
Trust score:4/5

Percutaneous collagen device (VasoSeal) achieved faster hemostasis but had more minor local complications and lower technical success than mechanical compression.

Trust comment: Randomized comparative clinical study with clear outcome measures but modest sample size; moderate quality.

Study Details

PMID:12743862
Participants:57
Impact:VasoSeal: immediate hemostasis in 21/26 (~≤1.75 min); Compressar mean compression time 17.4 min
Trust score:3/5

Collagen plug (VasoSeal) after PTCA markedly shortened time to hemostasis but overall local complication rates were similar, with a possible increase in large hematomas.

Trust comment: Prospective, randomized study with adequate sample size (n=150) and clear endpoints, though rare complications had low event counts.

Study Details

PMID:9554769
Participants:150
Impact:-14.4 min (3 ±3 min vs 17.4 ±7 min) reduced with collagen plug
Trust score:4/5

Collagen plug (VasoSeal) markedly shortened time to hemostasis after PTCA versus manual compression, with similar overall local complication rates.

Trust comment: Prospective randomized study with substantial sample size (n=150); clear clinical endpoints.

Study Details

PMID:10745613
Participants:150
Impact:collagen 3 ± 3 min vs control 17.4 ± 7 min (significantly shorter)
Trust score:4/5

Using a collagen plug after catheterization shortened bleeding time and caused less pain with similar complication rates.

Trust comment: Randomized study with objective measures and duplex follow-up; moderate sample size supports findings.

Study Details

PMID:9040266
Participants:62
Impact:decrease to mean 9.6 min vs 23.6 min (−14.0 min, P=0.0001)
Trust score:4/5

A collagen-derived hemostatic gel (Floseal) produced faster hemostasis, less blood loss, and quicker return to diet than cautery in children having adenoidectomy.

Trust comment: Randomized controlled trial (n=70) showing consistent objective benefits for a collagen-derived product; nonblinded but multicenter and outcomes are objective.

Study Details

PMID:15523433
Participants:70
Impact:-8.9 minutes (0.6 vs 9.5 min; Floseal vs cautery, P < 0.001)
Trust score:4/5

adverse events

6 evidences

Replacing methotrexate with daily oral collagen type II (0.5 mg) worsened disease activity in patients with long-standing rheumatoid arthritis.

Trust comment: Randomized, double-blind comparative trial with clear clinical endpoints in 92 patients, providing moderate-high quality evidence for this intervention.

Study Details

PMID:9825751
Participants:92
Impact:no significant difference between groups during study period
Trust score:4/5

A collagen corneal shield gave worse device performance and more adverse events than a hydrogel bandage, while pain scores were similar.

Trust comment: Prospective randomized multicenter single‑masked trial with clear endpoints and substantial sample size, directly testing a collagen device.

Study Details

PMID:21183106
Participants:420
Impact:collagen shield 36.5% vs hydrogel 22.2% (higher with collagen)
Trust score:4/5

Randomized trial in spinal surgery patients showing the collagen-based topical hemostat CollaStat was noninferior to Floseal for stopping surgical bleeding with no device-related serious adverse events.

Trust comment: Randomized controlled trial with 78 patients and clear clinical endpoints; well-powered for noninferiority but single-device comparison limits generalizability.

Study Details

PMID:34246825
Participants:78
Impact:no device-related serious adverse events
Trust score:4/5

Injecting collagen into masseter trigger points reduced pain and muscle activity more than lidocaine or saline over a 2-week observation.

Trust comment: Randomized, registered single-blind RCT with objective and subjective measures; limited by small sample and short follow-up.

Study Details

PMID:29973970
Participants:43
Impact:transient pain/edema; bruising in some; no serious adverse effects
Trust score:4/5

Artecoll (PMMA microspheres + bovine collagen) produced greater and longer-lasting wrinkle augmentation and higher satisfaction than standard collagen filler with acceptable safety.

Trust comment: Large randomized multicenter trial with objective and subjective outcomes and extended follow-up, supporting robustness of findings.

Study Details

PMID:15468406
Participants:251
Impact:Fewer adverse events reported with Artecoll vs control over study period (difference not statistically significant)
Trust score:4/5

In patients with active rheumatoid arthritis, oral chicken type II collagen (CCII) was effective but less so than methotrexate (MTX) over 24 weeks and was associated with fewer and milder adverse events.

Trust comment: Large randomized, double-blind multicenter trial with good completion rate (89%); CCII was less effective than standard MTX but better tolerated.

Study Details

PMID:18576295
Participants:211
Impact:Fewer and milder adverse events with CCII vs MTX (difference significant, p<0.05)
Trust score:4/5

pocket probing depth (PD)

1 evidences

Randomized clinical trial (30 patients) comparing open flap debridement, L-PRF, and L-PRF plus collagen membrane; all groups improved clinically, and the collagen-membrane group had greater radiographic defect fill but no sustained difference in crevicular PDGF/VEGF levels.

Trust comment: Randomized clinical trial with defined outcomes and blinded assessor but small sample (n=30) limits precision.

Study Details

PMID:37667213
Participants:30
Impact:-50.6% (OFD), -50.6% (L-PRF), -54.9% (L-PRF+CM) at 6 months
Trust score:4/5

clinical attachment level (CAL)

6 evidences

12-month RCT (51 subjects) showed guided tissue regeneration with collagen membrane improved probing depth and clinical attachment versus open flap debridement, but collagen membrane increased gingival recession compared with other treatments.

Trust comment: Randomized controlled clinical trial directly testing a collagen membrane vs alternatives with 12-month follow-up; moderate-high quality evidence.

Study Details

PMID:18834243
Participants:51
Impact:greater gain with CM and CS vs OFD
Trust score:4/5

Both HA/collagen (Biostite) and bovine HA (Bio-Oss) grafts produced similar, significant improvements in pocket depth, clinical attachment, and defect fill at 12 months.

Trust comment: Randomized clinical trial with objective clinical and radiographic endpoints and 12-month follow-up but small sample size limits precision.

Study Details

PMID:15086616
Participants:24
Impact:+2.9 mm (Biostite) and +4.0 mm (Bio-Oss) gain at 12 months
Trust score:4/5

In 45 patients with bilateral impacted lower third molars, use of bovine porous bone mineral with or without a collagen membrane reduced pocket depth and gained attachment versus untreated controls over long follow‑up.

Trust comment: Randomized assignment, long follow‑up (up to 72 months) and clinically meaningful endpoints support reasonable trust, though sample size moderate (45 patients, 90 sites).

Study Details

PMID:19254122
Participants:45
Impact:significant gain with BPBM or BPBM + collagen membrane vs control at all time points
Trust score:4/5

Using a bovine bone graft plus a collagen membrane improved pocket depth and attachment in people with one intrabony periodontal defect after 1 year.

Trust comment: Randomized controlled clinical study with 1-year follow-up and clear clinical endpoints supports moderate-high trust.

Study Details

PMID:12702114
Participants:28
Impact:test: -4.0 mm (10.2 → 6.2); control: -2.1 mm (10.5 → 8.4)
Trust score:4/5

Randomized trial in periodontitis patients showed similar pocket depth and attachment gains for both barriers but greater bone fill with the collagen membrane at 6 months.

Trust comment: Randomized clinical trial but small sample (30) and short-term follow-up; results plausible and directly measured.

Study Details

PMID:20228976
Participants:30
Impact:+2.60 mm (collagen) vs +2.40 mm (PLA) from baseline
Trust score:3/5

Randomized clinical trial (30 patients) comparing open flap debridement, L-PRF, and L-PRF plus collagen membrane; all groups improved clinically, and the collagen-membrane group had greater radiographic defect fill but no sustained difference in crevicular PDGF/VEGF levels.

Trust comment: Randomized clinical trial with defined outcomes and blinded assessor but small sample (n=30) limits precision.

Study Details

PMID:37667213
Participants:30
Impact:-56.3% (OFD), -56.6% (L-PRF), -53.0% (L-PRF+CM) at 6 months
Trust score:4/5

radiographic defect depth (CEJ-BD)

1 evidences

Randomized clinical trial (30 patients) comparing open flap debridement, L-PRF, and L-PRF plus collagen membrane; all groups improved clinically, and the collagen-membrane group had greater radiographic defect fill but no sustained difference in crevicular PDGF/VEGF levels.

Trust comment: Randomized clinical trial with defined outcomes and blinded assessor but small sample (n=30) limits precision.

Study Details

PMID:37667213
Participants:30
Impact:mean reduction +2.12 mm (L-PRF+CM), % change -32.6% (L-PRF+CM) vs -7.25% (OFD) and -12.6% (L-PRF); intergroup P=0.001
Trust score:4/5

skin water content

1 evidences

Double-blind RCT in 99 women showing daily oral collagen peptides for 12 weeks increased skin water content and natural moisturizing factor and reduced transepidermal water loss; elasticity and thickness unchanged.

Trust comment: Well-designed randomized, double-blind, placebo-controlled trial with adequate sample size and objective skin measures.

Study Details

PMID:33774639
Participants:99
Impact:increase after 12 weeks (SC and epidermis)
Trust score:5/5

transepidermal water loss (TEWL)

5 evidences

Double-blind RCT in 99 women showing daily oral collagen peptides for 12 weeks increased skin water content and natural moisturizing factor and reduced transepidermal water loss; elasticity and thickness unchanged.

Trust comment: Well-designed randomized, double-blind, placebo-controlled trial with adequate sample size and objective skin measures.

Study Details

PMID:33774639
Participants:99
Impact:decrease after 12 weeks
Trust score:5/5

Small randomized double‑blind placebo‑controlled trial of an oral fish‑derived collagen peptide plus ornithine drink given nightly for 8 weeks in adults with low skin moisture/elasticity, measuring skin elasticity, TEWL, pores, and IGF‑1.

Trust comment: Randomized double‑blind design is strong, but very small sample size and combined collagen+ornithine formulation limit generalizability and attribution to collagen alone.

Study Details

PMID:30513923
Participants:21
Impact:seasonal increase prevented in CPO group vs significant increase in placebo (between‑group difference significant)
Trust score:3/5

Daily oral collagen tripeptide (3 g) improved skin hydration and elasticity and tended to reduce transepidermal water loss over 12 weeks compared with no supplement.

Trust comment: Randomized controlled human study but small sample and multiple arms reduce power; moderate trust for reported effects on skin properties.

Study Details

PMID:24131075
Participants:32
Impact:greatest reduction observed in collagen tripeptide group (trend vs others; no exact % reported)
Trust score:3/5

Topical product containing collagen tripeptide improved objective skin barrier measures and reduced symptoms of sensitive atopic skin versus placebo over 4 weeks.

Trust comment: Randomized double-blind placebo-controlled human trial but small (n=40) and short duration (4 weeks), so moderate confidence.

Study Details

PMID:19496838
Participants:40
Impact:decreased (P<0.02)
Trust score:3/5

Randomized double-blind placebo-controlled 12-week trial of an oral plant-derived 'collagen alternative' (VC-H1) showing improvements in skin hydration, barrier function, and elasticity.

Trust comment: Well-designed randomized double-blind placebo-controlled trial with objective measures and high compliance, but limited to 12 weeks and a single ethnicity which limits generalizability.

Study Details

PMID:40806423
Participants:98
Impact:decreased from 16.9 to 16.2 AU at 12 weeks (−0.7 AU, p<0.001; greater reduction vs control)
Trust score:4/5

natural moisturizing factor (NMF) in stratum corneum

1 evidences

Double-blind RCT in 99 women showing daily oral collagen peptides for 12 weeks increased skin water content and natural moisturizing factor and reduced transepidermal water loss; elasticity and thickness unchanged.

Trust comment: Well-designed randomized, double-blind, placebo-controlled trial with adequate sample size and objective skin measures.

Study Details

PMID:33774639
Participants:99
Impact:increase after 12 weeks
Trust score:5/5

soft tissue volumetric gain (BL to 3M mean distance)

1 evidences

Randomized trial (44 patients) comparing a volume-stable collagen matrix (VCMX) to connective tissue graft (CTG) during implant placement at sites with small buccal dehiscences: both increased soft-tissue volume, CTG gave slightly more stable gains and greater keratinized tissue width while VCMX caused less short-term pain/bleeding.

Trust comment: Randomized RCT with objective 3D measures and 1-year follow-up; moderate sample size and single-center limit generalizability.

Study Details

PMID:40105088
Participants:44
Impact:VCMX 1.07 mm vs CTG 1.22 mm (no significant difference)
Trust score:4/5

keratinized tissue width (KTW)

1 evidences

Randomized trial (44 patients) comparing a volume-stable collagen matrix (VCMX) to connective tissue graft (CTG) during implant placement at sites with small buccal dehiscences: both increased soft-tissue volume, CTG gave slightly more stable gains and greater keratinized tissue width while VCMX caused less short-term pain/bleeding.

Trust comment: Randomized RCT with objective 3D measures and 1-year follow-up; moderate sample size and single-center limit generalizability.

Study Details

PMID:40105088
Participants:44
Impact:CTG > VCMX (3.9 mm vs 3.2 mm; P=0.033)
Trust score:4/5

patient-reported short-term morbidity (pain/bleeding/swelling)

1 evidences

Randomized trial (44 patients) comparing a volume-stable collagen matrix (VCMX) to connective tissue graft (CTG) during implant placement at sites with small buccal dehiscences: both increased soft-tissue volume, CTG gave slightly more stable gains and greater keratinized tissue width while VCMX caused less short-term pain/bleeding.

Trust comment: Randomized RCT with objective 3D measures and 1-year follow-up; moderate sample size and single-center limit generalizability.

Study Details

PMID:40105088
Participants:44
Impact:less with VCMX (statistically significant at early days)
Trust score:4/5

percent root coverage

2 evidences

Within-patient randomized study (30 patients) comparing volume-stable collagen matrix (VCMX) to autogenous connective tissue graft (CTG) for root coverage: CTG achieved higher percent root coverage while VCMX caused less postoperative pain and was preferred by patients.

Trust comment: Randomized, controlled, double-masked multi-site trial with within-patient pairing; modest sample but clear primary outcome differences.

Study Details

PMID:34287902
Participants:30
Impact:CTG 90.5% ±14.9% vs VCMX 70.7% ±28.3% (CTG superior)
Trust score:4/5

Both techniques with acellular dermal matrix improved root coverage; coronally positioned flap gave higher mean coverage than the tunnel technique at 4 months.

Trust comment: Randomized, masked clinical trial but small sample (n=24) and short (4-month) follow-up limits generalizability.

Study Details

PMID:18533779
Participants:24
Impact:coronally positioned flap + ADM 95% vs tunnel + ADM 78% (difference clinically notable but not statistically significant)
Trust score:3/5

soft tissue volume gain

1 evidences

Within-patient randomized study (30 patients) comparing volume-stable collagen matrix (VCMX) to autogenous connective tissue graft (CTG) for root coverage: CTG achieved higher percent root coverage while VCMX caused less postoperative pain and was preferred by patients.

Trust comment: Randomized, controlled, double-masked multi-site trial with within-patient pairing; modest sample but clear primary outcome differences.

Study Details

PMID:34287902
Participants:30
Impact:greater with CTG (P=0.0006)
Trust score:4/5

postoperative pain

4 evidences

Within-patient randomized study (30 patients) comparing volume-stable collagen matrix (VCMX) to autogenous connective tissue graft (CTG) for root coverage: CTG achieved higher percent root coverage while VCMX caused less postoperative pain and was preferred by patients.

Trust comment: Randomized, controlled, double-masked multi-site trial with within-patient pairing; modest sample but clear primary outcome differences.

Study Details

PMID:34287902
Participants:30
Impact:less with VCMX
Trust score:4/5

Randomized trial comparing PRF membrane versus collagen membrane after oral mucosal excision; PRF showed less pain and faster healing at early time points.

Trust comment: Small RCT with clear outcomes but limited sample size and short follow-up for recurrence/complications.

Study Details

PMID:29601789
Participants:30
Impact:15-day: 66.66% reported substantially less pain with PRF vs collagen; 30-day: 86.66% no pain (PRF) vs 60% (collagen)
Trust score:3/5

Randomized clinical study (60 patients) comparing PRF, PRF+collagen plug, and control after tooth extraction; evaluated ridge dimensions and postoperative pain.

Trust comment: Prospective randomized human trial (n=60) with objective measurements and CBCT; moderate–high quality though sample size modest and short follow-up (3 months).

Study Details

PMID:39064496
Participants:60
Impact:PRF and PRF+collagen groups reported lower pain at 24 h and 3 days vs control (statistically significant, p<0.05); no significant difference at 1 week
Trust score:4/5

Randomized clinical trial (63 enrolled, 58 available for follow-up) comparing apically positioned flap, free gingival graft (FGG), and a collagen matrix to increase keratinized mucosa before implant prosthesis; outcomes at 4 weeks.

Trust comment: Randomized parallel-group human trial with objective measures and reasonable follow-up; moderate quality though some dropouts and short-term endpoint.

Study Details

PMID:32159530
Participants:58
Impact:Postoperative pain significantly higher in FGG group than collagen matrix and control (collagen matrix had lower pain than FGG)
Trust score:4/5

Healing time

3 evidences

In infants with deep second-degree facial/neck burns, topical medical collagen sponge had similar or slightly faster healing but higher wound bacterial positivity compared with rhGM-CSF; combination therapy (rhGM-CSF + collagen sponge) performed best.

Trust comment: Randomized single-center pediatric RCT with clear outcomes but small group size per arm and limited blinding.

Study Details

PMID:38181297
Participants:108
Impact:−1.38 days (medical collagen sponge 18.25±3.21 d vs rhGM-CSF 19.63±2.65 d)
Trust score:3/5

Randomized trial: topical recombinant human EGF accelerated healing of diabetic foot ulcers, with greater collagen/fibroblast development in treated wounds.

Trust comment: Randomized controlled trial with clear clinical and histologic outcomes but small sample size; results appear robust for the measured endpoints.

Study Details

PMID:31878810
Participants:50
Impact:45 ± 12 days (treatment) vs 72 ± 18 days (control); difference ≈ -27 days (P < .0001)
Trust score:4/5

Randomised trial showing primary closure with collagen‑gentamicin implant reduced surgical wound infections and shortened healing time versus open wound care in contaminated abdominal wounds.

Trust comment: Randomised study with adequate sample size showing significant clinical benefits, though detailed numeric rates not reported here.

Study Details

PMID:9880419
Participants:73
Impact:decrease (shortened; P < 0.001)
Trust score:4/5

Bacterial positive rate

1 evidences

In infants with deep second-degree facial/neck burns, topical medical collagen sponge had similar or slightly faster healing but higher wound bacterial positivity compared with rhGM-CSF; combination therapy (rhGM-CSF + collagen sponge) performed best.

Trust comment: Randomized single-center pediatric RCT with clear outcomes but small group size per arm and limited blinding.

Study Details

PMID:38181297
Participants:108
Impact:+8.3 percentage points (medical collagen sponge 10/36 = 27.8% vs rhGM-CSF 7/36 = 19.4%)
Trust score:3/5

VSS total score (scar quality)

1 evidences

In infants with deep second-degree facial/neck burns, topical medical collagen sponge had similar or slightly faster healing but higher wound bacterial positivity compared with rhGM-CSF; combination therapy (rhGM-CSF + collagen sponge) performed best.

Trust comment: Randomized single-center pediatric RCT with clear outcomes but small group size per arm and limited blinding.

Study Details

PMID:38181297
Participants:108
Impact:−0.94 points (medical collagen sponge 6.22±1.92 vs rhGM-CSF 7.16±1.61)
Trust score:3/5

Radiographic union at 52 weeks

1 evidences

In open tibia fractures with bone defects, rhBMP-2 delivered on an absorbable collagen sponge showed lower radiographic union and clinical healing rates and more complications than autologous bone graft.

Trust comment: Multicenter randomized trial but small sample and missing outcome data for some patients limit confidence.

Study Details

PMID:31022069
Participants:23
Impact:−23.5 percentage points (58.3% rhBMP-2+collagen vs 81.8% autograft)
Trust score:3/5

Clinical healing at 52 weeks

1 evidences

In open tibia fractures with bone defects, rhBMP-2 delivered on an absorbable collagen sponge showed lower radiographic union and clinical healing rates and more complications than autologous bone graft.

Trust comment: Multicenter randomized trial but small sample and missing outcome data for some patients limit confidence.

Study Details

PMID:31022069
Participants:23
Impact:−27 percentage points (27% rhBMP-2+collagen vs 54% autograft)
Trust score:3/5

Major complications

3 evidences

Multicenter randomized trial showing a percutaneous collagen hemostasis device substantially reduced puncture-site hemostasis time and shortened time to ambulation versus manual compression, without increasing major complications.

Trust comment: Large multicenter randomized trial with clear, clinically relevant endpoints; some subgroup complexity but overall reliable.

Study Details

PMID:10745611
Participants:165
Impact:no increase in major complications (low incidence; NS)
Trust score:4/5

Small randomized trial comparing resorbable collagen barriers supported by plates versus titanium-reinforced nonresorbable barriers for vertical ridge augmentation; both achieved bone gain but complications occurred in both groups.

Trust comment: Blinded randomized trial but small sample (22 patients) and preliminary report limit generalizability.

Study Details

PMID:17622003
Participants:22
Impact:3 major complications leading to complete failure of augmentation (2 in resorbable barrier group, 1 in nonresorbable group)
Trust score:3/5

In open tibia fractures with bone defects, rhBMP-2 delivered on an absorbable collagen sponge showed lower radiographic union and clinical healing rates and more complications than autologous bone graft.

Trust comment: Multicenter randomized trial but small sample and missing outcome data for some patients limit confidence.

Study Details

PMID:31022069
Participants:23
Impact:+2 events (5 vs 3)
Trust score:3/5

Angiogenesis

1 evidences

Topical high‑molecular‑weight hyaluronic acid after third molar extraction reduced local inflammatory cell infiltration and increased angiogenesis at 1 week, with no change in pain or oxidative stress markers at that time point.

Trust comment: Small controlled clinical study (n=40) showing local anti-inflammatory histologic effects but limited clinical/biochemical changes at 1 week and short follow-up.

Study Details

PMID:26027861
Participants:40
Impact:increased in HA group at 1 week (statistically significant)
Trust score:3/5

12-week wound closure rate

1 evidences

In this interim analysis, standard collagen alginate dressing (control) had substantially lower 12-week ulcer closure rates than acellular fish skin graft (31.3% vs 63.0%).

Trust comment: Multicenter randomized trial with a substantial completed sample (n=94) in this interim analysis, giving moderate confidence in the comparative result.

Study Details

PMID:35797557
Participants:94
Impact:31.3% healed (15/48) with collagen alginate dressing vs 63.0% with fish skin (29/46) — collagen −31.7 percentage points
Trust score:4/5

Mean time to healing

1 evidences

In this interim analysis, standard collagen alginate dressing (control) had substantially lower 12-week ulcer closure rates than acellular fish skin graft (31.3% vs 63.0%).

Trust comment: Multicenter randomized trial with a substantial completed sample (n=94) in this interim analysis, giving moderate confidence in the comparative result.

Study Details

PMID:35797557
Participants:94
Impact:7 weeks (both groups)
Trust score:4/5

Number of applications to heal

1 evidences

In this interim analysis, standard collagen alginate dressing (control) had substantially lower 12-week ulcer closure rates than acellular fish skin graft (31.3% vs 63.0%).

Trust comment: Multicenter randomized trial with a substantial completed sample (n=94) in this interim analysis, giving moderate confidence in the comparative result.

Study Details

PMID:35797557
Participants:94
Impact:Median 6 applications for fish skin; (no value reported for collagen group)
Trust score:4/5

Keratinized mucosa (KM) gain at 12 months

1 evidences

A xenogeneic collagen matrix increased keratinized mucosa width and reduced patient pain compared with autologous grafts, but gained less KM (1.6 mm vs 2.5 mm); probing depth reductions were similar.

Trust comment: Dual-center randomized trial with reasonable sample size (n=49) and clear clinical endpoints, though surgical comparisons limit blinding.

Study Details

PMID:34651349
Participants:49
Impact:+1.6 mm (APF + collagen matrix) vs +2.5 mm (APF + free gingival graft)
Trust score:4/5

Probing pocket depth (PPD) reduction

2 evidences

Both PRF and PLA-PGA membranes combined with hydroxyapatite crystal collagen-fiber graft led to significant defect improvement at 6 months, with no significant difference between membranes.

Trust comment: Randomized parallel design but small sample (28 patients) and short follow-up (6 months) limit robustness.

Study Details

PMID:37622620
Participants:28
Impact:Significant within-group reductions; between-group difference not significant (mean difference 0.35 ± 1.90 mm)
Trust score:3/5

A xenogeneic collagen matrix increased keratinized mucosa width and reduced patient pain compared with autologous grafts, but gained less KM (1.6 mm vs 2.5 mm); probing depth reductions were similar.

Trust comment: Dual-center randomized trial with reasonable sample size (n=49) and clear clinical endpoints, though surgical comparisons limit blinding.

Study Details

PMID:34651349
Participants:49
Impact:≈1.7 mm PPD reduction with collagen matrix (similar to graft)
Trust score:4/5

Patient-reported pain/analgesic use

1 evidences

A xenogeneic collagen matrix increased keratinized mucosa width and reduced patient pain compared with autologous grafts, but gained less KM (1.6 mm vs 2.5 mm); probing depth reductions were similar.

Trust comment: Dual-center randomized trial with reasonable sample size (n=49) and clear clinical endpoints, though surgical comparisons limit blinding.

Study Details

PMID:34651349
Participants:49
Impact:Lower pain and analgesic consumption with collagen matrix (reported better tolerated)
Trust score:4/5

Estimated total blood loss

1 evidences

Topical thrombin-collagen combined with autologous PRP did not reduce perioperative blood loss or transfusion rates in primary total hip arthroplasty compared with standard care.

Trust comment: Prospective randomized single-center study with modest sample size (n=39); negative results are plausible but sample limits precision.

Study Details

PMID:30084822
Participants:39
Impact:No significant difference between thrombin-collagen+PRP and control (no numeric difference reported)
Trust score:3/5

Transfusion requirement

1 evidences

Topical thrombin-collagen combined with autologous PRP did not reduce perioperative blood loss or transfusion rates in primary total hip arthroplasty compared with standard care.

Trust comment: Prospective randomized single-center study with modest sample size (n=39); negative results are plausible but sample limits precision.

Study Details

PMID:30084822
Participants:39
Impact:No significant difference in blood transfusions received
Trust score:3/5

Postoperative hematocrit/change in hematocrit

1 evidences

Topical thrombin-collagen combined with autologous PRP did not reduce perioperative blood loss or transfusion rates in primary total hip arthroplasty compared with standard care.

Trust comment: Prospective randomized single-center study with modest sample size (n=39); negative results are plausible but sample limits precision.

Study Details

PMID:30084822
Participants:39
Impact:No significant difference in daily postoperative hematocrit or change from baseline
Trust score:3/5

knee pain (VAS)

4 evidences

12-week randomized placebo-controlled trial: small-dose undenatured type II collagen improved knee flexibility, reduced joint discomfort, and improved motor function versus placebo.

Trust comment: Randomized, double-blind, placebo-controlled RCT directly testing collagen supplement but relatively small sample (pilot-sized) so moderate-high confidence.

Study Details

PMID:35512781
Participants:58
Impact:significant reduction vs placebo
Trust score:4/5

Daily collagen hydrolysate (10 g) for 6 months reduced knee pain and improved joint comfort in people with knee osteoarthritis.

Trust comment: Large randomized double-blind multicenter trial showing symptom benefit, but paper provides limited numerical effect sizes in the abstract.

Study Details

PMID:19212858
Participants:250
Impact:Significant improvement vs control (p<0.05)
Trust score:4/5

After HA injection, adding an oral collagen-containing viscosupplement tended to improve symptoms and reduced patients' use of painkillers more than HA alone.

Trust comment: Randomized double-blind placebo-controlled trial with 100 patients, but the oral product combined multiple ingredients so effects cannot be attributed solely to collagen.

Study Details

PMID:26550817
Participants:100
Impact:positive trend toward improvement vs HA alone (not clearly reported as statistically significant)
Trust score:4/5

12 weeks of collagen peptide (10 g/day) did not reduce knee pain or change biomarkers versus placebo in active middle-aged to older adults.

Trust comment: Well-powered randomized controlled trial with clear endpoints and reported between-group comparisons, showing null effect for collagen peptides.

Study Details

PMID:31990581
Participants:167
Impact:CP: −1.6±2.4 vs Placebo: −1.9±2.6 (no between-group difference, p=0.42)
Trust score:4/5

knee function (KOOS, Lysholm)

1 evidences

12 weeks of collagen peptide (10 g/day) did not reduce knee pain or change biomarkers versus placebo in active middle-aged to older adults.

Trust comment: Well-powered randomized controlled trial with clear endpoints and reported between-group comparisons, showing null effect for collagen peptides.

Study Details

PMID:31990581
Participants:167
Impact:Both groups improved (KOOS and Lysholm increased) with no between-group difference (p>0.28)
Trust score:4/5

inflammatory/cartilage/bone biomarkers

1 evidences

12 weeks of collagen peptide (10 g/day) did not reduce knee pain or change biomarkers versus placebo in active middle-aged to older adults.

Trust comment: Well-powered randomized controlled trial with clear endpoints and reported between-group comparisons, showing null effect for collagen peptides.

Study Details

PMID:31990581
Participants:167
Impact:No change with CP versus placebo (p>0.05)
Trust score:4/5

keratinized mucosa width (KMW)

1 evidences

Xenogeneic collagen matrix (XCM) produced similar keratinized mucosa width but thinner mucosa, higher shrinkage, and better esthetics than free gingival graft at 6 months.

Trust comment: Randomized clinical trial but small sample size limits precision; outcomes and statistics reported appropriately.

Study Details

PMID:36637519
Participants:30
Impact:FGG 3.60±0.79 mm vs XCM 3.28±0.96 mm (no significant difference, p=0.186)
Trust score:3/5

keratinized mucosa thickness (KMT)

1 evidences

Xenogeneic collagen matrix (XCM) produced similar keratinized mucosa width but thinner mucosa, higher shrinkage, and better esthetics than free gingival graft at 6 months.

Trust comment: Randomized clinical trial but small sample size limits precision; outcomes and statistics reported appropriately.

Study Details

PMID:36637519
Participants:30
Impact:FGG 1.24±0.34 mm vs XCM 0.95±0.29 mm (XCM inferior, p=0.002)
Trust score:3/5

graft shrinkage rate

1 evidences

Xenogeneic collagen matrix (XCM) produced similar keratinized mucosa width but thinner mucosa, higher shrinkage, and better esthetics than free gingival graft at 6 months.

Trust comment: Randomized clinical trial but small sample size limits precision; outcomes and statistics reported appropriately.

Study Details

PMID:36637519
Participants:30
Impact:FGG 42.11% vs XCM 53.22% (higher shrinkage with XCM)
Trust score:3/5

scar assessment score (Patient & Observer Scar Assessment Scale)

1 evidences

For small head-and-neck skin defects, xenogeneic collagen matrix produced non-inferior scar outcomes at 6 months compared with skin grafts.

Trust comment: Multicenter randomized trial but small number of wounds analyzed; outcome measures and non-inferiority testing reported.

Study Details

PMID:38962824
Participants:39
Impact:XCM mean 16.55 (SD 6.8) vs skin graft 16.83 (SD 8.21); no significant difference (p=0.91)
Trust score:3/5

lumbar spine BMD

10 evidences

In men with idiopathic osteoporosis, daily intranasal salmon calcitonin increased lumbar spine BMD and suppressed bone resorption markers over 12 months.

Trust comment: 12-month double-blind randomized placebo-controlled human trial with clear BMD and marker outcomes but modest sample size.

Study Details

PMID:11874243
Participants:28
Impact:+7.1% with salmon calcitonin vs +2.4% with placebo over 12 months
Trust score:4/5

Long‑term extension of ibandronate treatment showing sustained increases in lumbar spine and hip BMD and persistent reductions in type I collagen turnover markers over 3 years.

Trust comment: Large long‑term extension with clinically meaningful BMD and biochemical outcomes; post‑hoc elements and extension design modestly limit causal strength.

Study Details

PMID:18180976
Participants:719
Impact:+7.6% (150 mg) and +6.4% (100 mg) vs baseline at 3 years (post‑hoc continuous‑treatment analysis)
Trust score:4/5

Five years of risedronate reduced bone turnover markers and increased lumbar spine BMD, with no pathologic biopsy findings.

Trust comment: Extension randomized/controlled data with paired biopsies and multiple objective bone markers; moderate sample for biopsy analyses.

Study Details

PMID:15478000
Participants:48
Impact:+9.2% vs baseline (risedronate)
Trust score:4/5

Alendronate prevented periprosthetic BMD loss around femoral implants and reduced serum N-terminal telopeptides of type-1 collagen; alfacalcidol preserved lumbar spine BMD but did not prevent periprosthetic loss.

Trust comment: Human clinical study with clear BMD and collagen turnover markers; relevant to collagen metabolism but not an intervention using collagen itself.

Study Details

PMID:21776573
Participants:60
Impact:Both alendronate and alfacalcidol > no-medication at 48 weeks (preserved BMD)
Trust score:3/5

Multicenter randomized trial of once-weekly alendronate in postmenopausal Chinese women; not designed to test Vitamin D effects.

Trust comment: Large randomized double-blind placebo-controlled multicenter trial (n=560) with objective BMD and bone turnover endpoints; high reliability.

Study Details

PMID:19343272
Participants:560
Impact:increase (significantly greater vs placebo, P < 0.001)
Trust score:4/5

Twelve weeks of maximal squat strength training increased lumbar spine and hip BMD and raised a bone formation marker and strength outcomes in young women.

Trust comment: Randomized training trial with objective BMD and biochemical measures though sample size is modest.

Study Details

PMID:24736773
Participants:30
Impact:+2.2% over 12 weeks
Trust score:4/5

Randomized trial of neridronate vs control in thalassaemia-associated osteoporosis; both groups received calcium + 400 IU vitamin D daily; neridronate increased BMD and reduced bone turnover and back pain.

Trust comment: Randomized phase 2 trial with clear clinical endpoints and 118 participants; open-label design lowers blinding robustness but results are plausible and reported with statistics.

Study Details

PMID:22571408
Participants:118
Impact:increase (significant at 6 and 12 months)
Trust score:4/5

Ibandronate and alendronate both increased BMD over 1 year; all women also received daily calcium and vitamin D 200 IU.

Trust comment: Multicenter randomized positive-control trial with 158 randomized (151 completed) and objective BMD/biomarker endpoints; good internal validity.

Study Details

PMID:19855926
Participants:151
Impact:+4.27% (mean increase)
Trust score:4/5

Alendronate prevented glucocorticoid-induced bone loss, increasing BMD at spine and hip sites over 24 weeks compared with calcium alone.

Trust comment: Randomized trial with substantial sample size and clear BMD improvements at multiple sites.

Study Details

PMID:19040000
Participants:140
Impact:+6.1% (24 weeks vs baseline)
Trust score:4/5

Oral alendronate and yearly zoledronic acid similarly increased bone density and strongly reduced bone resorption biomarkers in adults with osteogenesis imperfecta.

Trust comment: Prospective randomized 24-month study with 52 completers showing consistent BMD gains and large decreases in collagen resorption marker; well-reported outcomes.

Study Details

PMID:27482615
Participants:52
Impact:+10.5% (ALN) / +11.3% (ZOL)
Trust score:4/5

satisfaction with breasts (BREAST-Q) at 3 months

1 evidences

Short-term (3-month) patient-reported satisfaction favored Alloderm over Dermacell, but differences were not present at 12 months.

Trust comment: Randomized trial with moderate sample size and complete patient-reported outcome reporting but single-center limits generalizability.

Study Details

PMID:32893151
Participants:62
Impact:Alloderm 67 vs Dermacell 53 (p=0.03), improved at 3 months only
Trust score:3/5

overall satisfaction / surgeon / information (BREAST-Q) at 3 months

1 evidences

Short-term (3-month) patient-reported satisfaction favored Alloderm over Dermacell, but differences were not present at 12 months.

Trust comment: Randomized trial with moderate sample size and complete patient-reported outcome reporting but single-center limits generalizability.

Study Details

PMID:32893151
Participants:62
Impact:Alloderm higher for overall results (85 vs 61, p=0.003), surgeon (89 vs 67, p=0.01), information (74 vs 59, p=0.02)
Trust score:3/5

PROMs at 12 months

1 evidences

Short-term (3-month) patient-reported satisfaction favored Alloderm over Dermacell, but differences were not present at 12 months.

Trust comment: Randomized trial with moderate sample size and complete patient-reported outcome reporting but single-center limits generalizability.

Study Details

PMID:32893151
Participants:62
Impact:No significant differences between Alloderm and Dermacell at 12 months (p>0.05)
Trust score:3/5

probing depth (PD) and clinical attachment level (CAL)

1 evidences

Both treatments improved peri-implantitis clinical and radiographic outcomes, with the collagen membrane group showing better PD, CAL and vertical defect depth at 12 months.

Trust comment: Randomized clinical trial with objective clinical and radiographic endpoints but modest sample size.

Study Details

PMID:30118569
Participants:52
Impact:Both groups improved vs baseline; at 12 months PD and CAL significantly better in collagen membrane (CM) group (p<0.05)
Trust score:3/5

vertical defect depth (VDD) and defect fill (DF)

1 evidences

Both treatments improved peri-implantitis clinical and radiographic outcomes, with the collagen membrane group showing better PD, CAL and vertical defect depth at 12 months.

Trust comment: Randomized clinical trial with objective clinical and radiographic endpoints but modest sample size.

Study Details

PMID:30118569
Participants:52
Impact:VDD improved more in CM at 12 months (p<0.05); DF CM 1.99±0.76 vs CGF 1.63±1.00 (p=0.154, not significant)
Trust score:3/5

gingival index (GI) and bleeding on probing (BOP)

1 evidences

Both treatments improved peri-implantitis clinical and radiographic outcomes, with the collagen membrane group showing better PD, CAL and vertical defect depth at 12 months.

Trust comment: Randomized clinical trial with objective clinical and radiographic endpoints but modest sample size.

Study Details

PMID:30118569
Participants:52
Impact:Significant reductions in GI and BOP from baseline in both groups (p<0.05)
Trust score:3/5

daily protein intake (all PES combined)

1 evidences

Protein-enhancing strategies (including hydrolysed collagen) increased daily protein intake shortly after bariatric surgery; hydrolysed collagen had the best tolerability and satisfaction but whey produced the largest intake increase.

Trust comment: Prospective, real-world multi-arm study with reasonable sample but non-randomized allocation and self-reported dietary data limit causal inference.

Study Details

PMID:39243332
Participants:87
Impact:Increased from 54.7±21.5 to 64.7±23.4 g/day (Δ ≈ +10.0 g/day, p=0.002)
Trust score:3/5

proportion reaching ≥60 g/day

1 evidences

Protein-enhancing strategies (including hydrolysed collagen) increased daily protein intake shortly after bariatric surgery; hydrolysed collagen had the best tolerability and satisfaction but whey produced the largest intake increase.

Trust comment: Prospective, real-world multi-arm study with reasonable sample but non-randomized allocation and self-reported dietary data limit causal inference.

Study Details

PMID:39243332
Participants:87
Impact:PES users: 52% vs control 31% (odds ratio 4.2 [0.8–21.4])
Trust score:3/5

hydrolysed collagen (HC) tolerability and satisfaction

1 evidences

Protein-enhancing strategies (including hydrolysed collagen) increased daily protein intake shortly after bariatric surgery; hydrolysed collagen had the best tolerability and satisfaction but whey produced the largest intake increase.

Trust comment: Prospective, real-world multi-arm study with reasonable sample but non-randomized allocation and self-reported dietary data limit causal inference.

Study Details

PMID:39243332
Participants:87
Impact:HC: 86% used ≥5 days, 43% reached >80% advised intake, overall satisfaction ~71% (HC best tolerated among PES)
Trust score:3/5

PIIINP (type III collagen propeptide)

1 evidences

Higher blood markers of collagen turnover were linked to worse walking distance and higher risk of death or hospitalization in chronic heart failure patients.

Trust comment: Large, well-conducted observational cohort with multivariable adjustment linking collagen turnover markers to functional outcomes and prognosis.

Study Details

PMID:18672194
Participants:1009
Impact:higher PIIINP associated with decreased 6-minute walk distance and increased death/CHF hospitalization
Trust score:4/5

Width of keratinized mucosa (WKM)

1 evidences

In 30 patients, combining a free gingival graft strip with a xenogeneic collagen matrix increased keratinized mucosa; gains were significant versus baseline but between-group differences in width were not significant, while esthetics and morbidity favored the combination.

Trust comment: Randomized controlled trial with small sample (n=30) and short follow-up; outcomes clinically relevant but limited power.

Study Details

PMID:37669514
Participants:30
Impact:Significant gain vs baseline in both groups; no significant difference between groups
Trust score:3/5

Esthetic outcome (PES)

1 evidences

In 30 patients, combining a free gingival graft strip with a xenogeneic collagen matrix increased keratinized mucosa; gains were significant versus baseline but between-group differences in width were not significant, while esthetics and morbidity favored the combination.

Trust comment: Randomized controlled trial with small sample (n=30) and short follow-up; outcomes clinically relevant but limited power.

Study Details

PMID:37669514
Participants:30
Impact:Improved more in combination group (statistically significant)
Trust score:3/5

Patient morbidity (VAS pain)

1 evidences

In 30 patients, combining a free gingival graft strip with a xenogeneic collagen matrix increased keratinized mucosa; gains were significant versus baseline but between-group differences in width were not significant, while esthetics and morbidity favored the combination.

Trust comment: Randomized controlled trial with small sample (n=30) and short follow-up; outcomes clinically relevant but limited power.

Study Details

PMID:37669514
Participants:30
Impact:Lower morbidity in combination group (statistically significant)
Trust score:3/5

Radiographic bone gain

3 evidences

Secondary analysis of 33 patients (48 implants) found defect angle strongly predicted radiographic bone gain after reconstructive therapy using allograft ± collagen membrane, while other defect metrics did not.

Trust comment: Secondary analysis with modest sample size; statistically strong association for defect angle but limited by being a post hoc analysis and mixed treatments.

Study Details

PMID:37405662
Participants:33
Impact:Mean defect angle 40° → 1.85 mm bone gain; DA <57° → ≥1 mm gain; DA <30° → ≥2 mm gain
Trust score:3/5

In periodontal intraosseous defects, adding a collagen membrane to enamel matrix protein therapy did not improve clinical or radiographic outcomes compared with either therapy alone.

Trust comment: Moderate-sized clinical comparative study directly testing a collagen membrane; randomized status unclear and sample modest, but outcomes are clinical and relevant.

Study Details

PMID:12516831
Participants:61
Impact:No significant difference between combined therapy and either monotherapy at 6 months and 1 year
Trust score:3/5

Minimally invasive periodontal surgery produced clinical attachment gains at 1 year; adding deproteinized bovine bone mineral plus a collagen membrane did not improve 1-year outcomes versus surgery alone.

Trust comment: Randomized trial directly tested a collagen-containing membrane as a regenerative material; small sample size limits certainty but design is appropriate.

Study Details

PMID:34414521
Participants:31
Impact:MISTms-alone 3.00 ±1.56 mm; combined 3.85 ±1.69 mm (no significant between-group difference)
Trust score:3/5

Disease resolution

1 evidences

Secondary analysis of 33 patients (48 implants) found defect angle strongly predicted radiographic bone gain after reconstructive therapy using allograft ± collagen membrane, while other defect metrics did not.

Trust comment: Secondary analysis with modest sample size; statistically strong association for defect angle but limited by being a post hoc analysis and mixed treatments.

Study Details

PMID:37405662
Participants:33
Impact:No significant association with evaluated variables
Trust score:3/5

Recession reduction

2 evidences

In 36 split-mouth patients, both pinhole technique with collagen membrane and coronally advanced flap with connective tissue graft achieved comparable root coverage at 1 year with no significant difference in efficacy.

Trust comment: Split-mouth randomized trial with 36 patients and 1-year follow-up provides reliable comparative clinical data.

Study Details

PMID:40009192
Participants:36
Impact:Mean ~1.98 mm (CAF+CTG) vs 1.97 mm (PST+CM); no significant difference
Trust score:4/5

Adding a collagen matrix to flap surgery for gingival recession with cervical lesions gave similar coverage but increased keratinized tissue width and thickness.

Trust comment: Randomized clinical trial with 12-month follow-up and objective measures, though moderate sample size.

Study Details

PMID:34310715
Participants:62
Impact:CAF 1.9 ± 0.8 mm vs CAF+CM 2.0 ± 0.7 mm (P=0.6; no difference)
Trust score:4/5

Percentage root coverage

1 evidences

In 36 split-mouth patients, both pinhole technique with collagen membrane and coronally advanced flap with connective tissue graft achieved comparable root coverage at 1 year with no significant difference in efficacy.

Trust comment: Split-mouth randomized trial with 36 patients and 1-year follow-up provides reliable comparative clinical data.

Study Details

PMID:40009192
Participants:36
Impact:65.4% (CAF+CTG) vs 63.6% (PST+CM); no significant difference
Trust score:4/5

Width of keratinized tissue

1 evidences

In 36 split-mouth patients, both pinhole technique with collagen membrane and coronally advanced flap with connective tissue graft achieved comparable root coverage at 1 year with no significant difference in efficacy.

Trust comment: Split-mouth randomized trial with 36 patients and 1-year follow-up provides reliable comparative clinical data.

Study Details

PMID:40009192
Participants:36
Impact:CAF+CTG showed significant within-group increase (2.38 → 2.61 mm; p=0.002)
Trust score:4/5

Soft tissue thickness gain at 3 months

1 evidences

In 32 patients, a xenogeneic collagen matrix (VXCM) produced greater soft tissue thickness gain at 3 months but less gain at 6 months compared with connective tissue graft (SCTG); SCTG had better aesthetic scores and early pain was higher with SCTG.

Trust comment: Randomized, examiner-masked trial with objective 3D measurements and complete follow-up, though moderate sample size and delayed registration noted.

Study Details

PMID:40254798
Participants:32
Impact:VXCM 1.77±0.61 mm vs SCTG 1.26±0.41 mm (p=0.0003) (VXCM > SCTG)
Trust score:4/5

Soft tissue thickness gain at 6 months

1 evidences

In 32 patients, a xenogeneic collagen matrix (VXCM) produced greater soft tissue thickness gain at 3 months but less gain at 6 months compared with connective tissue graft (SCTG); SCTG had better aesthetic scores and early pain was higher with SCTG.

Trust comment: Randomized, examiner-masked trial with objective 3D measurements and complete follow-up, though moderate sample size and delayed registration noted.

Study Details

PMID:40254798
Participants:32
Impact:SCTG 1.43±0.81 mm vs VXCM 1.11±0.44 mm (p=0.0459) (SCTG > VXCM)
Trust score:4/5

Pain severity (early)

1 evidences

In 32 patients, a xenogeneic collagen matrix (VXCM) produced greater soft tissue thickness gain at 3 months but less gain at 6 months compared with connective tissue graft (SCTG); SCTG had better aesthetic scores and early pain was higher with SCTG.

Trust comment: Randomized, examiner-masked trial with objective 3D measurements and complete follow-up, though moderate sample size and delayed registration noted.

Study Details

PMID:40254798
Participants:32
Impact:Higher VAS in SCTG on day 1 (3.06 vs 1.94; p=0.002) and day 3 (1.94 vs 1.13; p=0.024)
Trust score:4/5

Body fat mass (kg)

1 evidences

In a randomized double-blind trial (initial n=90, 81 completed), daily 2000 mg skate-derived collagen peptides for 12 weeks produced small but statistically significant reductions in body fat versus placebo.

Trust comment: Well-designed double-blind RCT with DXA body composition, adequate sample size though with modest effect size and some dropouts.

Study Details

PMID:30866485
Participants:81
Impact:IG −1.2 kg vs CG +0.3 kg after 12 weeks (between-group p=0.025)
Trust score:4/5

body fat percentage

1 evidences

In a randomized double-blind trial (initial n=90, 81 completed), daily 2000 mg skate-derived collagen peptides for 12 weeks produced small but statistically significant reductions in body fat versus placebo.

Trust comment: Well-designed double-blind RCT with DXA body composition, adequate sample size though with modest effect size and some dropouts.

Study Details

PMID:30866485
Participants:81
Impact:IG −0.6% from baseline (p=0.017)
Trust score:4/5

Body weight

1 evidences

In a randomized double-blind trial (initial n=90, 81 completed), daily 2000 mg skate-derived collagen peptides for 12 weeks produced small but statistically significant reductions in body fat versus placebo.

Trust comment: Well-designed double-blind RCT with DXA body composition, adequate sample size though with modest effect size and some dropouts.

Study Details

PMID:30866485
Participants:81
Impact:CG +0.7 kg (p=0.018) while IG no significant increase
Trust score:4/5

root coverage (6 months)

1 evidences

Using a collagen matrix or enamel matrix with flap surgery improved gum root coverage and gingival thickness compared with flap alone.

Trust comment: Randomized, double-masked dual-center trial with clear clinical endpoints though group sizes were modest (n=17 per arm).

Study Details

PMID:28753100
Participants:68
Impact:CAF 68.04%; CAF+CM 87.20%; CAF+EMD 88.77%; CAF+CM+EMD 91.59%
Trust score:4/5

keratinized tissue thickness gain

1 evidences

Using a collagen matrix or enamel matrix with flap surgery improved gum root coverage and gingival thickness compared with flap alone.

Trust comment: Randomized, double-masked dual-center trial with clear clinical endpoints though group sizes were modest (n=17 per arm).

Study Details

PMID:28753100
Participants:68
Impact:Significant increase only in CM-treated groups (P<0.05)
Trust score:4/5

WOMAC pain subscale

1 evidences

Daily collagen hydrolysate (10 g) for 6 months reduced knee pain and improved joint comfort in people with knee osteoarthritis.

Trust comment: Large randomized double-blind multicenter trial showing symptom benefit, but paper provides limited numerical effect sizes in the abstract.

Study Details

PMID:19212858
Participants:250
Impact:Significant improvement vs control (p<0.05)
Trust score:4/5

NT-proANP

1 evidences

Different antihypertensive regimens produced divergent changes in circulating natriuretic peptides and some collagen turnover markers over years.

Trust comment: Biomarker sub-study of a randomized trial with modest sample size (n=93) and objective assays, but limited power for some markers.

Study Details

PMID:21446378
Participants:93
Impact:Amlodipine arm decreased by 22 pmol/L at 2 years vs atenolol arm increased by 109 pmol/L (P<0.001)
Trust score:3/5

PINP (type I procollagen aminoterminal propeptide)

1 evidences

Different antihypertensive regimens produced divergent changes in circulating natriuretic peptides and some collagen turnover markers over years.

Trust comment: Biomarker sub-study of a randomized trial with modest sample size (n=93) and objective assays, but limited power for some markers.

Study Details

PMID:21446378
Participants:93
Impact:Amlodipine: +1.8 µg/L; Atenolol: −4.7 µg/L (no differences in other collagen markers)
Trust score:3/5

intradermal collagen density

1 evidences

Polychromatic red/near‑infrared light therapy twice weekly improved skin appearance and increased intradermal collagen density versus controls.

Trust comment: Prospective randomized controlled design with objective (ultrasound, profilometry) and blinded photo assessments, though exact effect magnitudes not reported in abstract.

Study Details

PMID:24286286
Participants:136
Impact:Ultrasonographic collagen density significantly increased in treated groups vs controls
Trust score:4/5

skin roughness / fine lines / patient satisfaction

1 evidences

Polychromatic red/near‑infrared light therapy twice weekly improved skin appearance and increased intradermal collagen density versus controls.

Trust comment: Prospective randomized controlled design with objective (ultrasound, profilometry) and blinded photo assessments, though exact effect magnitudes not reported in abstract.

Study Details

PMID:24286286
Participants:136
Impact:Significant improvements in profilometry, clinical photo evaluation and patient satisfaction vs control
Trust score:4/5

ICTP (type I collagen degradation marker)

3 evidences

In women taking monophasic oral contraceptives, a transient decrease in a type I collagen synthesis marker (PICP) was observed with the lower-ethinyl-estradiol formulation after three cycles and normalized by six months; degradation marker (ICTP) was unchanged.

Trust comment: Controlled human study measuring validated collagen metabolism biomarkers in 60 women; limited by short duration and modest sample size.

Study Details

PMID:12001776
Participants:60
Impact:No significant change during the study period
Trust score:3/5

Changes in serum markers of type I collagen (ICTP and PICP) correlated with treatment response in patients with bone metastases from breast cancer.

Trust comment: Controlled clinical trial biomarker analysis with small sample (36 with serum) and clear marker–response correlations, but limited generalizability.

Study Details

PMID:8624266
Participants:36
Impact:Change in ICTP correlated with treatment response (rs = -0.57) and diagnostic accuracy 0.83 for response assessment
Trust score:3/5

In 39 older sedentary adults, 10 weeks of moderate or higher-intensity aerobic training did not change serum markers of collagen synthesis or degradation.

Trust comment: Randomized crossover design and measured biochemical outcomes support reliability, though sample size is modest.

Study Details

PMID:19815457
Participants:39
Impact:no significant change after training
Trust score:4/5

PICP (type I procollagen synthesis marker)

1 evidences

Changes in serum markers of type I collagen (ICTP and PICP) correlated with treatment response in patients with bone metastases from breast cancer.

Trust comment: Controlled clinical trial biomarker analysis with small sample (36 with serum) and clear marker–response correlations, but limited generalizability.

Study Details

PMID:8624266
Participants:36
Impact:Borderline correlation with treatment response (rs ≈ -0.37); lower diagnostic accuracy vs ICTP (0.77)
Trust score:3/5

combined defect (CD) coverage (12 months)

1 evidences

Adding a collagen matrix to flap surgery for gingival recession with cervical lesions gave similar coverage but increased keratinized tissue width and thickness.

Trust comment: Randomized clinical trial with 12-month follow-up and objective measures, though moderate sample size.

Study Details

PMID:34310715
Participants:62
Impact:CAF 55.2% vs CAF+CM 54.4% (P=0.8; no difference)
Trust score:4/5

keratinized tissue (KT) width and thickness gain

1 evidences

Adding a collagen matrix to flap surgery for gingival recession with cervical lesions gave similar coverage but increased keratinized tissue width and thickness.

Trust comment: Randomized clinical trial with 12-month follow-up and objective measures, though moderate sample size.

Study Details

PMID:34310715
Participants:62
Impact:KT width: CAF 0.3 ± 0.7 mm vs CAF+CM 0.9 ± 0.8 mm (P=0.004); KT thickness: CAF 0.1 ± 0.3 mm vs CAF+CM 0.7 ± 0.2 mm (P=0.001)
Trust score:4/5

CTX-II (type II collagen degradation)

2 evidences

In early RA, higher baseline RANKL:OPG ratio and collagen degradation markers predicted faster radiological joint damage over 11 years.

Trust comment: Prospective cohort of 155 early, untreated RA patients with long (11-year) follow-up and multivariable analyses support robustness.

Study Details

PMID:20525836
Participants:155
Impact:Higher baseline levels independently predict increased annual radiological progression
Trust score:4/5

In early rheumatoid arthritis, increases in disease activity were immediately followed by increases in urinary markers of collagen type II (cartilage) and type I (bone) degradation.

Trust comment: Well-conducted longitudinal analysis within a clinical trial cohort (n=105) using repeated biomarker and disease-activity measures.

Study Details

PMID:16126801
Participants:105
Impact:Longitudinally associated with ESR, swollen joint count and DAS28 (immediate increases with worsening arthritis)
Trust score:4/5

CTX-I (type I collagen degradation)

2 evidences

In early RA, higher baseline RANKL:OPG ratio and collagen degradation markers predicted faster radiological joint damage over 11 years.

Trust comment: Prospective cohort of 155 early, untreated RA patients with long (11-year) follow-up and multivariable analyses support robustness.

Study Details

PMID:20525836
Participants:155
Impact:Higher baseline levels independently predict increased annual radiological progression
Trust score:4/5

In early rheumatoid arthritis, increases in disease activity were immediately followed by increases in urinary markers of collagen type II (cartilage) and type I (bone) degradation.

Trust comment: Well-conducted longitudinal analysis within a clinical trial cohort (n=105) using repeated biomarker and disease-activity measures.

Study Details

PMID:16126801
Participants:105
Impact:Longitudinally associated with DAS28 (less strongly than CTX-II)
Trust score:4/5

combined operating time

1 evidences

Using a collagen matrix on the dura during hemicraniectomy reduced combined operating time and cerebrospinal fluid (CSF) complications without changing rehabilitation outcome.

Trust comment: Prospective randomized study with objective surgical endpoints but modest sample size.

Study Details

PMID:18728597
Participants:34
Impact:−19.7% (average reduction)
Trust score:4/5

cerebrospinal fluid effusion rate

1 evidences

Using a collagen matrix on the dura during hemicraniectomy reduced combined operating time and cerebrospinal fluid (CSF) complications without changing rehabilitation outcome.

Trust comment: Prospective randomized study with objective surgical endpoints but modest sample size.

Study Details

PMID:18728597
Participants:34
Impact:13% (collagen) vs 58% (control) (−45 percentage points)
Trust score:4/5

persistent CSF effusion >1 week

1 evidences

Using a collagen matrix on the dura during hemicraniectomy reduced combined operating time and cerebrospinal fluid (CSF) complications without changing rehabilitation outcome.

Trust comment: Prospective randomized study with objective surgical endpoints but modest sample size.

Study Details

PMID:18728597
Participants:34
Impact:0% (collagen) vs 33% (control)
Trust score:4/5

periorbital wrinkle area

1 evidences

Daily syrup containing fish collagen (4 g) plus CoQ10 for 12 weeks increased dermis density and reduced periorbital wrinkles and overall wrinkle score vs placebo.

Trust comment: Randomized, double-blind, placebo-controlled trial with objective measures but small sample (31 completers).

Study Details

PMID:32120787
Participants:31
Impact:−0.025 absolute (0.103 vs 0.128) corresponding to −19.4% vs placebo
Trust score:4/5

total wrinkle score (TWS)

1 evidences

Daily syrup containing fish collagen (4 g) plus CoQ10 for 12 weeks increased dermis density and reduced periorbital wrinkles and overall wrinkle score vs placebo.

Trust comment: Randomized, double-blind, placebo-controlled trial with objective measures but small sample (31 completers).

Study Details

PMID:32120787
Participants:31
Impact:−1.3 points (from 10.2 to 8.9 in test group)
Trust score:4/5

probing pocket depth (PPD)

3 evidences

In peri-implantitis surgery, both collagen matrix and autologous free gingival grafts reduced pocket depth and bleeding; autologous grafts produced greater keratinized mucosa gain at 3 years.

Trust comment: Dual-center randomized controlled trial with 3‑year follow-up, blinded assessors and intention-to-treat analysis; moderate sample size with some loss to follow-up.

Study Details

PMID:40542468
Participants:41
Impact:−1.4 mm (CM) and −1.5 mm (FGG) from baseline to 36 months
Trust score:4/5

Adding a collagen membrane plus bone mineral resulted in more radiographic bone fill but no differences in clinical signs or patient-reported outcomes at 12 months.

Trust comment: Multicenter randomized clinical trial with objective radiographic and clinical endpoints but moderate sample size.

Study Details

PMID:34169551
Participants:66
Impact:TG −1.9 mm vs CG −2.3 mm (no significant difference; p = 0.5783)
Trust score:4/5

Randomized trial in periodontitis patients showed similar pocket depth and attachment gains for both barriers but greater bone fill with the collagen membrane at 6 months.

Trust comment: Randomized clinical trial but small sample (30) and short-term follow-up; results plausible and directly measured.

Study Details

PMID:20228976
Participants:30
Impact:−2.60 mm (collagen) vs −2.50 mm (PLA) from baseline
Trust score:3/5

marginal bone loss (MBL)

2 evidences

Randomized trial comparing DBBM vs DBBM + 10% collagen for alveolar ridge preservation; overall mid-facial mucosal level and long-term tissue stability similar between materials, with some early soft tissue thickness advantage for DBBM alone.

Trust comment: Randomized clinical trial with 66 treated and 54 analyzed, one-year post-restoration follow-up and objective measures—reasonable quality though moderate sample size.

Study Details

PMID:34708422
Participants:54
Impact:no significant differences between groups over time
Trust score:4/5

At 3 years, Ti-meshes covered with collagen membranes performed similarly to Ti-reinforced d-PTFE membranes for vertical ridge augmentation around implants.

Trust comment: Randomized clinical trial with 3-year follow-up and objective measures but modest completer number (28).

Study Details

PMID:36646986
Participants:28
Impact:Mean MBL 0.70 mm overall (group A 0.73 mm; group B 0.71 mm) — no difference
Trust score:4/5

interproximal bone loss (IBL)

1 evidences

At 3 years, Ti-meshes covered with collagen membranes performed similarly to Ti-reinforced d-PTFE membranes for vertical ridge augmentation around implants.

Trust comment: Randomized clinical trial with 3-year follow-up and objective measures but modest completer number (28).

Study Details

PMID:36646986
Participants:28
Impact:Mean IBL 0.54 mm overall (group A 0.64 mm; group B 0.40 mm) — clinically similar
Trust score:4/5

keratinized tissue (tKT, wKT)

1 evidences

At 3 years, Ti-meshes covered with collagen membranes performed similarly to Ti-reinforced d-PTFE membranes for vertical ridge augmentation around implants.

Trust comment: Randomized clinical trial with 3-year follow-up and objective measures but modest completer number (28).

Study Details

PMID:36646986
Participants:28
Impact:Both groups showed increase in thickness and width of keratinized tissue (no numeric difference reported)
Trust score:4/5

type I collagen formation (PINP)

1 evidences

Cross-sectional study measuring serum collagen formation and degradation biomarkers in 617 healthy adults shows age- and sex-dependent patterns of collagen turnover (type I, III, IV).

Trust comment: Large population-based cross-sectional sample with validated biomarker assays; observational design limits causal inference.

Study Details

PMID:29596429
Participants:617
Impact:Highest at age 20–24 and declines with age (significant decrease from ~45–49 onward)
Trust score:4/5

type I collagen degradation (C1M)

1 evidences

Cross-sectional study measuring serum collagen formation and degradation biomarkers in 617 healthy adults shows age- and sex-dependent patterns of collagen turnover (type I, III, IV).

Trust comment: Large population-based cross-sectional sample with validated biomarker assays; observational design limits causal inference.

Study Details

PMID:29596429
Participants:617
Impact:Relatively stable across age groups (no major age-dependent change)
Trust score:4/5

type III collagen formation (Pro-C3)

1 evidences

Cross-sectional study measuring serum collagen formation and degradation biomarkers in 617 healthy adults shows age- and sex-dependent patterns of collagen turnover (type I, III, IV).

Trust comment: Large population-based cross-sectional sample with validated biomarker assays; observational design limits causal inference.

Study Details

PMID:29596429
Participants:617
Impact:Decreased from young to middle age then increased again in older age groups (age-dependent pattern)
Trust score:4/5

activity impairment / symptoms

1 evidences

Adding leukocyte- and platelet-rich fibrin (with or without occlusive membrane including collagen membrane stratum) to root-end surgery did not improve patient-reported pain, symptoms, activity impairment, or medication use in the first postoperative week.

Trust comment: Randomized controlled trial with 50 patients but open design and short subjective follow-up period.

Study Details

PMID:29524025
Participants:50
Impact:No significant difference between groups
Trust score:3/5

medication use

1 evidences

Adding leukocyte- and platelet-rich fibrin (with or without occlusive membrane including collagen membrane stratum) to root-end surgery did not improve patient-reported pain, symptoms, activity impairment, or medication use in the first postoperative week.

Trust comment: Randomized controlled trial with 50 patients but open design and short subjective follow-up period.

Study Details

PMID:29524025
Participants:50
Impact:No significant difference between groups
Trust score:3/5

time to hemostasis (TTH)

1 evidences

A collagen-based vascular closure device (Vascade) markedly shortened time to hemostasis, ambulation, and discharge and reduced minor access-site complications versus manual compression.

Trust comment: Large multicenter randomized trial with high follow-up completion and objective endpoints supports moderate–high trust.

Study Details

PMID:25740963
Participants:415
Impact:3.0 min vs 20.0 min (≈85% reduction vs manual compression)
Trust score:4/5

time to ambulation (TTA)

1 evidences

A collagen-based vascular closure device (Vascade) markedly shortened time to hemostasis, ambulation, and discharge and reduced minor access-site complications versus manual compression.

Trust comment: Large multicenter randomized trial with high follow-up completion and objective endpoints supports moderate–high trust.

Study Details

PMID:25740963
Participants:415
Impact:3.2 h vs 5.2 h (≈38% reduction vs manual compression)
Trust score:4/5

time to discharge eligibility (TTDe)

1 evidences

A collagen-based vascular closure device (Vascade) markedly shortened time to hemostasis, ambulation, and discharge and reduced minor access-site complications versus manual compression.

Trust comment: Large multicenter randomized trial with high follow-up completion and objective endpoints supports moderate–high trust.

Study Details

PMID:25740963
Participants:415
Impact:3.6 h vs 5.7 h (≈37% reduction vs manual compression)
Trust score:4/5

minor access-site complications

1 evidences

A collagen-based vascular closure device (Vascade) markedly shortened time to hemostasis, ambulation, and discharge and reduced minor access-site complications versus manual compression.

Trust comment: Large multicenter randomized trial with high follow-up completion and objective endpoints supports moderate–high trust.

Study Details

PMID:25740963
Participants:415
Impact:1.1% vs 7.0% (absolute −5.9 percentage points; large relative reduction)
Trust score:4/5

PINP (bone formation marker)

3 evidences

Twelve months of high-impact exercise lowered basal serum PTH but did not change bone turnover markers in premenopausal women.

Trust comment: Well-powered randomized controlled exercise trial with objective hormonal measures and clear PTH effect.

Study Details

PMID:19262975
Participants:120
Impact:No persistent change
Trust score:4/5

Twelve-week randomized study: calcium- and vitamin D–fortified milk (higher calcium + vitamin D + FOS-inulin) reduced bone resorption markers and PTH more than regular milk, especially in postmenopausal women.

Trust comment: Large randomized nutritional trial with clear endpoints and subgroup analyses; reasonable internal validity though short duration.

Study Details

PMID:26264387
Participants:257
Impact:reduced over 12 weeks in both groups
Trust score:4/5

In people with relapsing-remitting MS, weekly high-dose vitamin D raised vitamin D levels but did not meaningfully change common blood markers of bone formation or resorption over 96 weeks.

Trust comment: Randomized controlled trial in humans with 68 completers and appropriate marker measurements; limited size reduces sensitivity to small effects.

Study Details

PMID:28376767
Participants:68
Impact:No significant change (−5.10% at 48w; +10.26% at 96w; p>0.05)
Trust score:4/5

vital bone formation (%)

1 evidences

Using a bovine type I collagen membrane produced similar vital bone formation and ridge dimensions compared with a human amnion-chorion membrane in ridge preservation.

Trust comment: Randomized clinical study with histologic endpoints but small sample size limits generalizability; moderate trust.

Study Details

PMID:33031520
Participants:43
Impact:51.72% (amnion-chorion) vs 49.96% (bovine collagen membrane); no significant difference (P>0.05)
Trust score:3/5

ridge bone height/width

1 evidences

Using a bovine type I collagen membrane produced similar vital bone formation and ridge dimensions compared with a human amnion-chorion membrane in ridge preservation.

Trust comment: Randomized clinical study with histologic endpoints but small sample size limits generalizability; moderate trust.

Study Details

PMID:33031520
Participants:43
Impact:no significant differences between groups (P>0.05)
Trust score:3/5

skin hydration (corneometer)

1 evidences

Daily oral collagen tripeptide (3 g) improved skin hydration and elasticity and tended to reduce transepidermal water loss over 12 weeks compared with no supplement.

Trust comment: Randomized controlled human study but small sample and multiple arms reduce power; moderate trust for reported effects on skin properties.

Study Details

PMID:24131075
Participants:32
Impact:improved with collagen tripeptide vs no supplement (significant, p=0.011 vs control)
Trust score:3/5

skin elasticity (cutometer)

1 evidences

Daily oral collagen tripeptide (3 g) improved skin hydration and elasticity and tended to reduce transepidermal water loss over 12 weeks compared with no supplement.

Trust comment: Randomized controlled human study but small sample and multiple arms reduce power; moderate trust for reported effects on skin properties.

Study Details

PMID:24131075
Participants:32
Impact:improved with collagen tripeptide vs no supplement (significant, p=0.005 vs control)
Trust score:3/5

probing depth (PD)

6 evidences

In 45 patients with bilateral impacted lower third molars, use of bovine porous bone mineral with or without a collagen membrane reduced pocket depth and gained attachment versus untreated controls over long follow‑up.

Trust comment: Randomized assignment, long follow‑up (up to 72 months) and clinically meaningful endpoints support reasonable trust, though sample size moderate (45 patients, 90 sites).

Study Details

PMID:19254122
Participants:45
Impact:significant reduction with BPBM or BPBM + collagen membrane vs control at all time points
Trust score:4/5

Reconstructive surgery for peri-implantitis using a bovine collagen membrane or concentrated growth factor both improved clinical and radiographic outcomes; collagen membrane yielded significantly greater reductions in probing depth and vertical defect depth at 1 and 3 years.

Trust comment: Prospective randomized clinical trial with 3-year follow-up and blinded assessments; reasonable sample retention supports good trust.

Study Details

PMID:35618961
Participants:51
Impact:mean PD reduction at year 1 ≈2.21 mm (CGF) vs ≈2.60 mm (collagen membrane); greater reduction with collagen membrane (significant trend)
Trust score:4/5

Prospective randomized (non-blinded) trial comparing autogenous demineralized dentin matrix with bio-collagen membrane versus natural healing after lower third molar extraction; test group showed better probing depth and radiographic bone density but slightly greater early swelling.

Trust comment: Direct clinical use of a bio-collagen membrane was assessed in a randomized trial with adequate sample size though non-blinded allocation and limited reporting details reduce confidence.

Study Details

PMID:39786610
Participants:90
Impact:-1.94 mm (Control 4.46 ± 1.252 mm vs Test 2.52 ± 0.641 mm at 3 months)
Trust score:3/5

Residual defect height >1 mm after guided bone regeneration was associated with higher bleeding on probing and tended to increase mucosal recession at 4 years.

Trust comment: Four-year clinical follow-up is valuable, but small group sizes (n=24 total) limit precision and external validity.

Study Details

PMID:21806682
Participants:24
Impact:No meaningful difference between groups (means ~2.7–2.9 mm)
Trust score:3/5

Using a bovine bone graft plus a collagen membrane improved pocket depth and attachment in people with one intrabony periodontal defect after 1 year.

Trust comment: Randomized controlled clinical study with 1-year follow-up and clear clinical endpoints supports moderate-high trust.

Study Details

PMID:12702114
Participants:28
Impact:test (BDX+collagen): -5.3 mm (9.2 → 3.9); control (access flap): -3.8 mm (9.0 → 5.2)
Trust score:4/5

12-month RCT (51 subjects) showed guided tissue regeneration with collagen membrane improved probing depth and clinical attachment versus open flap debridement, but collagen membrane increased gingival recession compared with other treatments.

Trust comment: Randomized controlled clinical trial directly testing a collagen membrane vs alternatives with 12-month follow-up; moderate-high quality evidence.

Study Details

PMID:18834243
Participants:51
Impact:greater reduction with collagen membrane (CM) and calcium sulfate (CS) vs open flap debridement (OFD)
Trust score:4/5

radiographic vertical defect depth (VDD) / defect fill

1 evidences

Reconstructive surgery for peri-implantitis using a bovine collagen membrane or concentrated growth factor both improved clinical and radiographic outcomes; collagen membrane yielded significantly greater reductions in probing depth and vertical defect depth at 1 and 3 years.

Trust comment: Prospective randomized clinical trial with 3-year follow-up and blinded assessments; reasonable sample retention supports good trust.

Study Details

PMID:35618961
Participants:51
Impact:defect fill at year 1: 1.63±1.00 mm (CGF) vs 1.98±0.75 mm (collagen membrane); VDD reductions favored collagen membrane (p<0.001 trend)
Trust score:4/5

bleeding on probing (BOP)

3 evidences

Residual defect height >1 mm after guided bone regeneration was associated with higher bleeding on probing and tended to increase mucosal recession at 4 years.

Trust comment: Four-year clinical follow-up is valuable, but small group sizes (n=24 total) limit precision and external validity.

Study Details

PMID:21806682
Participants:24
Impact:Higher in advanced RDH (>1 mm): 54.1% vs control 29.1% (test2 vs control), significant (P = 0.02)
Trust score:3/5

In peri-implantitis surgery, both collagen matrix and autologous free gingival grafts reduced pocket depth and bleeding; autologous grafts produced greater keratinized mucosa gain at 3 years.

Trust comment: Dual-center randomized controlled trial with 3‑year follow-up, blinded assessors and intention-to-treat analysis; moderate sample size with some loss to follow-up.

Study Details

PMID:40542468
Participants:41
Impact:−40.0% (CM) and −66.6% (FGG) from baseline to 36 months
Trust score:4/5

Reconstructive surgery for peri-implantitis using a bovine collagen membrane or concentrated growth factor both improved clinical and radiographic outcomes; collagen membrane yielded significantly greater reductions in probing depth and vertical defect depth at 1 and 3 years.

Trust comment: Prospective randomized clinical trial with 3-year follow-up and blinded assessments; reasonable sample retention supports good trust.

Study Details

PMID:35618961
Participants:51
Impact:BOP decreased substantially in both groups from ≈97% baseline to ~30–40% at follow-ups (improvement in both groups)
Trust score:4/5

meniscal defect-filling ratio (meniscal volume)

1 evidences

In Asian patients with partial meniscal defects, implantation of a collagen meniscal scaffold led to measurable meniscal tissue regeneration over 12 months but clinical scores were similar to partial meniscectomy.

Trust comment: Prospective randomized multicenter trial with objective 3D MRI measures but small sample size and short (12-month) follow-up limits longer-term conclusions.

Study Details

PMID:38562624
Participants:33
Impact:+7.5% (scaffold) vs −0.4% (meniscectomy); p < 0.001
Trust score:4/5

clinical scores (VAS, IKDC, KOOS)

1 evidences

In Asian patients with partial meniscal defects, implantation of a collagen meniscal scaffold led to measurable meniscal tissue regeneration over 12 months but clinical scores were similar to partial meniscectomy.

Trust comment: Prospective randomized multicenter trial with objective 3D MRI measures but small sample size and short (12-month) follow-up limits longer-term conclusions.

Study Details

PMID:38562624
Participants:33
Impact:no significant difference between groups at 12 months
Trust score:4/5

MRI scaffold signal intensity (Genovese grade)

1 evidences

In Asian patients with partial meniscal defects, implantation of a collagen meniscal scaffold led to measurable meniscal tissue regeneration over 12 months but clinical scores were similar to partial meniscectomy.

Trust comment: Prospective randomized multicenter trial with objective 3D MRI measures but small sample size and short (12-month) follow-up limits longer-term conclusions.

Study Details

PMID:38562624
Participants:33
Impact:improved signal intensity at 12 months (p = 0.001)
Trust score:4/5

surgical site infection (SSI) incidence — overall

1 evidences

In patients undergoing vascular groin incisions, gentamicin-containing collagen implants did not significantly reduce overall surgical site infection (SSI) rates, but post-hoc analysis showed a large reduction in SSIs at high-risk centers.

Trust comment: Large multicenter randomized trial but underpowered relative to planned sample size and some findings (site-specific) are post hoc.

Study Details

PMID:32094049
Participants:288
Impact:7% (implants) vs 12% (control); p = 0.17 (not significant)
Trust score:4/5

surgical site infection (SSI) incidence — high-risk centers (post hoc)

1 evidences

In patients undergoing vascular groin incisions, gentamicin-containing collagen implants did not significantly reduce overall surgical site infection (SSI) rates, but post-hoc analysis showed a large reduction in SSIs at high-risk centers.

Trust comment: Large multicenter randomized trial but underpowered relative to planned sample size and some findings (site-specific) are post hoc.

Study Details

PMID:32094049
Participants:288
Impact:1% (implants) vs 22% (control); p < 0.001
Trust score:4/5

secondary outcomes (time to infection, length of stay, reoperation)

1 evidences

In patients undergoing vascular groin incisions, gentamicin-containing collagen implants did not significantly reduce overall surgical site infection (SSI) rates, but post-hoc analysis showed a large reduction in SSIs at high-risk centers.

Trust comment: Large multicenter randomized trial but underpowered relative to planned sample size and some findings (site-specific) are post hoc.

Study Details

PMID:32094049
Participants:288
Impact:no significant differences between groups
Trust score:4/5

infarct scar size (CMR)

1 evidences

Injectable bovine collagen hydrogel carrying mesenchymal stromal cells given at CABG was safe and associated with reduced infarct scar size at 12 months and improved LVEF in patients with low baseline LVEF.

Trust comment: Randomized single-center phase 1 trial showing promising efficacy signals but small sample size and single-center design limit generalizability.

Study Details

PMID:32910197
Participants:50
Impact:mean change −3.10% at 12 months in collagen+cells group (95% CI −6.20 to −0.02); P = 0.05
Trust score:3/5

left ventricular ejection fraction (LVEF) in low-LVEF subgroup (≤40%)

1 evidences

Injectable bovine collagen hydrogel carrying mesenchymal stromal cells given at CABG was safe and associated with reduced infarct scar size at 12 months and improved LVEF in patients with low baseline LVEF.

Trust comment: Randomized single-center phase 1 trial showing promising efficacy signals but small sample size and single-center design limit generalizability.

Study Details

PMID:32910197
Participants:50
Impact:increase ~+9.35% at 12 months in collagen+cells subgroup (significant)
Trust score:3/5

safety (serious adverse events)

1 evidences

Injectable bovine collagen hydrogel carrying mesenchymal stromal cells given at CABG was safe and associated with reduced infarct scar size at 12 months and improved LVEF in patients with low baseline LVEF.

Trust comment: Randomized single-center phase 1 trial showing promising efficacy signals but small sample size and single-center design limit generalizability.

Study Details

PMID:32910197
Participants:50
Impact:no increase in serious adverse events vs control within 12 months
Trust score:3/5

newly formed bone area (B.Ar)

1 evidences

Adding a resorbable collagen membrane over customized titanium mesh did not significantly change histological measures of augmented bone after 6 months compared with mesh alone.

Trust comment: Randomized clinical trial with direct histomorphometric endpoints but small sample size limits power to detect modest effects.

Study Details

PMID:37966057
Participants:30
Impact:34.3% (mesh alone) vs 35.3% (mesh + collagen membrane); no significant difference
Trust score:3/5

grafting material and non-mineralized tissue areas (G.Ar, NMT.Ar)

1 evidences

Adding a resorbable collagen membrane over customized titanium mesh did not significantly change histological measures of augmented bone after 6 months compared with mesh alone.

Trust comment: Randomized clinical trial with direct histomorphometric endpoints but small sample size limits power to detect modest effects.

Study Details

PMID:37966057
Participants:30
Impact:similar between groups (no significant difference)
Trust score:3/5

time to 95% wound healing

1 evidences

In patients with major burns, daily collagen hydrolysate (40 g) with or without omega-3 accelerated wound healing, reduced days to near-complete and complete healing, and improved scar scores versus placebo over four weeks.

Trust comment: Randomized clinical trial with clear wound healing endpoints and statistically significant effects, but relatively small sample and short follow-up warrant confirmation in larger trials.

Study Details

PMID:36724726
Participants:66
Impact:Collagen: 21.3 ± 6.8 days; Collagen+ω-3: 22.9 ± 8.7 days vs Placebo: 34.3 ± 14.8 days (p = 0.003 and p = 0.03)
Trust score:4/5

time to complete wound healing

2 evidences

In patients with major burns, daily collagen hydrolysate (40 g) with or without omega-3 accelerated wound healing, reduced days to near-complete and complete healing, and improved scar scores versus placebo over four weeks.

Trust comment: Randomized clinical trial with clear wound healing endpoints and statistically significant effects, but relatively small sample and short follow-up warrant confirmation in larger trials.

Study Details

PMID:36724726
Participants:66
Impact:Collagen: 26 ± 7.7 days; Collagen+ω-3: 27.4 ± 9.4 days vs Placebo: 41.1 ± 16.6 days (p = 0.003 and p = 0.01)
Trust score:4/5

A porcine collagen-elastin dermal substitute plus STSG slowed early graft take and epithelialization versus STSG alone but showed improved scar elasticity at 12 months.

Trust comment: Phase I/II intrapatient randomized trial with objective measures and long-term follow-up but modest sample size and early wound-healing delays.

Study Details

PMID:37729164
Participants:24
Impact:+12 days (28 vs 16 days; p=0.004)
Trust score:3/5

scar quality (Vancouver Scar Scale)

1 evidences

In patients with major burns, daily collagen hydrolysate (40 g) with or without omega-3 accelerated wound healing, reduced days to near-complete and complete healing, and improved scar scores versus placebo over four weeks.

Trust comment: Randomized clinical trial with clear wound healing endpoints and statistically significant effects, but relatively small sample and short follow-up warrant confirmation in larger trials.

Study Details

PMID:36724726
Participants:66
Impact:VSS significantly lower (better) in both intervention groups vs placebo (p = 0.02 and p = 0.01)
Trust score:4/5

postoperative pain (VAS)

3 evidences

Adding cyanoacrylate over a hemostatic collagen sponge on palatal donor sites reduced postoperative pain and analgesic use after graft harvesting.

Trust comment: Randomized clinical trial (n=44) showing significant patient-reported outcomes; moderate sample size limits precision but design is appropriate.

Study Details

PMID:29713890
Participants:44
Impact:significantly decreased with cyanoacrylate over collagen sponge
Trust score:3/5

Using different wound dressings (including a collagen plug control) after palatal graft harvest changed pain and painkiller use; stents and biologic dressings reduced pain and analgesic use.

Trust comment: Good-quality randomized controlled trial with adequate sample (n=72), 100% retention, and appropriate analyses.

Study Details

PMID:35754198
Participants:72
Impact:Mean daily pain: CPS 4.2 → CPC 2.2 (-2.0), PRF 1.9 (-2.3), PS 1.0 (-3.2); test groups significantly lower vs CPS (P<0.0001, differences most pronounced first 10 days)
Trust score:5/5

In 40 patients undergoing sinus augmentation, covering the lateral window with a collagen membrane produced comparable bone formation, surgical outcomes, and patient discomfort to bony wall repositioning.

Trust comment: Prospective randomized clinical and histological study with complete clinical follow-up but loss of 11/40 biopsies for histology.

Study Details

PMID:35593928
Participants:40
Impact:numerically lower in bony wall group across first 3 days but not statistically significant
Trust score:4/5

Bleeding on probing (BoP % of sites)

1 evidences

Daily intake of a specific collagen peptide supplement plus standard periodontal maintenance reduced gum inflammation more than placebo over 3 months.

Trust comment: Double-blind RCT with appropriate outcomes and statistics but small sample and short (3-month) follow-up limit generalizability.

Study Details

PMID:36364735
Participants:39
Impact:−7.4 percentage points (10.4% → 3.0%) in test group; between-group p<0.017
Trust score:4/5

Periodontal Inflamed Surface Area (PISA, mm²)

1 evidences

Daily intake of a specific collagen peptide supplement plus standard periodontal maintenance reduced gum inflammation more than placebo over 3 months.

Trust comment: Double-blind RCT with appropriate outcomes and statistics but small sample and short (3-month) follow-up limit generalizability.

Study Details

PMID:36364735
Participants:39
Impact:−116.9 mm² (170.6 → 53.7) in test group; between-group p≤0.011
Trust score:4/5

Gingival index (GI)

1 evidences

Daily intake of a specific collagen peptide supplement plus standard periodontal maintenance reduced gum inflammation more than placebo over 3 months.

Trust comment: Double-blind RCT with appropriate outcomes and statistics but small sample and short (3-month) follow-up limit generalizability.

Study Details

PMID:36364735
Participants:39
Impact:−0.4 points (0.5 → 0.1) in test group; between-group p≤0.029
Trust score:4/5

Composite treatment success (no BoP/SoP, PPD ≤5 mm, buccal REC ≤1 mm)

1 evidences

Placing a resorbable collagen membrane over a bone graft in peri-implant reconstructive surgery did not improve clinical or radiographic outcomes at 12 months and was associated with more short-term complications and pain.

Trust comment: Randomized clinical trial directly assessing a collagen device with clear endpoints, but modest sample size and some increased device-related complications.

Study Details

PMID:36802084
Participants:43
Impact:36.8% (test with membrane) vs 45.0% (control) at 12 months; no significant difference (p=0.61)
Trust score:3/5

Probing pocket depth (PPD) and BoP/SoP

1 evidences

Placing a resorbable collagen membrane over a bone graft in peri-implant reconstructive surgery did not improve clinical or radiographic outcomes at 12 months and was associated with more short-term complications and pain.

Trust comment: Randomized clinical trial directly assessing a collagen device with clear endpoints, but modest sample size and some increased device-related complications.

Study Details

PMID:36802084
Participants:43
Impact:No significant between-group differences in changes at 6 or 12 months
Trust score:3/5

Post-surgical complications / short-term morbidity

1 evidences

Placing a resorbable collagen membrane over a bone graft in peri-implant reconstructive surgery did not improve clinical or radiographic outcomes at 12 months and was associated with more short-term complications and pain.

Trust comment: Randomized clinical trial directly assessing a collagen device with clear endpoints, but modest sample size and some increased device-related complications.

Study Details

PMID:36802084
Participants:43
Impact:+ complications observed only in membrane (test) group; ~+10 min operative time (p<0.05) and higher self-reported pain at 2 weeks (p<0.01)
Trust score:3/5

PUSH score (pressure ulcer healing)

1 evidences

Oral collagen hydrolysate high in bioactive dipeptides (CH-b) significantly improved pressure ulcer healing (PUSH, PSST, wound area) versus placebo over 16 weeks; a lower-dipeptide product (CH-a) showed smaller benefits.

Trust comment: Multi-center, double-blind randomized trial with adequate sample and clinically relevant endpoints, though some biochemical changes and sponsor involvement warrant cautious interpretation.

Study Details

PMID:30061579
Participants:112
Impact:Week 16: CH-b 6.46 vs placebo 9.26 (difference −2.8 points; p<0.01); CH-a 8.21 vs placebo 9.26 (−1.05; p=0.029)
Trust score:4/5

PSST score

1 evidences

Oral collagen hydrolysate high in bioactive dipeptides (CH-b) significantly improved pressure ulcer healing (PUSH, PSST, wound area) versus placebo over 16 weeks; a lower-dipeptide product (CH-a) showed smaller benefits.

Trust comment: Multi-center, double-blind randomized trial with adequate sample and clinically relevant endpoints, though some biochemical changes and sponsor involvement warrant cautious interpretation.

Study Details

PMID:30061579
Participants:112
Impact:Week 16: CH-b 19.71 vs placebo 23.38 (difference −3.67 points; p=0.01)
Trust score:4/5

Wound area (cm²)

1 evidences

Oral collagen hydrolysate high in bioactive dipeptides (CH-b) significantly improved pressure ulcer healing (PUSH, PSST, wound area) versus placebo over 16 weeks; a lower-dipeptide product (CH-a) showed smaller benefits.

Trust comment: Multi-center, double-blind randomized trial with adequate sample and clinically relevant endpoints, though some biochemical changes and sponsor involvement warrant cautious interpretation.

Study Details

PMID:30061579
Participants:112
Impact:Week 16: CH-b 3.19 vs placebo 5.00 (difference −1.81 cm²; p=0.027)
Trust score:4/5

Clinical response (Paulus composite criteria)

1 evidences

Oral type II collagen (various low doses) was tested in active rheumatoid arthritis; the lowest dose (20 µg/day) showed a statistically significant increase in response by one composite criterion (Paulus) but overall effects were modest.

Trust comment: Large multicenter double-blind RCT with reasonable completion rate but modest and inconsistent efficacy signals.

Study Details

PMID:9485087
Participants:227
Impact:20 µg/day group showed a statistically significant higher cumulative response vs placebo (p=0.035)
Trust score:3/5

Other composite response measures (ACR, joint counts)

1 evidences

Oral type II collagen (various low doses) was tested in active rheumatoid arthritis; the lowest dose (20 µg/day) showed a statistically significant increase in response by one composite criterion (Paulus) but overall effects were modest.

Trust comment: Large multicenter double-blind RCT with reasonable completion rate but modest and inconsistent efficacy signals.

Study Details

PMID:9485087
Participants:227
Impact:Numeric trends favored 20 µg group but were not consistently statistically significant
Trust score:3/5

safety/adverse events

3 evidences

Randomized trial in diabetic foot ulcers compared oxidized regenerated cellulose/collagen dressing, autologous growth factors, and their combination over 8 weeks.

Trust comment: Prospective randomized clinical trial with clear endpoints and statistically significant results though modest sample size.

Study Details

PMID:17967712
Participants:51
Impact:no major adverse events reported
Trust score:4/5

Oral type II collagen (various low doses) was tested in active rheumatoid arthritis; the lowest dose (20 µg/day) showed a statistically significant increase in response by one composite criterion (Paulus) but overall effects were modest.

Trust comment: Large multicenter double-blind RCT with reasonable completion rate but modest and inconsistent efficacy signals.

Study Details

PMID:9485087
Participants:227
Impact:No treatment-related adverse events detected
Trust score:3/5

In 372 adults, autologous fibroblast injections significantly improved nasolabial fold wrinkles versus placebo with mostly mild adverse events.

Trust comment: Large multicenter double-blind placebo-controlled RCT with validated scales and robust sample size (n=372).

Study Details

PMID:22409385
Participants:372
Impact:adverse events generally mild and treatment well tolerated
Trust score:5/5

MMP-9

1 evidences

In patients with ischaemic cardiomyopathy, CRT improved measures of collagen metabolism and cardiac function compared with medical therapy alone.

Trust comment: Human study with relevant biomarker and echo measures but small groups (12 vs 15) limit generalizability.

Study Details

PMID:23569146
Participants:47
Impact:elevated in ICM vs controls; lower in CRT group vs non-CRT after 12 weeks
Trust score:3/5

TIMP-1

1 evidences

In patients with ischaemic cardiomyopathy, CRT improved measures of collagen metabolism and cardiac function compared with medical therapy alone.

Trust comment: Human study with relevant biomarker and echo measures but small groups (12 vs 15) limit generalizability.

Study Details

PMID:23569146
Participants:47
Impact:elevated in ICM vs controls; lower in CRT group vs non-CRT after 12 weeks
Trust score:3/5

PICP/ICTP ratio

1 evidences

In patients with ischaemic cardiomyopathy, CRT improved measures of collagen metabolism and cardiac function compared with medical therapy alone.

Trust comment: Human study with relevant biomarker and echo measures but small groups (12 vs 15) limit generalizability.

Study Details

PMID:23569146
Participants:47
Impact:reduced in ICM vs controls; increased with CRT vs non-CRT after 12 weeks
Trust score:3/5

Total hip BMD (DXA)

1 evidences

In postmenopausal women, alendronate produced larger short-term changes in bone turnover markers (including collagen propeptide) than DXA over 6 months.

Trust comment: Randomized study with repeated biochemical measures in humans, but small sample (n=26) limits precision.

Study Details

PMID:10234582
Participants:26
Impact:mean difference +4.3% (vs control) at 6 months
Trust score:4/5

NTX (resorption marker)

1 evidences

In postmenopausal women, alendronate produced larger short-term changes in bone turnover markers (including collagen propeptide) than DXA over 6 months.

Trust comment: Randomized study with repeated biochemical measures in humans, but small sample (n=26) limits precision.

Study Details

PMID:10234582
Participants:26
Impact:~ -49% change with alendronate vs control
Trust score:4/5

CICP (collagen type I C-terminal propeptide)

1 evidences

In postmenopausal women, alendronate produced larger short-term changes in bone turnover markers (including collagen propeptide) than DXA over 6 months.

Trust comment: Randomized study with repeated biochemical measures in humans, but small sample (n=26) limits precision.

Study Details

PMID:10234582
Participants:26
Impact:~ -31% change with alendronate vs control
Trust score:4/5

PICP (procollagen type I C-terminal propeptide)

1 evidences

In children with ALL, intensive chemotherapy and glucocorticoids suppressed bone and collagen turnover markers, with rebound increases after steroid cessation modified by methotrexate.

Trust comment: Prospective longitudinal human study with frequent measures but small pediatric sample and disease-specific context limit generalizability.

Study Details

PMID:9745414
Participants:22
Impact:decreased during induction/intensification; increased markedly after prednisolone cessation
Trust score:3/5

ICTP (C-terminal telopeptide of type I collagen)

1 evidences

In children with ALL, intensive chemotherapy and glucocorticoids suppressed bone and collagen turnover markers, with rebound increases after steroid cessation modified by methotrexate.

Trust comment: Prospective longitudinal human study with frequent measures but small pediatric sample and disease-specific context limit generalizability.

Study Details

PMID:9745414
Participants:22
Impact:decreased during induction; increased after prednisolone cessation (greater with high-dose methotrexate)
Trust score:3/5

P3NP (procollagen type III N-terminal propeptide)

1 evidences

In children with ALL, intensive chemotherapy and glucocorticoids suppressed bone and collagen turnover markers, with rebound increases after steroid cessation modified by methotrexate.

Trust comment: Prospective longitudinal human study with frequent measures but small pediatric sample and disease-specific context limit generalizability.

Study Details

PMID:9745414
Participants:22
Impact:decreased during induction; increased post-glucocorticoid (greater with methotrexate)
Trust score:3/5

Skin collagen level

1 evidences

In 30 women, combined acupotomy subcision plus hyaluronic acid produced greater increases in skin collagen and elasticity and greater wrinkle improvement than either treatment alone.

Trust comment: Randomized trial in humans with objective measures but small arms (10 per group) and short follow-up.

Study Details

PMID:40296541
Participants:30
Impact:increased at 1 and 6 months post-treatment; greatest increase in AS+HA group
Trust score:3/5

ATNLS (neck wrinkle severity)

1 evidences

In 30 women, combined acupotomy subcision plus hyaluronic acid produced greater increases in skin collagen and elasticity and greater wrinkle improvement than either treatment alone.

Trust comment: Randomized trial in humans with objective measures but small arms (10 per group) and short follow-up.

Study Details

PMID:40296541
Participants:30
Impact:scores reduced at 1 and 6 months; AS+HA group showed significant decrease at 6 months
Trust score:3/5

Bone defect volume reduction

1 evidences

Adding bone marrow aspirate in a hydroxyapatite–collagen sponge led to faster bone regeneration and less postoperative morbidity in maxillofacial cystic defects compared with hydroxyapatite alone.

Trust comment: Prospective randomized study in humans (n=30) showing beneficial short-term effects but limited by small size and short follow-up.

Study Details

PMID:30845084
Participants:30
Impact:significantly greater at 3 and 6 months with bone marrow aspirate + hydroxyapatite–collagen sponge
Trust score:3/5

Postoperative pain and swelling

1 evidences

Adding bone marrow aspirate in a hydroxyapatite–collagen sponge led to faster bone regeneration and less postoperative morbidity in maxillofacial cystic defects compared with hydroxyapatite alone.

Trust comment: Prospective randomized study in humans (n=30) showing beneficial short-term effects but limited by small size and short follow-up.

Study Details

PMID:30845084
Participants:30
Impact:reduced in group receiving bone marrow aspirate with collagen sponge
Trust score:3/5

Tooth mobility

1 evidences

Adding bone marrow aspirate in a hydroxyapatite–collagen sponge led to faster bone regeneration and less postoperative morbidity in maxillofacial cystic defects compared with hydroxyapatite alone.

Trust comment: Prospective randomized study in humans (n=30) showing beneficial short-term effects but limited by small size and short follow-up.

Study Details

PMID:30845084
Participants:30
Impact:no tooth mobility at 3 months in bone marrow aspirate + collagen group
Trust score:3/5

Bone resorption markers (DPD, NTX, CTX)

1 evidences

In men with idiopathic osteoporosis, daily intranasal salmon calcitonin increased lumbar spine BMD and suppressed bone resorption markers over 12 months.

Trust comment: 12-month double-blind randomized placebo-controlled human trial with clear BMD and marker outcomes but modest sample size.

Study Details

PMID:11874243
Participants:28
Impact:significantly suppressed with calcitonin
Trust score:4/5

PICP (procollagen type I extension peptides)

1 evidences

In men with idiopathic osteoporosis, daily intranasal salmon calcitonin increased lumbar spine BMD and suppressed bone resorption markers over 12 months.

Trust comment: 12-month double-blind randomized placebo-controlled human trial with clear BMD and marker outcomes but modest sample size.

Study Details

PMID:11874243
Participants:28
Impact:reduced to a lesser extent with calcitonin
Trust score:4/5

PINP (type I collagen synthesis marker)

1 evidences

In 39 older sedentary adults, 10 weeks of moderate or higher-intensity aerobic training did not change serum markers of collagen synthesis or degradation.

Trust comment: Randomized crossover design and measured biochemical outcomes support reliability, though sample size is modest.

Study Details

PMID:19815457
Participants:39
Impact:no significant change after training
Trust score:4/5

PIIINP (type III collagen synthesis marker)

1 evidences

In 39 older sedentary adults, 10 weeks of moderate or higher-intensity aerobic training did not change serum markers of collagen synthesis or degradation.

Trust comment: Randomized crossover design and measured biochemical outcomes support reliability, though sample size is modest.

Study Details

PMID:19815457
Participants:39
Impact:no significant change after training
Trust score:4/5

PRO-C3 diagnostic performance

1 evidences

In 72 biliary tract cancer patients, multiple serum collagen-fragment biomarkers were elevated versus controls; PRO-C3 showed excellent diagnostic performance and PRO-C8 strongly predicted worse survival.

Trust comment: Moderate-sized, multicenter cohort with validated assays and multivariate adjustments, though retrospective/explanatory analyses and limited external validation reduce certainty.

Study Details

PMID:39905306
Participants:72
Impact:AUROC 0.98 (sensitivity 0.92, specificity 0.94) to discriminate BTC vs controls
Trust score:4/5

PRO-C8 (prognostic biomarker)

1 evidences

In 72 biliary tract cancer patients, multiple serum collagen-fragment biomarkers were elevated versus controls; PRO-C3 showed excellent diagnostic performance and PRO-C8 strongly predicted worse survival.

Trust comment: Moderate-sized, multicenter cohort with validated assays and multivariate adjustments, though retrospective/explanatory analyses and limited external validation reduce certainty.

Study Details

PMID:39905306
Participants:72
Impact:High PRO-C8: median OS 198 days vs low PRO-C8: 470 days (log-rank p=0.0002); predicted PFS as well
Trust score:4/5

collagen turnover marker levels

1 evidences

In 72 biliary tract cancer patients, multiple serum collagen-fragment biomarkers were elevated versus controls; PRO-C3 showed excellent diagnostic performance and PRO-C8 strongly predicted worse survival.

Trust comment: Moderate-sized, multicenter cohort with validated assays and multivariate adjustments, though retrospective/explanatory analyses and limited external validation reduce certainty.

Study Details

PMID:39905306
Participants:72
Impact:Seven markers (PRO-C3, PRO-C8, PRO-C11, PRO-C17, reC1M, C3M, TUM) significantly elevated in patients vs controls (p<0.0001)
Trust score:4/5

lean body mass

1 evidences

Double-blind RCT: a multi-ingredient supplement (included 300 mg calcium citrate) plus resistance training increased lean body mass and some upper-body muscle size measures more than an isonitrogenous placebo.

Trust comment: Double-blind randomized trial with objective outcomes but small sample size limits precision.

Study Details

PMID:33756525
Participants:26
Impact:SUPP +4.1±1.3 kg vs PL +2.8±1.7 kg (SUPP greater, P<0.05)
Trust score:3/5

healing rate (no recurrence at 1 year)

1 evidences

In 83 patients undergoing endoanal advancement flap repair, adding local gentamicin-collagen did not significantly improve 1-year healing rates compared to surgery alone.

Trust comment: Randomized clinical trial with reasonable sample size and clear clinical endpoint; negative result reduces concern for bias.

Study Details

PMID:16952209
Participants:83
Impact:overall 57% (47/83); gentamicin-collagen 26/42 vs control 21/41 (no significant difference)
Trust score:4/5

VICM (citrullinated vimentin) diagnostic power

1 evidences

In cohorts totalling 225 subjects (discovery and validation), specific collagen- and vimentin-derived serum fragments differentiated Crohn's disease from ulcerative colitis and non-IBD controls with good diagnostic accuracy.

Trust comment: Well-powered discovery and independent validation cohorts with appropriate statistical analysis and assay methods support robustness.

Study Details

PMID:26188349
Participants:225
Impact:AUC 0.77 for CD vs UC (discovery); combined panels reached AUCs up to 0.90–0.98
Trust score:4/5

C3M (MMP-degraded type III collagen)

1 evidences

In cohorts totalling 225 subjects (discovery and validation), specific collagen- and vimentin-derived serum fragments differentiated Crohn's disease from ulcerative colitis and non-IBD controls with good diagnostic accuracy.

Trust comment: Well-powered discovery and independent validation cohorts with appropriate statistical analysis and assay methods support robustness.

Study Details

PMID:26188349
Participants:225
Impact:AUC 0.69 (CD vs UC) and strong contributor to multi-marker panels (panel AUCs 0.90–0.98)
Trust score:4/5

combined biomarker panels

1 evidences

In cohorts totalling 225 subjects (discovery and validation), specific collagen- and vimentin-derived serum fragments differentiated Crohn's disease from ulcerative colitis and non-IBD controls with good diagnostic accuracy.

Trust comment: Well-powered discovery and independent validation cohorts with appropriate statistical analysis and assay methods support robustness.

Study Details

PMID:26188349
Participants:225
Impact:VICM+C3M+C4M AUC=0.90 (CD vs UC); VICM+C3M AUC=0.98 (UC vs non-IBD)
Trust score:4/5

infection rate

3 evidences

Adding rhBMP-2 delivered on an absorbable collagen sponge did not significantly accelerate fracture healing and showed a non‑significant trend toward higher infection.

Trust comment: Large randomized human trial using an absorbable collagen sponge as a delivery matrix; relevant to collagen-containing medical devices though the active agent was rhBMP-2.

Study Details

PMID:21454742
Participants:277
Impact:19% vs 11% in rhBMP-2/ACS vs SOC (p=0.0645, non‑significant trend toward increase)
Trust score:3/5

Placing a gentamicin-containing collagen sponge into the wound after pilonidal sinus surgery sped healing and reduced infections and recurrences compared with oral antibiotics alone.

Trust comment: Prospective randomized study with clearly reported clinical outcomes and adequate sample size (80), though numeric effect sizes not provided for each outcome in the text.

Study Details

PMID:20819439
Participants:80
Impact:decreased infection rate (significant)
Trust score:4/5

Multicentre RCT comparing dPTFE vs collagen membrane for lateral bone augmentation at anterior maxilla; similar alveolar width outcomes but higher infection with dPTFE.

Trust comment: Randomized multicentre trial with complete 1-year follow-up; small sample size but appropriate design and clear infection signal.

Study Details

PMID:40298001
Participants:36
Impact:dPTFE 33% (6/18) vs collagen membrane 0% (0/18), p=0.019
Trust score:4/5

skin thickness

1 evidences

In 50 patients randomized to ACHA versus Restylane, the amino-acid cross-linked HA filler promoted dermal fibroblast activity, increased skin thickness and collagen generation and provided longer-lasting volume.

Trust comment: Randomized clinical component (n=50) with supportive in vitro and animal data; moderate sample size and industry translation but not a nutritional collagen intervention.

Study Details

PMID:37265096
Participants:50
Impact:increased epithelial/dermal thickness in models and clinically
Trust score:3/5

Disease Activity Score

1 evidences

Daily low-dose bovine type II collagen (0.5 mg) modestly improved rheumatoid arthritis activity over 6 months.

Trust comment: Randomized double-blind controlled human trial with clear statistically significant improvements for the 0.5 mg dose but small sample size.

Study Details

PMID:11592359
Participants:55
Impact:-19% (0.5 mg group) vs -3% (placebo) at 24 weeks
Trust score:4/5

ACR20 response

3 evidences

Oral chicken type II collagen (0.25 mg/day) showed no statistically significant benefit over placebo in active rheumatoid arthritis over 6 months.

Trust comment: Double-blind RCT but small sample (60) and no significant primary outcome; moderate-risk of type II error.

Study Details

PMID:11072596
Participants:60
Impact:higher in collagen group but not statistically significant (no exact significant difference)
Trust score:3/5

Adding low‑dose oral bovine type II collagen to existing rheumatoid arthritis therapy did not improve outcomes versus placebo over 6 months.

Trust comment: Large (n=190) double‑blind, placebo‑controlled randomized trial showing no clinical benefit of oral type II collagen.

Study Details

PMID:10366113
Participants:190
Impact:no significant difference (placebo 20.0% vs collagen 16.84% at 6 months)
Trust score:4/5

Daily low-dose bovine type II collagen (0.5 mg) modestly improved rheumatoid arthritis activity over 6 months.

Trust comment: Randomized double-blind controlled human trial with clear statistically significant improvements for the 0.5 mg dose but small sample size.

Study Details

PMID:11592359
Participants:55
Impact:11 responders in 0.5 mg group vs 3 responders in each other group (total 20 responders)
Trust score:4/5

Horizontal dimensional change

1 evidences

RCT comparing immediate implants with or without DBBM-C (10% collagen); adding DBBM-C slightly reduced tissue dimensional changes with one significant benefit at the distal papilla.

Trust comment: Prospective randomized controlled clinical trial with complete 12-month follow-up but modest sample size (n=32).

Study Details

PMID:31815977
Participants:32
Impact:slightly less change with DBBM-C but not statistically significant
Trust score:4/5

Procollagen type III (marker of collagen turnover)

1 evidences

Exogenous growth hormone increased blood markers of bone and collagen turnover in healthy adults in a dose-dependent manner.

Trust comment: Multicenter, randomized, double-blind, placebo-controlled trial with 99 healthy volunteers and clear biomarker changes.

Study Details

PMID:10770189
Participants:99
Impact:Increased during GH treatment and remained elevated on day 84 (0.53 → 0.61 kU/L; P < 0.02)
Trust score:5/5

Osteocalcin (bone formation marker)

4 evidences

Exogenous growth hormone increased blood markers of bone and collagen turnover in healthy adults in a dose-dependent manner.

Trust comment: Multicenter, randomized, double-blind, placebo-controlled trial with 99 healthy volunteers and clear biomarker changes.

Study Details

PMID:10770189
Participants:99
Impact:Increased during treatment and remained elevated on day 84 (12.2 → 14.6 µg/L; P < 0.02)
Trust score:5/5

Short randomized trial showing rosiglitazone reduces biochemical markers of bone formation (including a procollagen marker) and decreases hip BMD in postmenopausal women.

Trust comment: Randomized, double‑blind controlled trial with clear biochemical and BMD endpoints but small sample and short duration (14 weeks).

Study Details

PMID:17264176
Participants:50
Impact:↓10% vs placebo (P=0.04)
Trust score:4/5

In ART‑naive HIV patients who completed follow‑up, starting antiretroviral therapy (especially PI‑containing regimens) was associated with early fat mass gain and an early drop in lumbar spine BMD; vitamin D was measured but not an intervention.

Trust comment: Prospective randomized treatment allocation but small analyzable sample (35) with missing follow-up data, so moderate confidence.

Study Details

PMID:23809140
Participants:35
Impact:+70% during follow-up
Trust score:3/5

In Mexican postmenopausal women with osteoporosis, bazedoxifene markedly reduced bone turnover markers including a collagen resorption marker versus placebo at 12 months.

Trust comment: Subgroup analysis of a large randomized trial but small Mexican subgroup reduces power and precision; biochemical endpoints robust though.

Study Details

PMID:27116464
Participants:76
Impact:At 12 months osteocalcin percent change −40.5% (BZA) vs −18.5% (placebo), P<0.001.
Trust score:3/5

Type I procollagen C-terminal propeptide and type I collagen telopeptide

1 evidences

Exogenous growth hormone increased blood markers of bone and collagen turnover in healthy adults in a dose-dependent manner.

Trust comment: Multicenter, randomized, double-blind, placebo-controlled trial with 99 healthy volunteers and clear biomarker changes.

Study Details

PMID:10770189
Participants:99
Impact:Increased on days 21 and 28 during GH but returned toward baseline by day 84
Trust score:5/5

Glycemic control (fasting glucose, HbA1c)

1 evidences

Daily marine collagen peptides (13 g) for 3 months improved blood glucose, lipid profile, and some inflammatory/adipokine markers in patients with type 2 diabetes.

Trust comment: Randomized clinical trial with 100 diabetic patients (plus 50 controls) showing consistent biomarker improvements, though full methodological details are not in the excerpt.

Study Details

PMID:21164551
Participants:150
Impact:Significantly decreased after 1.5 and 3 months of MCP treatment (P < 0.01)
Trust score:4/5

Lipid profile (TG, TC, LDL, HDL, FFAs)

1 evidences

Daily marine collagen peptides (13 g) for 3 months improved blood glucose, lipid profile, and some inflammatory/adipokine markers in patients with type 2 diabetes.

Trust comment: Randomized clinical trial with 100 diabetic patients (plus 50 controls) showing consistent biomarker improvements, though full methodological details are not in the excerpt.

Study Details

PMID:21164551
Participants:150
Impact:TG, TC, LDL, and FFAs decreased; HDL increased after 1.5 and 3 months (P < 0.01)
Trust score:4/5

Inflammation/adipokines (hs-CRP, NO, bradykinin, PGI2, adiponectin)

1 evidences

Daily marine collagen peptides (13 g) for 3 months improved blood glucose, lipid profile, and some inflammatory/adipokine markers in patients with type 2 diabetes.

Trust comment: Randomized clinical trial with 100 diabetic patients (plus 50 controls) showing consistent biomarker improvements, though full methodological details are not in the excerpt.

Study Details

PMID:21164551
Participants:150
Impact:hs-CRP and NO decreased; bradykinin, PGI2, and adiponectin increased (P < 0.01)
Trust score:4/5

Wrinkle augmentation efficacy

1 evidences

Artecoll (PMMA microspheres + bovine collagen) produced greater and longer-lasting wrinkle augmentation and higher satisfaction than standard collagen filler with acceptable safety.

Trust comment: Large randomized multicenter trial with objective and subjective outcomes and extended follow-up, supporting robustness of findings.

Study Details

PMID:15468406
Participants:251
Impact:Artecoll superior to collagen filler at 6 months (p < 0.001)
Trust score:4/5

Investigator and subject satisfaction

1 evidences

Artecoll (PMMA microspheres + bovine collagen) produced greater and longer-lasting wrinkle augmentation and higher satisfaction than standard collagen filler with acceptable safety.

Trust comment: Large randomized multicenter trial with objective and subjective outcomes and extended follow-up, supporting robustness of findings.

Study Details

PMID:15468406
Participants:251
Impact:Higher for Artecoll at 6 months (p < 0.001)
Trust score:4/5

hip BMD

1 evidences

Transdermal estradiol+levonorgestrel increased BMD (lumbar spine, hip, total body) and reduced bone turnover markers over 2 years.

Trust comment: Prospective 2-year study with adequate sample size and consistent biomarker and BMD changes; well-reported safety data.

Study Details

PMID:15653003
Participants:212
Impact:+6% (increase vs placebo; P < 0.001)
Trust score:4/5

bone turnover markers

2 evidences

In osteopenic postmenopausal women receiving calcium/magnesium/calcitriol, red clover extract plus probiotics reduced lumbar spine BMD loss and improved bone turnover and estrogen metabolite profile versus placebo.

Trust comment: 12-month double-blind RCT with 78 participants — well-designed but moderate sample size.

Study Details

PMID:28768651
Participants:78
Impact:improved bone turnover (statistically significant)
Trust score:4/5

PTH therapy increased early collagen-formation markers and larger short-term increases predicted greater spine and hip BMD gains at 1 year.

Trust comment: Large randomized placebo-controlled multicenter trial with objective BMD measures; measures PINP (a collagen formation marker) indirectly related to collagen biology.

Study Details

PMID:16449339
Participants:238
Impact:increased shortly after PTH therapy (1 and 3 months)
Trust score:4/5

clinical responder rate (VAS)

1 evidences

In people ≥50 years with joint pain, 1200 mg/day collagen hydrolysate increased the proportion of clinical responders at 6 months versus placebo.

Trust comment: Large randomized double-blind multicenter trial with ITT analysis; subjective primary outcome and modest effect size, so fairly reliable.

Study Details

PMID:22500661
Participants:200
Impact:Higher responder rate with collagen hydrolysate at 6 months: 51.6% vs 36.5% (difference ≈+15.1 percentage points; p<0.05)
Trust score:4/5

short-term (3 months) responder rate

1 evidences

In people ≥50 years with joint pain, 1200 mg/day collagen hydrolysate increased the proportion of clinical responders at 6 months versus placebo.

Trust comment: Large randomized double-blind multicenter trial with ITT analysis; subjective primary outcome and modest effect size, so fairly reliable.

Study Details

PMID:22500661
Participants:200
Impact:No significant difference at 3 months (44.1% vs 39.6%; p=0.53)
Trust score:4/5

VAS pain

3 evidences

Double‑blind RCT of hydrolyzed chicken type II collagen (2.5 g/day) versus placebo in adults with joint discomfort over 8 weeks; assessed pain, stiffness, and function.

Trust comment: Randomized, double‑blind placebo‑controlled human trial with clinically relevant patient‑reported outcomes but small sample and short follow‑up.

Study Details

PMID:34371963
Participants:90
Impact:AVC‑H2: −44.8% at week 4 vs placebo −32.4% (90% CI significance); week 8: −56.2% vs −42.7% (90% CI significance)
Trust score:4/5

In patients with knee/hip OA, BioCell Collagen (2 g/day) over 70 days reduced pain and improved WOMAC and physical function versus placebo.

Trust comment: Randomized double-blind RCT with validated outcomes but moderate sample size and short duration; findings reasonably credible.

Study Details

PMID:22486722
Participants:80
Impact:Significant reduction in VAS pain at day 70 in treatment vs placebo (p<0.001)
Trust score:4/5

Four weeks of an oral supplement containing hydrolyzed collagen type II plus HA and CS reduced pain scores and decreased some inflammatory cytokines in synovial fluid of knee OA patients.

Trust comment: Pilot randomized study in 30 patients with short (4-week) duration and small sample size, limiting confidence.

Study Details

PMID:33213125
Participants:30
Impact:reduced (p<0.01)
Trust score:3/5

WOMAC score

1 evidences

In patients with knee/hip OA, BioCell Collagen (2 g/day) over 70 days reduced pain and improved WOMAC and physical function versus placebo.

Trust comment: Randomized double-blind RCT with validated outcomes but moderate sample size and short duration; findings reasonably credible.

Study Details

PMID:22486722
Participants:80
Impact:Significant improvement in WOMAC at day 35 (p=0.017) and day 70 (p<0.001) in treatment vs placebo
Trust score:4/5

physical activity/functional improvement

1 evidences

In patients with knee/hip OA, BioCell Collagen (2 g/day) over 70 days reduced pain and improved WOMAC and physical function versus placebo.

Trust comment: Randomized double-blind RCT with validated outcomes but moderate sample size and short duration; findings reasonably credible.

Study Details

PMID:22486722
Participants:80
Impact:Significant improvement in activities on days 35 (p=0.007) and 70 (p<0.001)
Trust score:4/5

Grade A healing rate at ~1 month

1 evidences

In oral soft tissue repair, a gelatin/polycaprolactone membrane was noninferior to a collagen membrane for Grade A healing at 1 month, with similar secondary outcomes and adverse events.

Trust comment: Prospective randomized clinical trial in humans comparing to a collagen membrane; single-blind and moderate sample but appropriate endpoints, so fairly trustworthy.

Study Details

PMID:39955202
Participants:48
Impact:100% Grade A healing in both TRM and collagen membrane groups (rate difference 0%; 95% CI −5% to +5%)
Trust score:4/5

secondary healing outcomes and adverse events

1 evidences

In oral soft tissue repair, a gelatin/polycaprolactone membrane was noninferior to a collagen membrane for Grade A healing at 1 month, with similar secondary outcomes and adverse events.

Trust comment: Prospective randomized clinical trial in humans comparing to a collagen membrane; single-blind and moderate sample but appropriate endpoints, so fairly trustworthy.

Study Details

PMID:39955202
Participants:48
Impact:No significant differences between groups for secondary endpoints or adverse events (P>0.05)
Trust score:4/5

complete hemostasis within 3 min

1 evidences

A collagen fleece (Sangustop) was noninferior to a carrier-bound fibrin sealant for achieving surgical hemostasis after liver resection; safety was similar.

Trust comment: Large multicenter randomized controlled trial with appropriate endpoints and balanced groups, single-blind limitation noted.

Study Details

PMID:24880345
Participants:127
Impact:+6.9% (COLL 86.9% vs CBFS 80.0%)
Trust score:4/5

hemostasis within 10 min

1 evidences

A collagen fleece (Sangustop) was noninferior to a carrier-bound fibrin sealant for achieving surgical hemostasis after liver resection; safety was similar.

Trust comment: Large multicenter randomized controlled trial with appropriate endpoints and balanced groups, single-blind limitation noted.

Study Details

PMID:24880345
Participants:127
Impact:-2.0 percentage points (COLL 98% vs CBFS 100%)
Trust score:4/5

time to hemostasis (mean)

1 evidences

A collagen fleece (Sangustop) was noninferior to a carrier-bound fibrin sealant for achieving surgical hemostasis after liver resection; safety was similar.

Trust comment: Large multicenter randomized controlled trial with appropriate endpoints and balanced groups, single-blind limitation noted.

Study Details

PMID:24880345
Participants:127
Impact:COLL 2.2 min vs CBFS 3.38 min (−1.18 min)
Trust score:4/5

early healing index (EHI)

1 evidences

Placement of a collagen hemostatic sponge in palatal donor sites yielded similar early wound healing, bleeding, and pain whether sutured or not.

Trust comment: Randomized clinical trial with modest sample size showing no significant differences; endpoints clinically relevant but limited power.

Study Details

PMID:33140428
Participants:36
Impact:no difference between sutured and non-sutured groups at 7, 14, 30 days
Trust score:3/5

pain (VAS mean)

1 evidences

Placement of a collagen hemostatic sponge in palatal donor sites yielded similar early wound healing, bleeding, and pain whether sutured or not.

Trust comment: Randomized clinical trial with modest sample size showing no significant differences; endpoints clinically relevant but limited power.

Study Details

PMID:33140428
Participants:36
Impact:SG 36.2 vs nSG 21.5 (mean difference −14.7 points), P>0.05
Trust score:3/5

immediate bleeding (counts)

1 evidences

Placement of a collagen hemostatic sponge in palatal donor sites yielded similar early wound healing, bleeding, and pain whether sutured or not.

Trust comment: Randomized clinical trial with modest sample size showing no significant differences; endpoints clinically relevant but limited power.

Study Details

PMID:33140428
Participants:36
Impact:SG 4 vs nSG 3 (no significant difference)
Trust score:3/5

analgesic consumption (pills)

1 evidences

Using different wound dressings (including a collagen plug control) after palatal graft harvest changed pain and painkiller use; stents and biologic dressings reduced pain and analgesic use.

Trust comment: Good-quality randomized controlled trial with adequate sample (n=72), 100% retention, and appropriate analyses.

Study Details

PMID:35754198
Participants:72
Impact:Median pills: CPS 21.5 → CPC 15 (-6.5, -30%), PRF 11.5 (-10, -46.5%), PS 7.5 (-14, -65.1%); test groups consumed significantly fewer analgesics vs CPS (P<0.0001)
Trust score:5/5

willingness for retreatment

1 evidences

Using different wound dressings (including a collagen plug control) after palatal graft harvest changed pain and painkiller use; stents and biologic dressings reduced pain and analgesic use.

Trust comment: Good-quality randomized controlled trial with adequate sample (n=72), 100% retention, and appropriate analyses.

Study Details

PMID:35754198
Participants:72
Impact:Median willingness score: CPS 3 → CPC 6 (+3), PRF 6.5 (+3.5), PS 8.5 (+5.5); test groups significantly more willing vs CPS (P<0.001)
Trust score:5/5

parathyroid hormone (PTH)

3 evidences

Randomized trial in 120 children (9–12 y): a protein-rich multi-nutrient drink plus rope-skipping attenuated seasonal forearm BMD loss vs rope-skipping alone and modulated PTH and IGF-1 changes.

Trust comment: Randomized controlled trial in children with clear effects on BMD and serum markers, but intervention combined multiple proteins including collagen peptides so effects cannot be attributed specifically to collagen.

Study Details

PMID:39991811
Participants:120
Impact:-8.53 ng L^-1 (relative change; smaller increase vs control, P=0.012)
Trust score:3/5

Single 1000 mg calcium dose from milk or calcium carbonate acutely reduced bone resorption (CTX-1) and lowered PTH in postmenopausal women regardless of visceral fat.

Trust comment: Randomized three-period crossover in 77 postmenopausal women with frequent timed sampling; robust design for acute effects.

Study Details

PMID:36967157
Participants:77
Impact:-47% with calcium carbonate; -22% with milk
Trust score:4/5

Drinking bicarbonate-rich (alkaline) mineral water for 2–4 weeks reduced serum CTX and PTH compared with an acidic calcium-rich water in young women.

Trust comment: Small randomized dietary intervention with short duration and biochemical endpoints; informative but limited generalizability.

Study Details

PMID:18926940
Participants:30
Impact:decrease with alkaline water (p=0.022)
Trust score:3/5

wrinkle severity (Wrinkle Assessment Scale)

1 evidences

Human-derived collagen injections improved nasolabial wrinkles, but improvements were smaller and less durable than with injectable PLLA.

Trust comment: Randomized, evaluator-blinded multicenter trial with large sample but comparator favored PLLA; outcomes clinically measured.

Study Details

PMID:20159311
Participants:233
Impact:Collagen injections produced improvement, but PLLA produced significantly greater and longer-lasting improvements (PLLA > collagen at months 3–13; PLLA durable up to 25 months)
Trust score:4/5

ICTP (type I collagen telopeptide)

2 evidences

In a randomized study of 47 hips, two bone cements showed similar clinical performance; collagen‑related bone turnover markers (PICP, ICTP) rose similarly after surgery at 6 weeks and 6 months.

Trust comment: Randomized clinical comparison with 5‑year follow‑up; biomarker changes reported but magnitude not fully specified in provided text.

Study Details

PMID:11817871
Participants:47
Impact:Increase at 6 weeks and 6 months after operation (magnitude not specified) vs baseline
Trust score:3/5

Study of postmenopausal RA patients (both groups received vitamin D3 and calcium) found resistin associated with markers of inflammation and reduced BMD; HRT transiently increased resistin in year 1.

Trust comment: Randomized allocation to HRT vs control with validated biomarker assays and 2-year follow-up, but findings are associative.

Study Details

PMID:18511473
Participants:88
Impact:positively correlated with resistin (association with bone resorption)
Trust score:4/5

Clinical attachment level (CAL) gain

7 evidences

Minimally invasive periodontal surgery produced clinical attachment gains at 1 year; adding deproteinized bovine bone mineral plus a collagen membrane did not improve 1-year outcomes versus surgery alone.

Trust comment: Randomized trial directly tested a collagen-containing membrane as a regenerative material; small sample size limits certainty but design is appropriate.

Study Details

PMID:34414521
Participants:31
Impact:MISTms-alone +2.53 ±1.80 mm; MISTms+regenerative materials +2.00 ±1.38 mm (no significant difference between groups)
Trust score:3/5

In combined surgical therapy of peri-implantitis with bone graft and collagen membrane, the choice of debridement/decontamination method (Er:YAG laser vs curets+saline) did not significantly affect 6-month clinical or radiographic outcomes.

Trust comment: Randomized controlled clinical study on humans with objective clinical and radiographic measures, but small sample and short follow-up limit generalizability.

Study Details

PMID:21219392
Participants:30
Impact:ERL 1.5±1.4 mm vs CPS 2.2±1.4 mm (no significant difference)
Trust score:4/5

Use of a collagen membrane with bovine bone graft improved periodontal pocket depth and attachment over 12 months compared with flap procedure alone.

Trust comment: Prospective randomized controlled clinical trial with 12-month follow-up; moderate sample size and clinically relevant endpoints.

Study Details

PMID:15367197
Participants:34
Impact:+4.39 mm (collagen-BBM group, 12 months)
Trust score:4/5

Adding anorganic bovine bone to a collagen membrane (CPRT) produced greater attachment gains and more vertical bone gain than collagen membrane alone after 1 year.

Trust comment: Randomized controlled study with clear clinical and surgical endpoints gives moderate-high trust.

Study Details

PMID:11895280
Participants:34
Impact:greater CAL gain in CPRT test group versus collagen membrane alone (P<0.05)
Trust score:4/5

Adding autogenous bone (with or without bioactive glass) to a collagen membrane led to greater periodontal defect healing than collagen membrane alone.

Trust comment: Randomized treatment of 32 defects in 22 subjects; small sample but randomized and clinically relevant outcomes.

Study Details

PMID:22167034
Participants:22
Impact:Significant gain in all groups with greater improvement in test groups
Trust score:3/5

L-PRF+IBB was non-inferior to collagen membrane+IBB for clinical attachment gain and produced less gingival recession, though it had slightly less probing-depth reduction.

Trust comment: Randomized non-inferiority trial with balanced groups and 12-month follow-up; results reported with CIs.

Study Details

PMID:33547808
Participants:62
Impact:+0.81 mm (CM+IBB - L-PRF+IBB = -0.810 mm, favoring L-PRF+IBB)
Trust score:4/5

In periodontal defects, GTR using collagen membranes and autogenous periosteal+bone chip treatment both improved probing depth, attachment level, and bone defect fill more than debridement alone; autogenous periosteal approach gave greatest bone gain.

Trust comment: Randomized controlled clinical trial with objective surgical re-entry measurements and clear numerical outcomes; directly evaluates collagen membranes.

Study Details

PMID:20583915
Participants:42
Impact:GTR: 3.2 mm; aCPRT: 3.9 mm; OFD: 1.6 mm (1 year)
Trust score:4/5

glycemic control (FBG, HbA1c)

1 evidences

Marine collagen peptide supplementation for 3 months improved glucose control, lipids, insulin sensitivity, and some renal and inflammatory markers in patients with T2DM and hypertension.

Trust comment: Randomized double-blind trial with 100 patients (50 per arm) showing multiple metabolic improvements; moderate sample and limited to specific population restricts broad generalizability.

Study Details

PMID:20739874
Participants:150
Impact:Significant reductions in fasting blood glucose and HbA1c vs patient controls after 3 months
Trust score:4/5

lipid profile

1 evidences

Marine collagen peptide supplementation for 3 months improved glucose control, lipids, insulin sensitivity, and some renal and inflammatory markers in patients with T2DM and hypertension.

Trust comment: Randomized double-blind trial with 100 patients (50 per arm) showing multiple metabolic improvements; moderate sample and limited to specific population restricts broad generalizability.

Study Details

PMID:20739874
Participants:150
Impact:Significant reductions in triglycerides, total cholesterol, LDL and free fatty acids; HDL increased in MCP group vs controls
Trust score:4/5

insulin sensitivity and secretion

1 evidences

Marine collagen peptide supplementation for 3 months improved glucose control, lipids, insulin sensitivity, and some renal and inflammatory markers in patients with T2DM and hypertension.

Trust comment: Randomized double-blind trial with 100 patients (50 per arm) showing multiple metabolic improvements; moderate sample and limited to specific population restricts broad generalizability.

Study Details

PMID:20739874
Participants:150
Impact:Insulin Sensitivity Index and Insulin Secretion Index increased significantly in MCP-treated patients
Trust score:4/5

clinical cure & improvement

1 evidences

In 88 patients with moderate or severe diabetic foot infections, adding a topical gentamicin-collagen sponge to systemic antibiotics did not significantly change overall clinical cure/improvement or pathogen eradication versus systemic antibiotics alone.

Trust comment: Randomized, investigator-blinded controlled trial but single-center and stopped early (underpowered), which limits certainty.

Study Details

PMID:30068306
Participants:88
Impact:no significant difference: gentamicin-sponge 31/43 (88%) vs control 39/45 (87%)
Trust score:4/5

pathogen eradication

1 evidences

In 88 patients with moderate or severe diabetic foot infections, adding a topical gentamicin-collagen sponge to systemic antibiotics did not significantly change overall clinical cure/improvement or pathogen eradication versus systemic antibiotics alone.

Trust comment: Randomized, investigator-blinded controlled trial but single-center and stopped early (underpowered), which limits certainty.

Study Details

PMID:30068306
Participants:88
Impact:no significant difference: gentamicin-sponge 20/45 vs control 26/43 (P = 0.13)
Trust score:4/5

wound healing speed (wound score decline)

1 evidences

In 88 patients with moderate or severe diabetic foot infections, adding a topical gentamicin-collagen sponge to systemic antibiotics did not significantly change overall clinical cure/improvement or pathogen eradication versus systemic antibiotics alone.

Trust comment: Randomized, investigator-blinded controlled trial but single-center and stopped early (underpowered), which limits certainty.

Study Details

PMID:30068306
Participants:88
Impact:trend toward faster wound score decrease with sponge during weeks 3–5 (not statistically significant)
Trust score:4/5

insulin-like growth factor-1 (IGF-1)

1 evidences

Randomized trial in 120 children (9–12 y): a protein-rich multi-nutrient drink plus rope-skipping attenuated seasonal forearm BMD loss vs rope-skipping alone and modulated PTH and IGF-1 changes.

Trust comment: Randomized controlled trial in children with clear effects on BMD and serum markers, but intervention combined multiple proteins including collagen peptides so effects cannot be attributed specifically to collagen.

Study Details

PMID:39991811
Participants:120
Impact:+20.75 ng mL^-1 (relative change; smaller decrease vs control, P=0.076)
Trust score:3/5

urine N-telopeptide (NTx)

1 evidences

Multicenter randomized trial of once-weekly alendronate in postmenopausal Chinese women; not designed to test Vitamin D effects.

Trust comment: Large randomized double-blind placebo-controlled multicenter trial (n=560) with objective BMD and bone turnover endpoints; high reliability.

Study Details

PMID:19343272
Participants:560
Impact:decrease (significant at 6 months)
Trust score:4/5

urinary N-telopeptide (NTX)

1 evidences

Urinary NTx tracked antiresorptive effects of HRT and predicted subsequent changes in lumbar and hip BMD in recently postmenopausal women.

Trust comment: Randomized controlled 2-year study with 227 completers and clinically meaningful biomarker and BMD endpoints.

Study Details

PMID:9209198
Participants:227
Impact:change in NTx predicted BMD change; high baseline NTx associated with 17.3-fold higher risk of BMD loss if not treated
Trust score:5/5

wrinkle severity (Modified Fitzpatrick Wrinkle Scale)

1 evidences

Randomized multicenter split-face trial comparing porcine collagen filler (Dermicol-P35) with NASHA; both improved nasolabial fold scores with similar durability at 6 months.

Trust comment: Randomized multicenter trial with substantial sample size and 6-month follow-up showing equivalent efficacy; appropriate for evaluating a collagen-derived filler.

Study Details

PMID:18086061
Participants:149
Impact:improved for both: Dermicol +0.39 and NASHA +0.37 at 6 months (no significant difference, p=0.626)
Trust score:4/5

adverse events — swelling/bruising/pain

1 evidences

Randomized multicenter split-face trial comparing porcine collagen filler (Dermicol-P35) with NASHA; both improved nasolabial fold scores with similar durability at 6 months.

Trust comment: Randomized multicenter trial with substantial sample size and 6-month follow-up showing equivalent efficacy; appropriate for evaluating a collagen-derived filler.

Study Details

PMID:18086061
Participants:149
Impact:more frequent at NASHA-treated sites (reported by greater proportion of subjects)
Trust score:4/5

extrusion of obturating material

1 evidences

Randomized clinical trial placing a resorbable collagen barrier in canals of resorbing primary molars; test group had fewer extrusions but the difference was not statistically significant.

Trust comment: Randomized clinical dental trial using a collagen barrier; small sample and non-significant difference reduce confidence in efficacy despite randomized design.

Study Details

PMID:34740265
Participants:47
Impact:test (collagen barrier) extrusion 6.4% vs control 17% (93.6% vs 83% no extrusion), difference not statistically significant (p>0.05)
Trust score:3/5

Bifidobacterium concentration

1 evidences

In adults with major burns, two weeks of hydrolyzed collagen (with or without fish oil) altered some gut bacterial measures; adding omega-3 prevented loss of Bifidobacterium but overall between-group differences were not significant.

Trust comment: Randomized double-blind trial but small sample, short (2‑week) intervention and surrogate microbiome endpoints limit generalizability.

Study Details

PMID:38114377
Participants:57
Impact:Significant decrease vs baseline with collagen alone; no significant change with collagen+omega-3 (omega-3 prevented decrease)
Trust score:3/5

Firmicutes:Bacteroidetes ratio

1 evidences

In adults with major burns, two weeks of hydrolyzed collagen (with or without fish oil) altered some gut bacterial measures; adding omega-3 prevented loss of Bifidobacterium but overall between-group differences were not significant.

Trust comment: Randomized double-blind trial but small sample, short (2‑week) intervention and surrogate microbiome endpoints limit generalizability.

Study Details

PMID:38114377
Participants:57
Impact:Significant decrease vs baseline with collagen group
Trust score:3/5

Lactobacillus concentration

1 evidences

In adults with major burns, two weeks of hydrolyzed collagen (with or without fish oil) altered some gut bacterial measures; adding omega-3 prevented loss of Bifidobacterium but overall between-group differences were not significant.

Trust comment: Randomized double-blind trial but small sample, short (2‑week) intervention and surrogate microbiome endpoints limit generalizability.

Study Details

PMID:38114377
Participants:57
Impact:No significant change between or within groups
Trust score:3/5

Indices of muscle damage (e.g., creatine kinase)

1 evidences

In young fit males undergoing eccentric training, replacing part of whey with collagen peptides (20 g) produced no additional benefit versus whey alone for muscle damage markers or recovery of function.

Trust comment: Randomized double-blind trial but small sample (n=22) and short training period limit power to detect modest effects.

Study Details

PMID:37922892
Participants:22
Impact:CK doubled after exercise in both groups; no between-group difference (no benefit of added collagen)
Trust score:3/5

Functional capacity (maximal voluntary contraction, countermovement jump)

1 evidences

In young fit males undergoing eccentric training, replacing part of whey with collagen peptides (20 g) produced no additional benefit versus whey alone for muscle damage markers or recovery of function.

Trust comment: Randomized double-blind trial but small sample (n=22) and short training period limit power to detect modest effects.

Study Details

PMID:37922892
Participants:22
Impact:Transient ~10% impairment after first session; training improved jump ~8% and MVC ~10% with no between-group difference
Trust score:3/5

Serum procollagen type 1 N‑terminal peptide

1 evidences

In young fit males undergoing eccentric training, replacing part of whey with collagen peptides (20 g) produced no additional benefit versus whey alone for muscle damage markers or recovery of function.

Trust comment: Randomized double-blind trial but small sample (n=22) and short training period limit power to detect modest effects.

Study Details

PMID:37922892
Participants:22
Impact:Increased ~10% with training (no difference between supplement groups)
Trust score:3/5

Intraocular pressure (IOP) at 2 years

1 evidences

In patients with cataract and open‑angle glaucoma, adding a biodegradable collagen‑GAG (Ologen) implant to phaco‑viscocanalostomy produced greater long‑term IOP reduction and higher complete success rates than surgery without the implant.

Trust comment: Randomized trial with moderate sample size and 2‑year follow-up; results are clinically relevant though single‑center and surgical technique may limit broad generalizability.

Study Details

PMID:30727982
Participants:79
Impact:Lower in Ologen group (mean 15.96 mmHg) vs control (16.85 mmHg); p=0.02
Trust score:4/5

Complete success rate (IOP ≤21 mmHg without medications)

1 evidences

In patients with cataract and open‑angle glaucoma, adding a biodegradable collagen‑GAG (Ologen) implant to phaco‑viscocanalostomy produced greater long‑term IOP reduction and higher complete success rates than surgery without the implant.

Trust comment: Randomized trial with moderate sample size and 2‑year follow-up; results are clinically relevant though single‑center and surgical technique may limit broad generalizability.

Study Details

PMID:30727982
Participants:79
Impact:Higher with Ologen (80.0% vs 59.0%; p=0.04)
Trust score:4/5

Nd:YAG goniopuncture parameters (number of laser shots / IOP reduction)

1 evidences

In patients with cataract and open‑angle glaucoma, adding a biodegradable collagen‑GAG (Ologen) implant to phaco‑viscocanalostomy produced greater long‑term IOP reduction and higher complete success rates than surgery without the implant.

Trust comment: Randomized trial with moderate sample size and 2‑year follow-up; results are clinically relevant though single‑center and surgical technique may limit broad generalizability.

Study Details

PMID:30727982
Participants:79
Impact:Fewer laser shots needed and greater post‑goniopuncture IOP reduction in Ologen group (mean shots 5.23 vs 11.47; p<0.001)
Trust score:4/5

Early wound score improvement (2 weeks)

1 evidences

Activated collagen (and PRP) produced early wound-score improvements, less blood loss, and fewer complications in high‑risk patients after joint arthroplasty.

Trust comment: Randomized controlled trial with 30 patients per arm showing clinically relevant outcomes, but moderate sample size and short follow-up limit certainty.

Study Details

PMID:29451945
Participants:90
Impact:Improved in 3 of 6 wound scores at 2 weeks (not sustained at 6 weeks)
Trust score:3/5

Postoperative blood loss

1 evidences

Activated collagen (and PRP) produced early wound-score improvements, less blood loss, and fewer complications in high‑risk patients after joint arthroplasty.

Trust comment: Randomized controlled trial with 30 patients per arm showing clinically relevant outcomes, but moderate sample size and short follow-up limit certainty.

Study Details

PMID:29451945
Participants:90
Impact:Reduced (statistically significant vs control)
Trust score:3/5

Total complication rate in high‑risk patients

1 evidences

Activated collagen (and PRP) produced early wound-score improvements, less blood loss, and fewer complications in high‑risk patients after joint arthroplasty.

Trust comment: Randomized controlled trial with 30 patients per arm showing clinically relevant outcomes, but moderate sample size and short follow-up limit certainty.

Study Details

PMID:29451945
Participants:90
Impact:Reduced (statistically significant vs control)
Trust score:3/5

Gingival recession reduction

1 evidences

Adding a porcine collagen matrix to coronally advanced flap surgery produced similar root coverage but a small increase in soft tissue thickness at 6 months.

Trust comment: Randomized clinical trial with clear clinical endpoints and statistically reported results, providing moderate-to-high confidence.

Study Details

PMID:26917493
Participants:40
Impact:Significant in both groups; no superior reduction with collagen matrix (p > 0.05)
Trust score:4/5

Root coverage percentage

2 evidences

In a split-mouth RCT, xenogeneic collagen matrix (XCM) improved root coverage and quality of life but CTG produced greater final gingival thickness and slightly better root-coverage metrics at 18 months.

Trust comment: Split-mouth, double-blind RCT with 18-month follow-up; moderate sample size but rigorous design supports moderate-high trust.

Study Details

PMID:39536202
Participants:30
Impact:Average RC: XCM 72.9% vs CTG 88.9% (no statistically significant difference between groups)
Trust score:4/5

Adding a porcine collagen matrix to coronally advanced flap surgery produced similar root coverage but a small increase in soft tissue thickness at 6 months.

Trust comment: Randomized clinical trial with clear clinical endpoints and statistically reported results, providing moderate-to-high confidence.

Study Details

PMID:26917493
Participants:40
Impact:CAF + CM 77.2% vs CAF 72.1% (p > 0.05)
Trust score:4/5

Keratinized tissue thickness

1 evidences

Adding a porcine collagen matrix to coronally advanced flap surgery produced similar root coverage but a small increase in soft tissue thickness at 6 months.

Trust comment: Randomized clinical trial with clear clinical endpoints and statistically reported results, providing moderate-to-high confidence.

Study Details

PMID:26917493
Participants:40
Impact:+0.26 mm in CAF + CM (p < 0.05)
Trust score:4/5

root coverage

3 evidences

Using a collagen matrix with a flap slightly increased gum thickness and keratinized tissue but did not significantly improve overall root coverage at 6 months.

Trust comment: Multicentre randomized split-mouth trial with clear outcomes and statistical tests; moderate sample size (45 patients).

Study Details

PMID:23050490
Participants:45
Impact:75.29% (CAF+CM) vs 72.66% (CAF alone); p=0.169
Trust score:4/5

Split-mouth randomized trial comparing rhPDGF-BB + beta-TCP + bioabsorbable collagen dressing versus connective tissue graft for gingival recession; both improved clinically, with some measures favoring CTG and others favoring the test.

Trust comment: Well-designed split-mouth RCT with histologic corroboration but modest sample size; reliable within its surgical context.

Study Details

PMID:19335074
Participants:30
Impact:test 90.8% vs control 98.6% (P=0.013 favoring control)
Trust score:4/5

Adding a xenogeneic collagen matrix to coronally advanced flap surgery increased keratinized tissue width and gingival thickness vs flap alone, while root coverage and patient satisfaction were similar at 12 months.

Trust comment: Randomized controlled trial with 45 patients and objective clinical measures; moderate sample size limits power for some outcomes.

Study Details

PMID:27717210
Participants:45
Impact:76.28% (test) vs 75.05% (control); no significant difference
Trust score:4/5

keratinized tissue width increase

1 evidences

Using a collagen matrix with a flap slightly increased gum thickness and keratinized tissue but did not significantly improve overall root coverage at 6 months.

Trust comment: Multicentre randomized split-mouth trial with clear outcomes and statistical tests; moderate sample size (45 patients).

Study Details

PMID:23050490
Participants:45
Impact:+0.93 mm (test) vs +0.57 mm (control); p=0.036
Trust score:4/5

gingival thickness gain

2 evidences

Using a collagen matrix with a flap slightly increased gum thickness and keratinized tissue but did not significantly improve overall root coverage at 6 months.

Trust comment: Multicentre randomized split-mouth trial with clear outcomes and statistical tests; moderate sample size (45 patients).

Study Details

PMID:23050490
Participants:45
Impact:+0.59 mm (test) vs +0.34 mm (control); p=0.003
Trust score:4/5

Adding a collagen matrix or an acellular dermal matrix to a coronally advanced flap gave similar root coverage; both matrices increased gingival thickness more than flap alone.

Trust comment: Randomized clinical trial with 75 completers and 6-month follow-up, providing reasonably reliable clinical outcomes.

Study Details

PMID:34598314
Participants:75
Impact:+0.4 ± 0.3 mm (CAF+CM) and +0.4 ± 0.2 mm (CAF+XDM) vs +0.0 ± 0.1 mm (CAF); P<0.05
Trust score:4/5

horizontal bone width after 6 months

1 evidences

Comparing CGF membrane (sticky bone) to native collagen membrane showed no significant difference in horizontal bone gain at 6 months; CGF membrane was less predictable clinically.

Trust comment: Randomized clinical trial but small sample (28 patients) and some graft failures reported, limiting predictability.

Study Details

PMID:35811435
Participants:28
Impact:9.0 ± 0.71 mm (GBR with native collagen membrane) vs 7.9 ± 0.92 mm (sticky bone with CGF)
Trust score:3/5

primary implant stability (ISQ)

1 evidences

Comparing CGF membrane (sticky bone) to native collagen membrane showed no significant difference in horizontal bone gain at 6 months; CGF membrane was less predictable clinically.

Trust comment: Randomized clinical trial but small sample (28 patients) and some graft failures reported, limiting predictability.

Study Details

PMID:35811435
Participants:28
Impact:67.19 ± 2.23 (GBR) vs 66.7 ± 3.22 (sticky bone)
Trust score:3/5

secondary implant stability (ISQ)

1 evidences

Comparing CGF membrane (sticky bone) to native collagen membrane showed no significant difference in horizontal bone gain at 6 months; CGF membrane was less predictable clinically.

Trust comment: Randomized clinical trial but small sample (28 patients) and some graft failures reported, limiting predictability.

Study Details

PMID:35811435
Participants:28
Impact:71.7 ± 2.27 (GBR) vs 72.0 ± 2.15 (sticky bone)
Trust score:3/5

PRO-C3 (collagen type-3 synthesis marker)

1 evidences

Blood biomarkers of collagen type-3 and type-6 synthesis were higher in IPF patients and were consistently higher in patients with progressive disease; some degradation markers predicted mortality.

Trust comment: Prospective multicentre cohort with standardized sampling and longitudinal follow-up (145 IPF patients), rigorous biomarker assays and survival analyses.

Study Details

PMID:31299951
Participants:145
Impact:Elevated in IPF vs controls; higher in progressive vs stable disease; unadjusted HR for mortality 1.49 per 2-fold increase (p=0.030)
Trust score:4/5

PRO-C6 (collagen type-6 synthesis marker)

1 evidences

Blood biomarkers of collagen type-3 and type-6 synthesis were higher in IPF patients and were consistently higher in patients with progressive disease; some degradation markers predicted mortality.

Trust comment: Prospective multicentre cohort with standardized sampling and longitudinal follow-up (145 IPF patients), rigorous biomarker assays and survival analyses.

Study Details

PMID:31299951
Participants:145
Impact:Elevated in IPF vs controls and higher in progressive disease across visits
Trust score:4/5

P1NP (collagen type-1 synthesis marker)

1 evidences

Blood biomarkers of collagen type-3 and type-6 synthesis were higher in IPF patients and were consistently higher in patients with progressive disease; some degradation markers predicted mortality.

Trust comment: Prospective multicentre cohort with standardized sampling and longitudinal follow-up (145 IPF patients), rigorous biomarker assays and survival analyses.

Study Details

PMID:31299951
Participants:145
Impact:No significant elevation between IPF and controls or between progressive and stable disease
Trust score:4/5

relative clinical attachment level (R-CAL) gain

1 evidences

Both PRF and PLA-PGA membranes combined with hydroxyapatite crystal collagen-fiber graft led to significant defect improvement at 6 months, with no significant difference between membranes.

Trust comment: Randomized parallel design but small sample (28 patients) and short follow-up (6 months) limit robustness.

Study Details

PMID:37622620
Participants:28
Impact:Significant within-group gains; between-group difference not significant (mean difference 0.28 ± 1.85 mm)
Trust score:3/5

radiographic defect depth reduction

1 evidences

Both PRF and PLA-PGA membranes combined with hydroxyapatite crystal collagen-fiber graft led to significant defect improvement at 6 months, with no significant difference between membranes.

Trust comment: Randomized parallel design but small sample (28 patients) and short follow-up (6 months) limit robustness.

Study Details

PMID:37622620
Participants:28
Impact:Significant within-group reductions; between-group difference not significant (mean difference 0.12 ± 1.42 mm)
Trust score:3/5

PIIINP (N-terminal propeptide of procollagen type III)

1 evidences

Spironolactone treatment was associated with reductions in serum collagen synthesis biomarkers (notably PICP and, in some analyses, PIIINP), suggesting reduced myocardial collagen synthesis.

Trust comment: Non-randomized add-on treatment with propensity matching and within-person analyses (moderate sample size), providing moderate-quality evidence on biomarkers.

Study Details

PMID:30121630
Participants:173
Impact:Between-person adjusted means: +0.52 ng/mL (controls) vs -0.41 ng/mL (spironolactone); p=0.031; within-person change not significant
Trust score:3/5

PICP (C-terminal propeptide of procollagen type I)

1 evidences

Spironolactone treatment was associated with reductions in serum collagen synthesis biomarkers (notably PICP and, in some analyses, PIIINP), suggesting reduced myocardial collagen synthesis.

Trust comment: Non-randomized add-on treatment with propensity matching and within-person analyses (moderate sample size), providing moderate-quality evidence on biomarkers.

Study Details

PMID:30121630
Participants:173
Impact:Between-person: +4.54 ng/mL (controls) vs -6.36 ng/mL (spironolactone); p=0.023; within-person beta = -11.82 ng/mL (p<0.001)
Trust score:3/5

recession reduction / root coverage

1 evidences

Adding a collagen matrix or an acellular dermal matrix to a coronally advanced flap gave similar root coverage; both matrices increased gingival thickness more than flap alone.

Trust comment: Randomized clinical trial with 75 completers and 6-month follow-up, providing reasonably reliable clinical outcomes.

Study Details

PMID:34598314
Participants:75
Impact:Mean root coverage: 78.9% (CAF), 78.0% (CAF+CM), 65.6% (CAF+XDM); no significant differences between groups
Trust score:4/5

dentin hypersensitivity / esthetic improvement

1 evidences

Adding a collagen matrix or an acellular dermal matrix to a coronally advanced flap gave similar root coverage; both matrices increased gingival thickness more than flap alone.

Trust comment: Randomized clinical trial with 75 completers and 6-month follow-up, providing reasonably reliable clinical outcomes.

Study Details

PMID:34598314
Participants:75
Impact:Significant improvements in all groups (no between-group difference reported)
Trust score:4/5

Blood transfusion requirement

1 evidences

Adding a collagen/thrombin hemostatic agent during knee replacement reduced the need for blood transfusion compared with standard care.

Trust comment: Prospective, double-blind randomized design with clinically meaningful outcome though single-center and moderate size.

Study Details

PMID:22035976
Participants:100
Impact:reduced (treatment: 0 transfusions vs control: 5 transfusions; P = 0.007)
Trust score:4/5

VISA score (pain and function)

1 evidences

Injection of lab-expanded, skin-derived collagen-producing cells improved pain and function (VISA score) faster and more than plasma alone in refractory patellar tendinopathy.

Trust comment: Randomized controlled trial (level 1) with clear clinical benefit measures, though single-condition and moderate sample.

Study Details

PMID:21139155
Participants:46
Impact:cell group improved from 44±15 to 75±17 vs plasma 50±18 to 70±14; between-group difference ≈ +8.1 points favoring cells
Trust score:4/5

Speed of clinical improvement

1 evidences

Injection of lab-expanded, skin-derived collagen-producing cells improved pain and function (VISA score) faster and more than plasma alone in refractory patellar tendinopathy.

Trust comment: Randomized controlled trial (level 1) with clear clinical benefit measures, though single-condition and moderate sample.

Study Details

PMID:21139155
Participants:46
Impact:faster improvement in cell-treated group (significant time×treatment effect)
Trust score:4/5

HSP47+ dermal fibroblast number

1 evidences

Split-face randomized trial in older women showed microneedle radiofrequency increased non-senescent fibroblasts and procollagen, reduced senescent fibroblasts, and produced greater improvements in wrinkles, elasticity and hydration versus microneedling alone.

Trust comment: Prospective double-blind split-face RCT with paired histology and multiple objective measures, though single-center and limited follow-up.

Study Details

PMID:40419589
Participants:29
Impact:substantial increase on MNRF side vs MN (n=25 histology, p<0.01)
Trust score:4/5

p16INK4A+ senescent fibroblasts

1 evidences

Split-face randomized trial in older women showed microneedle radiofrequency increased non-senescent fibroblasts and procollagen, reduced senescent fibroblasts, and produced greater improvements in wrinkles, elasticity and hydration versus microneedling alone.

Trust comment: Prospective double-blind split-face RCT with paired histology and multiple objective measures, though single-center and limited follow-up.

Study Details

PMID:40419589
Participants:29
Impact:significant decrease on MNRF side (p<0.001 to p<0.0001)
Trust score:4/5

Procollagen-1 / dermal collagen deposition

1 evidences

Split-face randomized trial in older women showed microneedle radiofrequency increased non-senescent fibroblasts and procollagen, reduced senescent fibroblasts, and produced greater improvements in wrinkles, elasticity and hydration versus microneedling alone.

Trust comment: Prospective double-blind split-face RCT with paired histology and multiple objective measures, though single-center and limited follow-up.

Study Details

PMID:40419589
Participants:29
Impact:notable increase in papillary dermis after MNRF (significant)
Trust score:4/5

Patellar tendon stiffness (mechanical property)

1 evidences

In older adults, 12 months heavy resistance training increased patellar tendon stiffness and preserved material properties compared with moderate/no training; tendon cross-sectional area increased with both training loads, but collagen content and cross-links did not change.

Trust comment: Well-characterized randomized nested sub-study with rigorous mechanical, imaging, biopsy and biochemical measures and adequate completion (n=33).

Study Details

PMID:30704412
Participants:33
Impact:increased with heavy resistance training (e.g., maximal stiffness HRT 4060→4420 N/mm; common-force stiffness +6% after HRT)
Trust score:5/5

Tendon collagen content and cross-links (enzymatic and AGE)

1 evidences

In older adults, 12 months heavy resistance training increased patellar tendon stiffness and preserved material properties compared with moderate/no training; tendon cross-sectional area increased with both training loads, but collagen content and cross-links did not change.

Trust comment: Well-characterized randomized nested sub-study with rigorous mechanical, imaging, biopsy and biochemical measures and adequate completion (n=33).

Study Details

PMID:30704412
Participants:33
Impact:no significant change after 12 months
Trust score:5/5

Corneal densitometry (haze)

2 evidences

Measured corneal haze after transepithelial corneal collagen cross-linking in keratoconus; haze rose transiently and returned to baseline by one year.

Trust comment: Objective densitometry measures in a randomized treatment-timing design with adequate follow-up; moderate-high reliability.

Study Details

PMID:32282356
Participants:43
Impact:mean 20.45 → 22.58 at 1 month (+~10.4%), plateau to 3 months, returned near baseline by 12 months (20.80)
Trust score:4/5

After corneal collagen crosslinking, transient central corneal haze peaked at 1 month and returned to baseline by 6 months.

Trust comment: Prospective randomized controlled design with objective densitometry measures but small sample size.

Study Details

PMID:27492105
Participants:36
Impact:peaked at 1 month post-op and decreased to baseline by 6 months; significant vs untreated eye (P < .01)
Trust score:4/5

Corrected distance visual acuity (CDVA)

11 evidences

Transepithelial (epi-on) CXL in keratoconus produced a small but statistically significant flattening of maximum K (−0.9 D) and improved CDVA at 6 months in this small cohort.

Trust comment: Prospective clinical trial with small sample and short (6-month) follow-up; results suggest short-term benefit but limited durability data.

Study Details

PMID:25465683
Participants:25
Impact:Mean improvement of 0.83 Snellen lines at 6 months (P=0.03)
Trust score:3/5

Using donor corneas pretreated with corneal collagen cross-linking led to better visual acuity and less myopia/astigmatism after penetrating keratoplasty over 3 years.

Trust comment: Well-powered randomized controlled trial (n=116) with 3‑year follow-up showing consistent improvements in visual and topographic outcomes.

Study Details

PMID:29032110
Participants:116
Impact:Improved by 0.06 logMAR (0.17 ±0.10 vs 0.23 ±0.12 logMAR; P=0.004)
Trust score:4/5

Corneal collagen crosslinking improved vision and corneal curvature over one year versus sham (riboflavin alone), with many patients gaining lines of vision and mean K values decreasing.

Trust comment: Prospective randomized controlled trial with a sham control and reasonable sample size; well-reported clinical outcomes.

Study Details

PMID:21183110
Participants:71
Impact:improved from 0.35 to 0.23 logMAR (P < .001); 21.1% gained ≥2 Snellen lines, 1.4% lost ≥2 lines
Trust score:4/5

Two corneal cross-linking procedures stabilized keratoconus over 12 months with modest differences; iontophoresis transepithelial treatment gave significant visual gains but slightly less corneal flattening than standard protocol.

Trust comment: Prospective randomized controlled trial with 12‑month follow-up but modest sample size (34 eyes, 25 patients).

Study Details

PMID:28283279
Participants:25
Impact:Improvement: −0.10 ±0.12 logMAR (T‑ionto, P=0.003) vs −0.03 ±0.06 logMAR (standard, P=0.10)
Trust score:4/5

In keratoconus patients, both conventional and accelerated corneal collagen cross-linking using methylcellulose-riboflavin improved visual acuity and maximum keratometry at 2 years with no difference between protocols.

Trust comment: Prospective randomized clinical trial with 2-year follow-up and objective ophthalmologic endpoints, but moderate sample size.

Study Details

PMID:30365412
Participants:40
Impact:statistically significant improvement vs baseline in both groups at 2 years
Trust score:4/5

Two CXL methods in progressive keratoconus were compared over 24 months; both stabilized disease but standard (epi-off) CXL produced greater corneal flattening and deeper stromal effects.

Trust comment: Randomized controlled trial with 2-year follow-up and objective measures; sample size moderate and methods clearly reported.

Study Details

PMID:27040458
Participants:119
Impact:Improved in both groups; transepithelial showed greater early improvement (p=0.044) but no difference at 24 months
Trust score:4/5

Corneal collagen crosslinking reduced keratoconus progression and improved visual acuity at 1 year, with corneal haze as the most common adverse finding.

Trust comment: Prospective, randomized multicenter controlled trial (n=205) with clear primary and secondary outcomes, high-quality evidence.

Study Details

PMID:28495149
Participants:205
Impact:improved on average (reported as 5.7 logMAR units improvement)
Trust score:5/5

Prospective randomized study comparing CXL protocols in 138 keratoconus patients found significant improvements in visual and refractive outcomes for several accelerated and conventional protocols at 12 months, with some protocols performing better than others.

Trust comment: Prospective randomized interventional study with 138 patients and 12-month follow-up; results reported with statistical significance though specific effect sizes are not provided in the abstract.

Study Details

PMID:26008626
Participants:138
Impact:Improved (statistically significant) in Groups I-II-III; not significant in Group IV
Trust score:4/5

In 179 subjects with post-refractive corneal ectasia, corneal collagen crosslinking (CXL) reduced progression and improved vision at 1 year versus sham.

Trust comment: Prospective, randomized, multicenter controlled trial with substantial sample size and clear clinically meaningful endpoints.

Study Details

PMID:28655538
Participants:179
Impact:mean improvement ≈ +5 logMAR letters
Trust score:5/5

After corneal collagen crosslinking, transient central corneal haze peaked at 1 month and returned to baseline by 6 months.

Trust comment: Prospective randomized controlled design with objective densitometry measures but small sample size.

Study Details

PMID:27492105
Participants:36
Impact:no significant relationship with densitometry (P = .30)
Trust score:4/5

Clinical trial of corneal collagen cross-linking showing greater corneal flattening and vision improvement when the ectatic cone was centrally located.

Trust comment: Prospective randomized controlled clinical trial with 99 eyes/76 patients and quantitative outcomes; good quality for clinical intervention.

Study Details

PMID:22692521
Participants:76
Impact:improved overall ≈ -0.10±0.18 logMAR
Trust score:4/5

Urinary CTX-II

1 evidences

In knee OA patients, IA-HA increased urinary CTX-II while NSAID decreased it; both improved symptoms.

Trust comment: Multicenter randomized controlled study with objective biomarker measurements and n=200, though this is a predefined sub-analysis.

Study Details

PMID:35331859
Participants:200
Impact:IA-HA +11.6% (337.7 → 370.7 ng/μmol Cr); NSAID -9.0% (423.2 → 370.3 ng/μmol Cr)
Trust score:4/5

Disease Activity Score (DAS)

1 evidences

Oral Gly‑X‑Y repeat sequences did not show clinically significant benefit versus placebo in active RA.

Trust comment: Randomized, placebo-controlled, double-blind crossover trial with reasonable design but potential confounders noted by authors.

Study Details

PMID:10220832
Participants:36
Impact:some within-subject improvement observed but no clinically significant benefit versus placebo by stringent EU criteria
Trust score:4/5

Joint swelling score

1 evidences

Oral Gly‑X‑Y repeat sequences did not show clinically significant benefit versus placebo in active RA.

Trust comment: Randomized, placebo-controlled, double-blind crossover trial with reasonable design but potential confounders noted by authors.

Study Details

PMID:10220832
Participants:36
Impact:improved during active treatment in many patients, but overall not significant against placebo
Trust score:4/5

bone alkaline phosphatase

1 evidences

Daily high-calcium mineral water (596 mg Ca) for 6 months lowered PTH and multiple bone turnover markers; adding 400 IU vitamin D provided no additional reduction.

Trust comment: Randomized double-blind placebo-controlled trial with large completed sample and objective biochemical endpoints.

Study Details

PMID:15744450
Participants:152
Impact:-11.5% (HCaMW vs placebo)
Trust score:4/5

C-terminal telopeptide of type I collagen (CTX)

1 evidences

Randomized double-blind trial in postmenopausal women showed risedronate (daily or once-weekly) strongly reduced bone formation and resorption markers over 6 months.

Trust comment: Randomized, double-blind active-controlled trial (n=102) with clear percent changes reported for key bone markers.

Study Details

PMID:20180356
Participants:102
Impact:−47.6% at 3 months; −62.9% at 6 months
Trust score:4/5

collagen density

1 evidences

A 12-week within-subject controlled clinical trial (one eye treated, the other as control) found the eye cream containing RFF, N-acetylneuraminic acid and peptides increased periorbital hydration, collagen density and skin elasticity with high participant satisfaction and no adverse effects.

Trust comment: Randomized, within-subject controlled 12-week trial with objective measures (n=37); small sample and product provided by company limit generalizability.

Study Details

PMID:38932444
Participants:37
Impact:+55.0% (treated vs control, 12 weeks)
Trust score:3/5

dermal thickness

1 evidences

In this randomized, double-blind trial, MAL plus red light increased dermal thickness and showed trends toward improved collagen and elastic tissue histology in photodamaged facial skin, though between-group differences were often non-significant, possibly due to low power.

Trust comment: Double-blind randomized trial with histological endpoints but limited power (38 samples analyzed) leading to mostly non-significant between-group differences.

Study Details

PMID:22582911
Participants:38
Impact:Increased after MAL + red light from baseline (p<0.01); between-group difference not significant (p=0.99)
Trust score:4/5

N-telopeptide (NTX)

1 evidences

Five years of risedronate reduced bone turnover markers and increased lumbar spine BMD, with no pathologic biopsy findings.

Trust comment: Extension randomized/controlled data with paired biopsies and multiple objective bone markers; moderate sample for biopsy analyses.

Study Details

PMID:15478000
Participants:48
Impact:−47.5% from baseline (risedronate)
Trust score:4/5

total hip BMD

4 evidences

Randomized trial of neridronate vs control in thalassaemia-associated osteoporosis; both groups received calcium + 400 IU vitamin D daily; neridronate increased BMD and reduced bone turnover and back pain.

Trust comment: Randomized phase 2 trial with clear clinical endpoints and 118 participants; open-label design lowers blinding robustness but results are plausible and reported with statistics.

Study Details

PMID:22571408
Participants:118
Impact:increase (significant at 6 and 12 months)
Trust score:4/5

Long‑term extension of ibandronate treatment showing sustained increases in lumbar spine and hip BMD and persistent reductions in type I collagen turnover markers over 3 years.

Trust comment: Large long‑term extension with clinically meaningful BMD and biochemical outcomes; post‑hoc elements and extension design modestly limit causal strength.

Study Details

PMID:18180976
Participants:719
Impact:+4.1% (150 mg) and +3.4% (100 mg) vs baseline at 3 years
Trust score:4/5

Alendronate increased bone mineral density over 2.5 years; all subjects received calcium and vitamin D but the study did not test vitamin D effects.

Trust comment: Double-blind, placebo-controlled randomized clinical trial with clear outcome measures and adequate sample size.

Study Details

PMID:9738515
Participants:120
Impact:+4.0% (long-term increase with alendronate)
Trust score:4/5

Short randomized trial showing rosiglitazone reduces biochemical markers of bone formation (including a procollagen marker) and decreases hip BMD in postmenopausal women.

Trust comment: Randomized, double‑blind controlled trial with clear biochemical and BMD endpoints but small sample and short duration (14 weeks).

Study Details

PMID:17264176
Participants:50
Impact:−1.9% (rosiglitazone) vs −0.2% (placebo); between‑group difference 1.7% (P<0.01)
Trust score:4/5

urine N-telopeptide (bone resorption marker)

1 evidences

Once-weekly alendronate significantly increased bone mineral density and reduced bone turnover markers versus calcium alone over one year.

Trust comment: Randomized trial in 58 women with clear, clinically relevant BMD and biomarker outcomes, but modest sample size.

Study Details

PMID:16076919
Participants:58
Impact:-55.6% at 12 months
Trust score:4/5

epidermal thickness

1 evidences

In a small double‑blind RCT, multispectral LED treatment did not show overall superiority vs sham for grade‑2 sacral pressure ulcers; LED increased epidermal thickness and basement membrane measures but wound area changes were similar.

Trust comment: Double‑blind RCT with biopsies and objective measures but small sample, dropout, and baseline imbalances limit generalizability.

Study Details

PMID:39178286
Participants:27
Impact:LED increased epidermal thickness significantly (LED 495.6 μm vs Sham 195.4 μm; p<0.001)
Trust score:3/5

muscle soreness

1 evidences

Small double-blind randomized trial in males: short-term collagen peptide supplementation modestly improved jump recovery and tended to reduce muscle soreness but did not affect inflammation or bone turnover markers.

Trust comment: Randomized double-blind trial but small sample (n=24) limiting power; objective measures but several null outcomes.

Study Details

PMID:30783776
Participants:24
Impact:CP 90.4 mm vs CON 125.7 mm at 48 h (≈−28%; P=0.071, not statistically significant)
Trust score:3/5

durability of cosmetic correction

2 evidences

Bovine collagen injections provided temporary wrinkle correction but were less durable and required more volume than hyaluronic acid; side-effect profiles were similar.

Trust comment: Randomized, double-blind multicenter trial with 138 patients and blinded assessments supports moderate-high reliability for comparative effectiveness of bovine collagen as a filler.

Study Details

PMID:12786700
Participants:138
Impact:less durable than hyaluronic acid at 6 months (HA superior in ~56.9–62.0% vs collagen superior in ~8.0–9.5%)
Trust score:4/5

Randomized trial comparing bovine collagen (Zyplast) versus hyaluronic acid (Perlane) for nasolabial fold correction; Perlane maintained results longer and caused fewer local reactions.

Trust comment: Randomized, evaluator-blind multicenter RCT with 68 patients; moderate-to-high internal validity though cosmetic outcomes partially subjective.

Study Details

PMID:15622265
Participants:68
Impact:Zyplast superior in 10.3% of patients vs Perlane 50.0% at 6 months (difference −39.7 percentage points; p<0.0004)
Trust score:4/5

required injection volume

1 evidences

Randomized trial comparing bovine collagen (Zyplast) versus hyaluronic acid (Perlane) for nasolabial fold correction; Perlane maintained results longer and caused fewer local reactions.

Trust comment: Randomized, evaluator-blind multicenter RCT with 68 patients; moderate-to-high internal validity though cosmetic outcomes partially subjective.

Study Details

PMID:15622265
Participants:68
Impact:Zyplast required larger mean volume (2.1 ml) vs Perlane (1.2 ml) to reach optimal result
Trust score:4/5

local injection-site reactions

2 evidences

Bovine collagen injections provided temporary wrinkle correction but were less durable and required more volume than hyaluronic acid; side-effect profiles were similar.

Trust comment: Randomized, double-blind multicenter trial with 138 patients and blinded assessments supports moderate-high reliability for comparative effectiveness of bovine collagen as a filler.

Study Details

PMID:12786700
Participants:138
Impact:no meaningful difference vs hyaluronic acid
Trust score:4/5

Randomized trial comparing bovine collagen (Zyplast) versus hyaluronic acid (Perlane) for nasolabial fold correction; Perlane maintained results longer and caused fewer local reactions.

Trust comment: Randomized, evaluator-blind multicenter RCT with 68 patients; moderate-to-high internal validity though cosmetic outcomes partially subjective.

Study Details

PMID:15622265
Participants:68
Impact:Higher frequency with Zyplast versus Perlane (less frequent with Perlane)
Trust score:4/5

collagen fibers

1 evidences

Intense pulsed light significantly improved clinical photoaging scores and increased collagen fibers on the treated side versus untreated control side.

Trust comment: Randomized split-face design with clinical, objective instrument measures and histology showing significant changes; sample size modest but methods robust.

Study Details

PMID:20166160
Participants:24
Impact:+increase (histologic, p<0.05)
Trust score:4/5

central corneal thickness (CCT)

2 evidences

Collagen cross-linking reduced corneal thickness short-term but provided no sustained improvement in pain, clarity, or vision and had higher rates of recurrent epithelial defects.

Trust comment: Randomized controlled human study with 12-month follow-up; moderate sample size but clear outcome measures and reported harms.

Study Details

PMID:33017120
Participants:42
Impact:-37.6 μm at 2 weeks and -63.8 μm at 4 weeks with CXL vs control; no difference at ≥12 weeks
Trust score:4/5

Randomized clinical trial in 23 patients with bullous keratopathy comparing accelerated corneal collagen crosslinking (CXL) versus hypertonic saline drops; CXL produced transient thinning of corneal thickness and transiently reduced irritation.

Trust comment: Prospective randomized trial but small (n=23), unblinded clinicians, and heterogeneous etiologies limit generalizability.

Study Details

PMID:31860972
Participants:23
Impact:CCT significantly thinner in CXL vs HS at 1 and 6 months (p=0.015 and p=0.044)
Trust score:3/5

irritation (subjective)

1 evidences

Randomized clinical trial in 23 patients with bullous keratopathy comparing accelerated corneal collagen crosslinking (CXL) versus hypertonic saline drops; CXL produced transient thinning of corneal thickness and transiently reduced irritation.

Trust comment: Prospective randomized trial but small (n=23), unblinded clinicians, and heterogeneous etiologies limit generalizability.

Study Details

PMID:31860972
Participants:23
Impact:Irritation score lower in CXL vs HS at 1 month (1.1 vs 1.6; p=0.012) but effect not maintained at 3 and 6 months
Trust score:3/5

best-corrected visual acuity (BCVA)

1 evidences

Randomized clinical trial in 23 patients with bullous keratopathy comparing accelerated corneal collagen crosslinking (CXL) versus hypertonic saline drops; CXL produced transient thinning of corneal thickness and transiently reduced irritation.

Trust comment: Prospective randomized trial but small (n=23), unblinded clinicians, and heterogeneous etiologies limit generalizability.

Study Details

PMID:31860972
Participants:23
Impact:No significant change from baseline in either group during follow-up
Trust score:3/5

ICTP (type I collagen degradation product)

1 evidences

Randomized study in chronic periodontitis patients: scaling/root planing plus local minocycline microspheres produced short-term reductions in a collagen degradation product (ICTP) and IL-1 in gingival crevicular fluid.

Trust comment: Randomized clinical study with 48 patients and biochemical endpoints; results demonstrate short-term biomarker changes though long-term effects unclear.

Study Details

PMID:12211491
Participants:48
Impact:Significant reduction at 1 month in SRP + minocycline group (p<0.05)
Trust score:4/5

IL-1 (GCF)

1 evidences

Randomized study in chronic periodontitis patients: scaling/root planing plus local minocycline microspheres produced short-term reductions in a collagen degradation product (ICTP) and IL-1 in gingival crevicular fluid.

Trust comment: Randomized clinical study with 48 patients and biochemical endpoints; results demonstrate short-term biomarker changes though long-term effects unclear.

Study Details

PMID:12211491
Participants:48
Impact:Significant reduction at 1 month in SRP + minocycline (p<0.05) and lower versus control at 1 month (p<0.02)
Trust score:4/5

bone defect area (radiographic)

1 evidences

Clinical comparison of antibiotic-containing bovine collagen composite (Targobone) versus autologous bone grafts for mandibular defects; both reduced defect area over 24 weeks, autograft achieved greater final closure.

Trust comment: Small comparative clinical series (n=21) showing radiographic defect reduction; non-randomized design and small sample reduce certainty.

Study Details

PMID:17415766
Participants:21
Impact:Targobone defect area decreased to 78% at 4 weeks and 21% at 24 weeks of baseline; autograft decreased to 69% at 4 weeks and 4.7% at 24 weeks
Trust score:3/5

hydroxyproline (collagen deposition)

1 evidences

Randomized trial in 64 nursing-home residents: supplemental oral fluids increased intake but did not increase hydroxyproline (collagen deposition), total body water, or subcutaneous oxygen over 5 days.

Trust comment: Randomized clinical trial with adequate sample for short-term physiology endpoints; negative results consistent and measurements objective.

Study Details

PMID:19821962
Participants:64
Impact:No significant increase during supplemental fluid treatment
Trust score:4/5

estimated total body water

1 evidences

Randomized trial in 64 nursing-home residents: supplemental oral fluids increased intake but did not increase hydroxyproline (collagen deposition), total body water, or subcutaneous oxygen over 5 days.

Trust comment: Randomized clinical trial with adequate sample for short-term physiology endpoints; negative results consistent and measurements objective.

Study Details

PMID:19821962
Participants:64
Impact:No significant increase during supplemental fluid treatment
Trust score:4/5

subcutaneous tissue oxygenation

1 evidences

Randomized trial in 64 nursing-home residents: supplemental oral fluids increased intake but did not increase hydroxyproline (collagen deposition), total body water, or subcutaneous oxygen over 5 days.

Trust comment: Randomized clinical trial with adequate sample for short-term physiology endpoints; negative results consistent and measurements objective.

Study Details

PMID:19821962
Participants:64
Impact:No significant increase during supplemental fluid treatment
Trust score:4/5

osseous bridging (fusion rate)

1 evidences

Multicenter randomized trial comparing rhPDGF-BB combined with beta-tricalcium phosphate–collagen matrix (a calcium phosphate graft substitute) versus autograft for ankle/hindfoot fusion; demonstrated noninferiority.

Trust comment: Multicenter randomized controlled trial with propensity-score pooled analysis (Level I), robust design and clinically relevant endpoints.

Study Details

PMID:31170812
Participants:104
Impact:68.1% vs 68.4% (−0.3 percentage points vs autograft)
Trust score:5/5

clinical healing status

1 evidences

Multicenter randomized trial comparing rhPDGF-BB combined with beta-tricalcium phosphate–collagen matrix (a calcium phosphate graft substitute) versus autograft for ankle/hindfoot fusion; demonstrated noninferiority.

Trust comment: Multicenter randomized controlled trial with propensity-score pooled analysis (Level I), robust design and clinically relevant endpoints.

Study Details

PMID:31170812
Participants:104
Impact:84.8% vs 90.7% (−5.9 percentage points vs autograft)
Trust score:5/5

pain

3 evidences

Multicenter randomized trial comparing rhPDGF-BB combined with beta-tricalcium phosphate–collagen matrix (a calcium phosphate graft substitute) versus autograft for ankle/hindfoot fusion; demonstrated noninferiority.

Trust comment: Multicenter randomized controlled trial with propensity-score pooled analysis (Level I), robust design and clinically relevant endpoints.

Study Details

PMID:31170812
Participants:104
Impact:reduced (less pain and morbidity vs autograft)
Trust score:5/5

Atelocollagen injections for partial supraspinatus tears provided greater and more sustained pain relief and better MRI-documented structural improvement than prolotherapy at 3 months.

Trust comment: Prospective randomized trial with MRI-confirmed structural outcomes but small sample (34 enrolled, 28 completers) and short follow-up (3 months).

Study Details

PMID:40773637
Participants:28
Impact:significant reduction with atelocollagen at 1 and 3 months (P=0.04; P<0.01)
Trust score:4/5

Randomized trial of trapeziectomy with or without porcine collagen (Permacol) implant; collagen group had frequent adverse reactions and worse clinical outcomes.

Trust comment: Randomized comparative design but small (n=26) and stopped early due to adverse events, limiting precision and generalizability.

Study Details

PMID:11281672
Participants:26
Impact:greater in collagen group (worse patient-reported pain)
Trust score:3/5

bone mineral density (lumbar and hip BMD)

1 evidences

Urinary NTx tracked antiresorptive effects of HRT and predicted subsequent changes in lumbar and hip BMD in recently postmenopausal women.

Trust comment: Randomized controlled 2-year study with 227 completers and clinically meaningful biomarker and BMD endpoints.

Study Details

PMID:9209198
Participants:227
Impact:BMD change correlated with baseline and change in NTx
Trust score:5/5

KOA pain intensity (target knee VAS)

1 evidences

Daily enzymatic hydrolysed collagen (Colatech®) improved knee OA pain and function and was superior to glucosamine over 13 weeks.

Trust comment: Randomized, double-blind multicenter trial (n=100) with clinically relevant endpoints but modest sample size and short duration.

Study Details

PMID:20401752
Participants:100
Impact:significant reduction with EHC vs baseline (p<0.05) and superior to GS
Trust score:4/5

WOMAC total score (clinical responders)

1 evidences

Daily enzymatic hydrolysed collagen (Colatech®) improved knee OA pain and function and was superior to glucosamine over 13 weeks.

Trust comment: Randomized, double-blind multicenter trial (n=100) with clinically relevant endpoints but modest sample size and short duration.

Study Details

PMID:20401752
Participants:100
Impact:34.04% responders (≤15-point decrease) with EHC vs 13.04% with GS
Trust score:4/5

patient global assessment (improvement)

1 evidences

Daily enzymatic hydrolysed collagen (Colatech®) improved knee OA pain and function and was superior to glucosamine over 13 weeks.

Trust comment: Randomized, double-blind multicenter trial (n=100) with clinically relevant endpoints but modest sample size and short duration.

Study Details

PMID:20401752
Participants:100
Impact:80.8% improved with EHC vs 46.6% with GS
Trust score:4/5

vertical bone gain

2 evidences

Both membrane strategies supported bone augmentation; nonresorbable membranes produced higher bone density and thinner pseudo‑periosteum than titanium-mesh plus cross-linked collagen membrane.

Trust comment: Randomized clinical study with small sample (36 analyzed) and objective histologic and radiographic measures; limited size reduces precision.

Study Details

PMID:31226196
Participants:36
Impact:4.2 ± 1.0 mm (d-PTFE) vs 4.1 ± 1.0 mm (Ti-mesh + collagen)
Trust score:4/5

Small randomized trial comparing resorbable collagen barriers supported by plates versus titanium-reinforced nonresorbable barriers for vertical ridge augmentation; both achieved bone gain but complications occurred in both groups.

Trust comment: Blinded randomized trial but small sample (22 patients) and preliminary report limit generalizability.

Study Details

PMID:17622003
Participants:22
Impact:Mean gain 2.2 mm (SD 1.5); no significant difference between groups (P≈0.99)
Trust score:3/5

bone density

1 evidences

Both membrane strategies supported bone augmentation; nonresorbable membranes produced higher bone density and thinner pseudo‑periosteum than titanium-mesh plus cross-linked collagen membrane.

Trust comment: Randomized clinical study with small sample (36 analyzed) and objective histologic and radiographic measures; limited size reduces precision.

Study Details

PMID:31226196
Participants:36
Impact:higher in d-PTFE group (P = .01)
Trust score:4/5

pseudo-periosteum thickness/type

1 evidences

Both membrane strategies supported bone augmentation; nonresorbable membranes produced higher bone density and thinner pseudo‑periosteum than titanium-mesh plus cross-linked collagen membrane.

Trust comment: Randomized clinical study with small sample (36 analyzed) and objective histologic and radiographic measures; limited size reduces precision.

Study Details

PMID:31226196
Participants:36
Impact:more type 1 (thinner) pseudo-periosteum with d-PTFE vs Ti-mesh + collagen (P = .01)
Trust score:4/5

collagen structural arrangement

1 evidences

Tendon samples from torn and uninjured rotator cuffs were compared by FTIR and torn tendons showed altered collagen structure and other chemical changes.

Trust comment: Good sample size and robust FTIR analysis on human tendon tissue but observational and not an intervention on health outcomes.

Study Details

PMID:21357960
Participants:92
Impact:altered in torn vs control tendons (distinct FTIR signatures)
Trust score:3/5

carbohydrates/phospholipids spectral changes

1 evidences

Tendon samples from torn and uninjured rotator cuffs were compared by FTIR and torn tendons showed altered collagen structure and other chemical changes.

Trust comment: Good sample size and robust FTIR analysis on human tendon tissue but observational and not an intervention on health outcomes.

Study Details

PMID:21357960
Participants:92
Impact:altered spectra (1030–1200 cm^-1) in torn tendons
Trust score:3/5

lipid spectral changes

1 evidences

Tendon samples from torn and uninjured rotator cuffs were compared by FTIR and torn tendons showed altered collagen structure and other chemical changes.

Trust comment: Good sample size and robust FTIR analysis on human tendon tissue but observational and not an intervention on health outcomes.

Study Details

PMID:21357960
Participants:92
Impact:altered spectra (2800–3000 cm^-1) in torn tendons
Trust score:3/5

distal probing depth

1 evidences

After extraction, placing a resorbable collagen membrane improved periodontal healing distal to the second molar at 6 months compared with suture alone.

Trust comment: Randomized controlled trial with clinically relevant endpoints and reasonable sample though modest size and some loss to follow-up.

Study Details

PMID:25959878
Participants:56
Impact:greater improvement at 6 months in RM group (P < .05)
Trust score:4/5

distal vestibular attachment level

1 evidences

After extraction, placing a resorbable collagen membrane improved periodontal healing distal to the second molar at 6 months compared with suture alone.

Trust comment: Randomized controlled trial with clinically relevant endpoints and reasonable sample though modest size and some loss to follow-up.

Study Details

PMID:25959878
Participants:56
Impact:greater improvement at 6 months in RM group (P < .05)
Trust score:4/5

bone fill distal to L2M

1 evidences

After extraction, placing a resorbable collagen membrane improved periodontal healing distal to the second molar at 6 months compared with suture alone.

Trust comment: Randomized controlled trial with clinically relevant endpoints and reasonable sample though modest size and some loss to follow-up.

Study Details

PMID:25959878
Participants:56
Impact:greater improvement at 6 months in RM group (P < .05)
Trust score:4/5

type II collagen breakdown (CTX-II)

1 evidences

Single IV zoledronate transiently reduced urinary markers of type II collagen breakdown and markedly suppressed type I collagen resorption markers in Paget's disease patients.

Trust comment: Double-blind randomized trial with valid biochemical endpoints but small sample size and short follow-up for cartilage effects.

Study Details

PMID:11344044
Participants:26
Impact:median decrease ~25% at day 5 vs placebo, returned to baseline by day 10
Trust score:4/5

type I collagen resorption (alpha CTX-I)

1 evidences

Single IV zoledronate transiently reduced urinary markers of type II collagen breakdown and markedly suppressed type I collagen resorption markers in Paget's disease patients.

Trust comment: Double-blind randomized trial with valid biochemical endpoints but small sample size and short follow-up for cartilage effects.

Study Details

PMID:11344044
Participants:26
Impact:decrease maximal ~51% at day 10 and remained suppressed through 60 days
Trust score:4/5

serum NTx level

1 evidences

Serum NTx shows diurnal variation and is reduced by alendronate (~25% lower over 24 h), demonstrating responsiveness of this collagen-derived bone resorption marker to therapy.

Trust comment: Well-controlled measurement study in humans with clear numeric effects on a validated biochemical marker, though sample for 24-h profiling was modest.

Study Details

PMID:9685512
Participants:38
Impact:~25% lower over 24 h with alendronate vs placebo (mean daytime and nighttime values lower)
Trust score:4/5

diurnal pattern of serum NTx

1 evidences

Serum NTx shows diurnal variation and is reduced by alendronate (~25% lower over 24 h), demonstrating responsiveness of this collagen-derived bone resorption marker to therapy.

Trust comment: Well-controlled measurement study in humans with clear numeric effects on a validated biochemical marker, though sample for 24-h profiling was modest.

Study Details

PMID:9685512
Participants:38
Impact:significant diurnal variation maintained with alendronate (peak ~05:04, nadir ~13:20)
Trust score:4/5

urinary NTX (bone resorption)

3 evidences

In elderly osteoporotic women, alendronate increased lumbar BMD and reduced bone resorption more than etidronate; both treatments reduced back pain.

Trust comment: Open-label head-to-head prospective study with small sample but clear biochemical and BMD differences.

Study Details

PMID:16385649
Participants:50
Impact:alendronate −47.0% (6 mo) and −49.9% (12 mo) vs etidronate −13.2% (6 mo) and −38.8% (12 mo)
Trust score:3/5

Ospemifene dose-dependently reduced bone resorption and formation markers (collagen-related biochemical markers) over 3 months in postmenopausal women.

Trust comment: Randomized double-blind study with adequate sample and clear, dose-dependent biochemical effects on collagen-related markers.

Study Details

PMID:15255284
Participants:159
Impact:decreases of 6.1%, 9.4%, and 12.9% at 30, 60, and 90 mg respectively (vs placebo)
Trust score:4/5

In postmenopausal breast cancer patients, tamoxifen reduced markers of bone resorption and formation and increased spine and femoral BMD, whereas toremifene showed smaller effects.

Trust comment: Randomized comparison with biochemical and BMD endpoints in 30 patients; moderate size but measured biomarkers and BMD are standard outcomes.

Study Details

PMID:9543133
Participants:30
Impact:decrease at 6 months: tamoxifen -33%; toremifene -16%
Trust score:4/5

PINP (bone formation, type I procollagen)

1 evidences

Ospemifene dose-dependently reduced bone resorption and formation markers (collagen-related biochemical markers) over 3 months in postmenopausal women.

Trust comment: Randomized double-blind study with adequate sample and clear, dose-dependent biochemical effects on collagen-related markers.

Study Details

PMID:15255284
Participants:159
Impact:decreases of 9.8% (60 mg) and 15.3% (90 mg)
Trust score:4/5

PICP (type I procollagen)

1 evidences

Ospemifene dose-dependently reduced bone resorption and formation markers (collagen-related biochemical markers) over 3 months in postmenopausal women.

Trust comment: Randomized double-blind study with adequate sample and clear, dose-dependent biochemical effects on collagen-related markers.

Study Details

PMID:15255284
Participants:159
Impact:decreases of 12.0% (60 mg) and 11.9% (90 mg); CTX decreased 4.8% at 90 mg; bone ALP decreased 1.9% and 2.6% at 60 and 90 mg
Trust score:4/5

maximum keratometry (Kmax)

8 evidences

Corneal collagen crosslinking effectively reduced progression of keratoconus over 5 years, with treated eyes showing decreased keratometry compared to progression in control eyes.

Trust comment: Prospective randomized contralateral-eye controlled trial with objective outcomes and 5-year follow-up.

Study Details

PMID:34117699
Participants:38
Impact:treated -1.45 ± 2.25 D vs control +1.71 ± 2.46 D at 5 years (p<0.001)
Trust score:5/5

Two corneal cross-linking procedures stabilized keratoconus over 12 months with modest differences; iontophoresis transepithelial treatment gave significant visual gains but slightly less corneal flattening than standard protocol.

Trust comment: Prospective randomized controlled trial with 12‑month follow-up but modest sample size (34 eyes, 25 patients).

Study Details

PMID:28283279
Participants:25
Impact:Flattening at 12 months: −0.52 ±1.30 D (T‑ionto, P=0.06) vs −0.82 ±1.20 D (standard, P=0.04)
Trust score:4/5

Epithelium‑off corneal collagen cross‑linking halted keratoconus progression and reduced maximum K, while transepithelial treatment was less effective and many patients progressed.

Trust comment: Prospective randomized controlled trial with 3‑year follow‑up showing clear, statistically significant differences in primary outcomes.

Study Details

PMID:26266436
Participants:70
Impact:epithelium‑off: −2.4 D; transepithelial: +1.1 D
Trust score:5/5

Transepithelial (epi-on) CXL in keratoconus produced a small but statistically significant flattening of maximum K (−0.9 D) and improved CDVA at 6 months in this small cohort.

Trust comment: Prospective clinical trial with small sample and short (6-month) follow-up; results suggest short-term benefit but limited durability data.

Study Details

PMID:25465683
Participants:25
Impact:-0.9 D mean flattening (58.7 D to 57.8 D) at 6 months (P=0.01)
Trust score:3/5

In pediatric keratoconus, both conventional and accelerated CXL improved vision and reduced corneal steepness with no progression over 3 years; differences were most evident at 1 year.

Trust comment: Prospective randomized contralateral-eye design in pediatric patients with 3-year follow-up; moderate sample size but robust within-patient comparison.

Study Details

PMID:29564806
Participants:34
Impact:Kmax reduced in both groups with a significant between-group difference at 12 months (improvement maintained through 3 years)
Trust score:4/5

Corneal collagen crosslinking reduced keratoconus progression and improved visual acuity at 1 year, with corneal haze as the most common adverse finding.

Trust comment: Prospective, randomized multicenter controlled trial (n=205) with clear primary and secondary outcomes, high-quality evidence.

Study Details

PMID:28495149
Participants:205
Impact:decreased by 1.6 D from baseline to 1 year in treatment group; 31.5% had ≥2.0 D decrease, 5.6% had ≥2.0 D increase
Trust score:5/5

Corneal collagen cross-linking improved vision and reduced corneal curvature at 6 months versus sham, with expected cellular changes on confocal microscopy.

Trust comment: Prospective randomized sham-controlled trial with objective measures and 6-month follow-up; moderate sample size (43 eyes).

Study Details

PMID:25708282
Participants:43
Impact:decreased by mean 1.2 ± 0.8 D (P = 0.01)
Trust score:4/5

Prospective study showing modest flattening of maximum keratometry and regularization of epithelial thickness profile 6 months after epithelium-off CXL.

Trust comment: Prospective single-center study with adequate sample size (n=93); direct clinical measurements but focused on surgical cross-linking effects rather than collagen supplementation.

Study Details

PMID:29889294
Participants:93
Impact:mean flattened from 58.90 to 57.80 D at 6 months (≈ -1.10 D)
Trust score:3/5

endothelial cell density (ECD)

1 evidences

In keratoconus patients, both conventional and accelerated corneal collagen cross-linking using methylcellulose-riboflavin improved visual acuity and maximum keratometry at 2 years with no difference between protocols.

Trust comment: Prospective randomized clinical trial with 2-year follow-up and objective ophthalmologic endpoints, but moderate sample size.

Study Details

PMID:30365412
Participants:40
Impact:no significant change in either group at 2 years
Trust score:4/5

intraocular pressure (IOP) reduction

3 evidences

Adding a biodegradable collagen implant (Ologen) to MMC did not improve IOP lowering compared with MMC alone over 12 months.

Trust comment: Prospective randomized comparative study (50 patients) with clear outcomes and 12-month follow-up; moderate-high quality.

Study Details

PMID:32677614
Participants:50
Impact:-55.0% (MMC) vs -44.2% (MMC+Ologen) at 12 months; postoperative IOP 11.33 mmHg vs 14.35 mmHg (p<0.001 between visits)
Trust score:4/5

Randomized trial comparing atelocollagen implant vs mitomycin C during trabeculectomy; the collagen implant group had less pressure reduction and lower surgical success than MMC.

Trust comment: Prospective randomized trial in humans but small sample and single-center limits generalizability.

Study Details

PMID:24401481
Participants:30
Impact:Mean IOP at 12 months 15.9 ±4.5 mmHg (OLO, 43% reduction) vs 11.0 ±2.6 mmHg (MMC, 54% reduction)
Trust score:3/5

A porcine collagen implant (Ologen) used during trabeculectomy lowered intraocular pressure similarly to mitomycin‑C over 5 years with comparable safety.

Trust comment: Randomized, masked trial with 5-year follow-up but small sample (n=40) limits power for secondary endpoints.

Study Details

PMID:26946419
Participants:40
Impact:-42.1% (Ologen group endpoint vs baseline); no significant difference vs MMC (40.9%; P=0.827)
Trust score:4/5

surgical success rate (IOP ≤15 mmHg)

1 evidences

Adding a biodegradable collagen implant (Ologen) to MMC did not improve IOP lowering compared with MMC alone over 12 months.

Trust comment: Prospective randomized comparative study (50 patients) with clear outcomes and 12-month follow-up; moderate-high quality.

Study Details

PMID:32677614
Participants:50
Impact:86.3% (MMC) vs 73.9% (MMC+Ologen); difference not significant (p=0.46)
Trust score:4/5

secondary clinical outcomes

1 evidences

Oral chicken type II collagen (0.25 mg/day) showed no statistically significant benefit over placebo in active rheumatoid arthritis over 6 months.

Trust comment: Double-blind RCT but small sample (60) and no significant primary outcome; moderate-risk of type II error.

Study Details

PMID:11072596
Participants:60
Impact:no significant improvement vs placebo on ITT analysis over 6 months
Trust score:3/5

clinical remission (subset)

1 evidences

Oral chicken type II collagen (0.25 mg/day) showed no statistically significant benefit over placebo in active rheumatoid arthritis over 6 months.

Trust comment: Double-blind RCT but small sample (60) and no significant primary outcome; moderate-risk of type II error.

Study Details

PMID:11072596
Participants:60
Impact:2 collagen-treated patients achieved remission (anecdotal)
Trust score:3/5

swelling (objective)

1 evidences

Secondary closure had less swelling and better early mouth opening; membrane-based primary closure was similar to primary closure for immediate discomfort but showed minimal dehiscence and no alveolitis.

Trust comment: Prospective randomized trial with 90 patients, blinded outcome assessment and objective measures; good quality for surgical question.

Study Details

PMID:28982352
Participants:90
Impact:Day 2: SC 9.15 mm vs PC 14.82 mm vs MBPC 18.43 mm; Day 7: SC 2.72 mm vs PC 5.96 mm vs MBPC 8.17 mm (SC significantly lower)
Trust score:4/5

mouth opening (percent)

1 evidences

Secondary closure had less swelling and better early mouth opening; membrane-based primary closure was similar to primary closure for immediate discomfort but showed minimal dehiscence and no alveolitis.

Trust comment: Prospective randomized trial with 90 patients, blinded outcome assessment and objective measures; good quality for surgical question.

Study Details

PMID:28982352
Participants:90
Impact:Day 2: SC 68.76% vs PC 60.38% vs MBPC 59.76% (SC significantly better); Day 7 differences NS
Trust score:4/5

wound dehiscence / alveolitis

1 evidences

Secondary closure had less swelling and better early mouth opening; membrane-based primary closure was similar to primary closure for immediate discomfort but showed minimal dehiscence and no alveolitis.

Trust comment: Prospective randomized trial with 90 patients, blinded outcome assessment and objective measures; good quality for surgical question.

Study Details

PMID:28982352
Participants:90
Impact:MBPC dehiscence 6.7% vs PC 20%; MBPC had no alveolitis (clinically minimal complications)
Trust score:4/5

corneal resistance factor (CRF)

1 evidences

Randomized clinical trial measuring corneal biomechanics up to 1 year after corneal collagen cross-linking (CXL); no meaningful change in measured biomechanical indices at 1 year.

Trust comment: Prospective randomized controlled clinical trial with objective biomechanical measures but single-center and measured by ORA which may have limited sensitivity.

Study Details

PMID:21993470
Participants:69
Impact:≈+0.29 units (no significant change; P=0.10)
Trust score:4/5

type III procollagen aminoterminal propeptide

1 evidences

Thrombolytic therapy increased markers of collagen degradation (type III aminoterminal propeptide), with larger rises after streptokinase than tPA; type I propeptide showed transient early decrease then secondary rise.

Trust comment: Small randomized study (24 patients) with relevant biochemical markers; results plausible but limited by small size and older methods.

Study Details

PMID:8554022
Participants:24
Impact:max mean increases: streptokinase +44% vs tPA +16% during infusion (marker of collagen breakdown)
Trust score:3/5

type I procollagen carboxyterminal propeptide

1 evidences

Thrombolytic therapy increased markers of collagen degradation (type III aminoterminal propeptide), with larger rises after streptokinase than tPA; type I propeptide showed transient early decrease then secondary rise.

Trust comment: Small randomized study (24 patients) with relevant biochemical markers; results plausible but limited by small size and older methods.

Study Details

PMID:8554022
Participants:24
Impact:no overall change during therapy; transient decrease at day 2 followed by increase at days 4–6
Trust score:3/5

aminoterminal propeptide of type III procollagen

1 evidences

Patients post-anterior MI randomized to an aldosterone inhibitor had lower markers of collagen synthesis and less LV dilation over 12 months compared with placebo.

Trust comment: Randomized clinical trial with 12-month follow-up and biologic and clinical outcomes reported; moderate sample size but clear endpoints.

Study Details

PMID:11136485
Participants:46
Impact:Lower in aldosterone inhibitor group vs placebo at 3, 6, and 12 months (significant)
Trust score:4/5

left ventricular volume

1 evidences

Patients post-anterior MI randomized to an aldosterone inhibitor had lower markers of collagen synthesis and less LV dilation over 12 months compared with placebo.

Trust comment: Randomized clinical trial with 12-month follow-up and biologic and clinical outcomes reported; moderate sample size but clear endpoints.

Study Details

PMID:11136485
Participants:46
Impact:Smaller LV volumes in active treatment vs placebo at 6 and 12 months (significant)
Trust score:4/5

mean percent wound area reduction

1 evidences

Randomized trial (2:1) showed the collagen-alginate dressing reduced wound size more than saline gauze and had higher rates of marked reduction and complete healing over 8 weeks.

Trust comment: Randomized clinical trial with clinically relevant wound outcomes; moderate sample size though some unadjusted comparisons were non-significant while adjusted analysis favored collagen dressing.

Study Details

PMID:9729942
Participants:75
Impact:80.6% ±6% vs 61.1% ±26% (collagen-alginate vs gauze; p = 0.4692 reported for unadjusted means)
Trust score:4/5

patients achieving ≥75% wound area reduction

1 evidences

Randomized trial (2:1) showed the collagen-alginate dressing reduced wound size more than saline gauze and had higher rates of marked reduction and complete healing over 8 weeks.

Trust comment: Randomized clinical trial with clinically relevant wound outcomes; moderate sample size though some unadjusted comparisons were non-significant while adjusted analysis favored collagen dressing.

Study Details

PMID:9729942
Participants:75
Impact:78% vs 60% (collagen-alginate vs gauze)
Trust score:4/5

complete healing

1 evidences

Randomized trial (2:1) showed the collagen-alginate dressing reduced wound size more than saline gauze and had higher rates of marked reduction and complete healing over 8 weeks.

Trust comment: Randomized clinical trial with clinically relevant wound outcomes; moderate sample size though some unadjusted comparisons were non-significant while adjusted analysis favored collagen dressing.

Study Details

PMID:9729942
Participants:75
Impact:48% vs 36% (collagen-alginate vs gauze)
Trust score:4/5

mean hemostasis time

2 evidences

In randomized carotid endarterectomy, collagen-impregnated Dacron (Hemashield) patching was associated with higher perioperative stroke, thrombosis, and early restenosis rates compared with PTFE, but had shorter hemostasis time.

Trust comment: Large randomized perioperative trial (n=200 CEAs) with clear clinical endpoints though follow-up here is limited to early (30-day) outcomes.

Study Details

PMID:11802143
Participants:200
Impact:shorter for HP: 3.4 min vs PTFE 14.4 min
Trust score:4/5

Randomized trial comparing PTFE patch versus collagen-impregnated Dacron patch during carotid endarterectomy found similar early neurologic event rates but different hemostasis times.

Trust comment: Large randomized surgical trial directly comparing a collagen-impregnated patch to PTFE with objective perioperative outcomes, though some differences were not statistically significant.

Study Details

PMID:17466785
Participants:200
Impact:5.1 vs 3.7 minutes (ACUSEAL vs Hemashield-Finesse; P = .01)
Trust score:4/5

early ≥50% restenosis rate

1 evidences

Randomized trial comparing PTFE patch versus collagen-impregnated Dacron patch during carotid endarterectomy found similar early neurologic event rates but different hemostasis times.

Trust comment: Large randomized surgical trial directly comparing a collagen-impregnated patch to PTFE with objective perioperative outcomes, though some differences were not statistically significant.

Study Details

PMID:17466785
Participants:200
Impact:0% ACUSEAL vs 4% Hemashield-Finesse
Trust score:4/5

combined early morbidity (TIA, stroke, ≥50% restenosis, thrombosis)

1 evidences

Randomized trial comparing PTFE patch versus collagen-impregnated Dacron patch during carotid endarterectomy found similar early neurologic event rates but different hemostasis times.

Trust comment: Large randomized surgical trial directly comparing a collagen-impregnated patch to PTFE with objective perioperative outcomes, though some differences were not statistically significant.

Study Details

PMID:17466785
Participants:200
Impact:2% ACUSEAL vs 8% Hemashield-Finesse (P = .10)
Trust score:4/5

subepithelial collagen type III deposition

1 evidences

Six months of inhaled beclomethasone reduced subepithelial type III collagen deposition and MMP-9 while increasing TIMP-1 in bronchial biopsies from asthmatic subjects.

Trust comment: Double-blind randomized study with tissue-level endpoints and significant biomarker changes, though modest sample size (n=30).

Study Details

PMID:10452757
Participants:30
Impact:Decreased with inhaled BDP vs placebo (P < .01)
Trust score:4/5

submucosal MMP-9 expression

1 evidences

Six months of inhaled beclomethasone reduced subepithelial type III collagen deposition and MMP-9 while increasing TIMP-1 in bronchial biopsies from asthmatic subjects.

Trust comment: Double-blind randomized study with tissue-level endpoints and significant biomarker changes, though modest sample size (n=30).

Study Details

PMID:10452757
Participants:30
Impact:Decreased with inhaled BDP (P < .01)
Trust score:4/5

submucosal TIMP-1 expression

1 evidences

Six months of inhaled beclomethasone reduced subepithelial type III collagen deposition and MMP-9 while increasing TIMP-1 in bronchial biopsies from asthmatic subjects.

Trust comment: Double-blind randomized study with tissue-level endpoints and significant biomarker changes, though modest sample size (n=30).

Study Details

PMID:10452757
Participants:30
Impact:Increased with inhaled BDP (P < .05)
Trust score:4/5

fistula healing rate (collagen-fibrin glue)

1 evidences

Prospective human study testing two formats of cross-linked collagen implants for anal fistula repair; both were safe and collagen-fibrin glue had higher long-term healing than solid implant.

Trust comment: Prospective phase 1 randomized human study but small sample (n=29) and limited power, moderate quality.

Study Details

PMID:19863602
Participants:29
Impact:12/15 healed (80%) at 29 months
Trust score:3/5

fistula healing rate (solid collagen implant)

1 evidences

Prospective human study testing two formats of cross-linked collagen implants for anal fistula repair; both were safe and collagen-fibrin glue had higher long-term healing than solid implant.

Trust comment: Prospective phase 1 randomized human study but small sample (n=29) and limited power, moderate quality.

Study Details

PMID:19863602
Participants:29
Impact:7/13 healed (54%) at 29 months
Trust score:3/5

continence / sphincter function

1 evidences

Prospective human study testing two formats of cross-linked collagen implants for anal fistula repair; both were safe and collagen-fibrin glue had higher long-term healing than solid implant.

Trust comment: Prospective phase 1 randomized human study but small sample (n=29) and limited power, moderate quality.

Study Details

PMID:19863602
Participants:29
Impact:no disturbance at 3 months; sphincter function unchanged
Trust score:3/5

wrinkle correction durability (Zyplast collagen)

1 evidences

Multicenter randomized study comparing Juvéderm (HA) to Zyplast collagen for nasolabial fold correction; HA maintained correction longer while Zyplast collagen did not sustain clinically significant correction >9 months.

Trust comment: Large multicenter double-blind randomized trial (n=292) with robust clinical endpoints; collagen used as active comparator.

Study Details

PMID:19083502
Participants:292
Impact:did not maintain clinically significant correction at >9 months
Trust score:4/5

local treatment site reactions

1 evidences

Multicenter randomized study comparing Juvéderm (HA) to Zyplast collagen for nasolabial fold correction; HA maintained correction longer while Zyplast collagen did not sustain clinically significant correction >9 months.

Trust comment: Large multicenter double-blind randomized trial (n=292) with robust clinical endpoints; collagen used as active comparator.

Study Details

PMID:19083502
Participants:292
Impact:comparable to HA (no major safety differences)
Trust score:4/5

healing rate

4 evidences

A randomized trial showing Promogran dressing reduced wound surface area more than control and had a higher (but not statistically significant) healing proportion.

Trust comment: Randomized human trial with blinded assessments and intent-to-treat analysis but modest sample size and loss to follow-up.

Study Details

PMID:12430368
Participants:73
Impact:Promogran 41% healed vs Adaptic 31% healed (Δ +10 percentage points; p=0.373)
Trust score:4/5

Randomized trial comparing PRF membrane versus collagen membrane after oral mucosal excision; PRF showed less pain and faster healing at early time points.

Trust comment: Small RCT with clear outcomes but limited sample size and short follow-up for recurrence/complications.

Study Details

PMID:29601789
Participants:30
Impact:accelerated healing with PRF at 15 and 30 days (no difference at 60 days)
Trust score:3/5

A protease-modulating collagen-containing dressing led to more frequent and faster healing of neuropathic diabetic foot ulcers versus standard care over 6 weeks.

Trust comment: Randomized controlled trial with clear, significant outcomes but small sample and short follow-up.

Study Details

PMID:17580028
Participants:38
Impact:63% healed with collagen dressing vs 15% with control at 6 weeks (absolute +48%)
Trust score:4/5

ORC/collagen matrix applied to pressure sores accelerated healing and reduced protease (elastase and plasmin) activity in wound exudate versus foam dressing control.

Trust comment: Prospective randomized study in 33 patients showing clinical benefit and correlated biochemical changes; limited sample size but direct clinical relevance for collagen wound matrix.

Study Details

PMID:26011241
Participants:33
Impact:significantly faster healing with ORC/collagen matrix vs control
Trust score:4/5

wound surface area reduction

1 evidences

A randomized trial showing Promogran dressing reduced wound surface area more than control and had a higher (but not statistically significant) healing proportion.

Trust comment: Randomized human trial with blinded assessments and intent-to-treat analysis but modest sample size and loss to follow-up.

Study Details

PMID:12430368
Participants:73
Impact:Promogran mean −54.4% vs Adaptic −36.5% (Δ +17.9 pp; p<0.001)
Trust score:4/5

wrinkle severity (WSRS) change

1 evidences

Within-subject randomized injection study showing porcine and bovine atelocollagen similarly improved nasolabial wrinkle scores at 6 months with manageable local redness.

Trust comment: Randomized, within-subject design with adequate sample and objective scoring, though cosmetic outcomes are partly subjective.

Study Details

PMID:25272190
Participants:73
Impact:Porcine: 2.90→2.15 (Δ −0.75); Bovine: 2.85→2.21 (Δ −0.64); no significant difference
Trust score:4/5

injection-related local adverse effects

1 evidences

Within-subject randomized injection study showing porcine and bovine atelocollagen similarly improved nasolabial wrinkle scores at 6 months with manageable local redness.

Trust comment: Randomized, within-subject design with adequate sample and objective scoring, though cosmetic outcomes are partly subjective.

Study Details

PMID:25272190
Participants:73
Impact:Redness in 12/73 subjects
Trust score:4/5

clinical success (relief of epiphora)

1 evidences

Randomized study of Ologen (porcine atelocollagen matrix) in DCR surgery showing improved dye clearance and a numerically higher clinical success rate versus control.

Trust comment: Prospective randomized study with clear clinical endpoints and statistically significant dye clearance improvement, but limited sample size.

Study Details

PMID:30236087
Participants:60
Impact:Control 86.7% vs Ologen 96.7% (Δ +10 pp; p=0.353)
Trust score:4/5

dye clearance time

1 evidences

Randomized study of Ologen (porcine atelocollagen matrix) in DCR surgery showing improved dye clearance and a numerically higher clinical success rate versus control.

Trust comment: Prospective randomized study with clear clinical endpoints and statistically significant dye clearance improvement, but limited sample size.

Study Details

PMID:30236087
Participants:60
Impact:Control 4.5±0.6 min vs Ologen 3.9±0.4 min (difference −0.6 min; p=0.001)
Trust score:4/5

persistence of corrective response at 9 months

1 evidences

Randomized multicenter study showing porcine-derived ribose-cross-linked collagen filler maintained corrective effect in most subjects up to 9 months and in many up to 12 months.

Trust comment: Randomized, multicenter, reasonably large sample with clear outcome measures and safety reporting.

Study Details

PMID:18547179
Participants:149
Impact:95.3% of subjects met persistence criteria at 9 months
Trust score:4/5

persistence of corrective response at 12 months

1 evidences

Randomized multicenter study showing porcine-derived ribose-cross-linked collagen filler maintained corrective effect in most subjects up to 9 months and in many up to 12 months.

Trust comment: Randomized, multicenter, reasonably large sample with clear outcome measures and safety reporting.

Study Details

PMID:18547179
Participants:149
Impact:76.5% of subjects met persistence criteria at 12 months
Trust score:4/5

bone resorption marker (CTX)

2 evidences

Randomized double-blind trial in postmenopausal women showing daily 10 g collagen hydrolysate for 24 weeks did not alter biochemical markers of bone turnover versus placebo.

Trust comment: Randomized, double-blind human trial but modest sample size and biochemical (not clinical) endpoints; results show no effect.

Study Details

PMID:19892499
Participants:71
Impact:CH: 0.40→0.48 ng/mL; Placebo: 0.47→0.57 ng/mL (both increased; no difference between groups)
Trust score:4/5

In 74 postmenopausal women, bisphosphonate therapy (clodronate or yearly zoledronate) reduced bone turnover markers and produced differential effects on Wnt inhibitors (transient DKK1 increases with zoledronate; delayed SOST increase with clodronate).

Trust comment: Data from participants in multicenter randomized placebo-controlled trials with standard biochemical endpoints, supporting credibility.

Study Details

PMID:25003812
Participants:74
Impact:Significant decrease during bisphosphonate treatment versus baseline and placebo
Trust score:4/5

bone formation marker (osteocalcin)

1 evidences

Randomized double-blind trial in postmenopausal women showing daily 10 g collagen hydrolysate for 24 weeks did not alter biochemical markers of bone turnover versus placebo.

Trust comment: Randomized, double-blind human trial but modest sample size and biochemical (not clinical) endpoints; results show no effect.

Study Details

PMID:19892499
Participants:71
Impact:CH: 24.8→29.0 ng/mL; Placebo: 28.1→31.8 ng/mL (both increased; no difference between groups)
Trust score:4/5

complication rate

2 evidences

Randomized trial comparing two acellular dermal matrices used in immediate breast reconstruction; clinical outcomes, histology, satisfaction, and costs were similar between groups.

Trust comment: Small randomized clinical trial directly evaluating collagen-containing dermal matrices with objective outcomes but limited sample size.

Study Details

PMID:28341592
Participants:30
Impact:no significant difference between groups (p>0.05)
Trust score:3/5

Using a collagen plug after catheterization shortened bleeding time and caused less pain with similar complication rates.

Trust comment: Randomized study with objective measures and duplex follow-up; moderate sample size supports findings.

Study Details

PMID:9040266
Participants:62
Impact:no difference (P=0.82)
Trust score:4/5

vessel density (dermal vs implant side)

1 evidences

Randomized trial comparing two acellular dermal matrices used in immediate breast reconstruction; clinical outcomes, histology, satisfaction, and costs were similar between groups.

Trust comment: Small randomized clinical trial directly evaluating collagen-containing dermal matrices with objective outcomes but limited sample size.

Study Details

PMID:28341592
Participants:30
Impact:greater on dermal side vs implant side (no exact % given)
Trust score:3/5

patient satisfaction (BRECON-31)

1 evidences

Randomized trial comparing two acellular dermal matrices used in immediate breast reconstruction; clinical outcomes, histology, satisfaction, and costs were similar between groups.

Trust comment: Small randomized clinical trial directly evaluating collagen-containing dermal matrices with objective outcomes but limited sample size.

Study Details

PMID:28341592
Participants:30
Impact:no significant difference between groups
Trust score:3/5

facial bone wall thickness

1 evidences

Randomized comparative study showing similar peri-implant buccal bone stability at one year between autogenous bone+DBBM (with collagen membrane) and FDBA (with collagen membrane).

Trust comment: Randomized clinical study using collagen membranes in both arms; moderate sample size and direct clinical measurements but does not isolate collagen membrane effect.

Study Details

PMID:35506299
Participants:48
Impact:no significant difference between groups at 12 months (means ≈1.6–2.45 mm vs 1.6–2.10 mm)
Trust score:3/5

facial vertical bone wall peak (IP-FC)

1 evidences

Randomized comparative study showing similar peri-implant buccal bone stability at one year between autogenous bone+DBBM (with collagen membrane) and FDBA (with collagen membrane).

Trust comment: Randomized clinical study using collagen membranes in both arms; moderate sample size and direct clinical measurements but does not isolate collagen membrane effect.

Study Details

PMID:35506299
Participants:48
Impact:no significant difference (mean 0.8 mm control vs 0.5 mm test)
Trust score:3/5

implant clinical success at 12 months

1 evidences

Randomized comparative study showing similar peri-implant buccal bone stability at one year between autogenous bone+DBBM (with collagen membrane) and FDBA (with collagen membrane).

Trust comment: Randomized clinical study using collagen membranes in both arms; moderate sample size and direct clinical measurements but does not isolate collagen membrane effect.

Study Details

PMID:35506299
Participants:48
Impact:all 48 implants clinically successful (100%)
Trust score:3/5

Hydroxyproline (marker of collagen absorption)

1 evidences

Double-blind randomized placebo-controlled trial (25 men): daily 15 g collagen peptides during 12 weeks resistance training increased absorption marker, fat-free mass, and produced broader proteomic adaptations versus placebo.

Trust comment: Well-designed double-blind randomized placebo-controlled trial with objective biochemical and proteomic endpoints but small sample size.

Study Details

PMID:31091754
Participants:25
Impact:In COL group increased from 33.3±19.7 to 95.8±27.1 µmol/L 2 h post-ingestion (p≤0.0125)
Trust score:4/5

Fat-free mass (FFM)

3 evidences

Randomized, double-blind 24-week pilot trial in knee OA patients comparing HC-II (type II collagen hydrolysate), EC-HC-II (chicken essence + HC-II), glucosamine, and placebo; HC-II reduced early pain and EC-HC-II increased fat-free mass and grip strength versus some comparators.

Trust comment: Randomized, double-blind human trial directly testing type II collagen hydrolysate; pilot study with moderate sample size and some endpoints lacking detailed effect sizes.

Study Details

PMID:36918892
Participants:151
Impact:EC-HC-II: significantly increased FFM at 24 weeks versus glucosamine (p=0.02) and placebo (p=0.017)
Trust score:4/5

Double-blind randomized placebo-controlled trial (25 men): daily 15 g collagen peptides during 12 weeks resistance training increased absorption marker, fat-free mass, and produced broader proteomic adaptations versus placebo.

Trust comment: Well-designed double-blind randomized placebo-controlled trial with objective biochemical and proteomic endpoints but small sample size.

Study Details

PMID:31091754
Participants:25
Impact:Significantly greater gains in COL vs PLA over 12 weeks (p≤0.05)
Trust score:4/5

Twelve weeks of resistance training plus 15 g/day specific collagen peptides increased fat-free mass, reduced fat mass, and improved hand-grip strength more than placebo.

Trust comment: Double-blind, placebo-controlled randomized trial with adequate sample, supervised training, and consistent PP/ITT results; high internal validity.

Study Details

PMID:31010031
Participants:77
Impact:+1.0 ± 0.9 kg (TG) vs +0.4 ± 0.9 kg (CG); percentage +1.8% vs +0.9%
Trust score:5/5

Skeletal muscle proteome upregulation

1 evidences

Double-blind randomized placebo-controlled trial (25 men): daily 15 g collagen peptides during 12 weeks resistance training increased absorption marker, fat-free mass, and produced broader proteomic adaptations versus placebo.

Trust comment: Well-designed double-blind randomized placebo-controlled trial with objective biochemical and proteomic endpoints but small sample size.

Study Details

PMID:31091754
Participants:25
Impact:More upregulated proteins in COL (221 unique upregulated vs 44 in PLA) and 192 overrepresented pathways vs 1 in PLA
Trust score:4/5

Maximum urethral closure pressure (MUCP) and functional urethral length (FUL)

1 evidences

Randomized study (30 elderly women) comparing midurethral vs bladder-neck transurethral collagen injections; both improved urethral function and satisfaction with a small advantage for midurethral placement.

Trust comment: Randomized clinical trial with clinical endpoints and 10-month follow-up but small sample and limited detail on long-term durability.

Study Details

PMID:18157642
Participants:30
Impact:MUCP and FUL increased significantly in both groups at 10-month follow-up
Trust score:3/5

Continence rate

1 evidences

Randomized study (30 elderly women) comparing midurethral vs bladder-neck transurethral collagen injections; both improved urethral function and satisfaction with a small advantage for midurethral placement.

Trust comment: Randomized clinical trial with clinical endpoints and 10-month follow-up but small sample and limited detail on long-term durability.

Study Details

PMID:18157642
Participants:30
Impact:Continence: 66.6% (midurethral) vs 60% (bladder neck)
Trust score:3/5

patient satisfaction

4 evidences

Randomised double-blind study comparing porcine/bovine collagen fillers and hyaluronic acid for upper lip wrinkles; all treatments increased lip volume and reduced wrinkles, Perlane showed greatest and most sustained volume.

Trust comment: Randomised double-blind trial with objective 3D measures and reasonable sample size though single-centre.

Study Details

PMID:18986859
Participants:79
Impact:no major difference (trend to lower satisfaction for PRI1/PRI2 at month 9)
Trust score:4/5

Randomized study (30 elderly women) comparing midurethral vs bladder-neck transurethral collagen injections; both improved urethral function and satisfaction with a small advantage for midurethral placement.

Trust comment: Randomized clinical trial with clinical endpoints and 10-month follow-up but small sample and limited detail on long-term durability.

Study Details

PMID:18157642
Participants:30
Impact:Median VAS 8 in both groups with a small advantage for midurethral injections (p=0.012)
Trust score:3/5

Double-blind randomized trial of tretinoin 0.05% lotion vs vehicle (vehicle contained soluble collagen among other hydrators) for chest photorejuvenation; both active and vehicle groups improved similarly by 180 days with mild, transient erythema higher in active at day 90.

Trust comment: Randomized double-blind vehicle-controlled human trial but small sample and vehicle contained collagen, complicating attribution of effects to tretinoin vs vehicle.

Study Details

PMID:35674757
Participants:29
Impact:Similar satisfaction at day 180 (active 2.38±1.15 vs vehicle 2.30±1.16)
Trust score:4/5

RCT comparing no graft, connective tissue graft, and xenogeneic collagen matrix at implant placement; no significant differences in esthetic outcomes or peri-implant health at 12 months.

Trust comment: Randomized trial with 60 patients and 12-month follow-up; well-designed but found no effect of collagen matrix on primary clinical/esthetic outcomes.

Study Details

PMID:29756213
Participants:60
Impact:no significant intergroup differences
Trust score:4/5

Mean root coverage (MRC%) — collagen matrix group

1 evidences

Randomized clinical trial (24 patients) comparing VISTA+A-PRF vs VISTA+collagen matrix: both improved recession outcomes but A-PRF produced larger gains; collagen matrix group showed clinically meaningful but smaller improvements.

Trust comment: Randomized clinical trial with blinded outcome assessment and 6-month follow-up but small sample size limits generalizability.

Study Details

PMID:39806320
Participants:24
Impact:MRC%: 56.59±15.35% at 3 months and 50.09±11.42% at 6 months (collagen matrix)
Trust score:3/5

Recession depth (RD) — collagen matrix group

1 evidences

Randomized clinical trial (24 patients) comparing VISTA+A-PRF vs VISTA+collagen matrix: both improved recession outcomes but A-PRF produced larger gains; collagen matrix group showed clinically meaningful but smaller improvements.

Trust comment: Randomized clinical trial with blinded outcome assessment and 6-month follow-up but small sample size limits generalizability.

Study Details

PMID:39806320
Participants:24
Impact:RD decreased from 2.81±0.40 mm baseline to 1.19±0.37 mm at 3 months and 1.38±0.29 mm at 6 months
Trust score:3/5

Gingival thickness (GT) — collagen matrix group

1 evidences

Randomized clinical trial (24 patients) comparing VISTA+A-PRF vs VISTA+collagen matrix: both improved recession outcomes but A-PRF produced larger gains; collagen matrix group showed clinically meaningful but smaller improvements.

Trust comment: Randomized clinical trial with blinded outcome assessment and 6-month follow-up but small sample size limits generalizability.

Study Details

PMID:39806320
Participants:24
Impact:GT increased to 1.78±0.25 mm at 3 months and 1.77±0.23 mm at 6 months
Trust score:3/5

wound area reduction

1 evidences

Topical bovine type I collagen matrix (WCM) applied once accelerated healing of refractory diabetic foot ulcers compared with daily saline dressings.

Trust comment: Randomized multicenter trial with objective photo-based measures; this report is a retrospective exploratory subset analysis with modest sample size, limiting certainty.

Study Details

PMID:31903299
Participants:41
Impact:WCM: 63% reduction at 4 weeks vs SOC: 38% at 4 weeks (significant)
Trust score:4/5

complete ulcer closure incidence

1 evidences

Topical bovine type I collagen matrix (WCM) applied once accelerated healing of refractory diabetic foot ulcers compared with daily saline dressings.

Trust comment: Randomized multicenter trial with objective photo-based measures; this report is a retrospective exploratory subset analysis with modest sample size, limiting certainty.

Study Details

PMID:31903299
Participants:41
Impact:WCM: 42% (11/26) vs SOC: 27% (4/15) at 12 weeks (nonsignificant)
Trust score:4/5

PDGF release

1 evidences

Topical bovine type I collagen matrix (WCM) applied once accelerated healing of refractory diabetic foot ulcers compared with daily saline dressings.

Trust comment: Randomized multicenter trial with objective photo-based measures; this report is a retrospective exploratory subset analysis with modest sample size, limiting certainty.

Study Details

PMID:31903299
Participants:41
Impact:Dose-dependent increase in PDGF release from human platelets (in vitro)
Trust score:4/5

recession depth (gain from baseline)

1 evidences

Collagen matrix + flap gave slightly less root coverage than connective tissue graft + flap but similar esthetic satisfaction and keratinized tissue gains.

Trust comment: Randomized, single-masked split-mouth RCT with 1-year follow-up but small sample (n=25).

Study Details

PMID:20350159
Participants:25
Impact:CM+CAF +2.62 mm; CTG+CAF +3.10 mm (difference 0.48 mm favoring CTG, P=0.0062)
Trust score:4/5

percent root coverage (1 year)

1 evidences

Collagen matrix + flap gave slightly less root coverage than connective tissue graft + flap but similar esthetic satisfaction and keratinized tissue gains.

Trust comment: Randomized, single-masked split-mouth RCT with 1-year follow-up but small sample (n=25).

Study Details

PMID:20350159
Participants:25
Impact:CM+CAF 88.5%; CTG+CAF 99.3% (P=0.0313)
Trust score:4/5

keratinized tissue width gain

1 evidences

Collagen matrix + flap gave slightly less root coverage than connective tissue graft + flap but similar esthetic satisfaction and keratinized tissue gains.

Trust comment: Randomized, single-masked split-mouth RCT with 1-year follow-up but small sample (n=25).

Study Details

PMID:20350159
Participants:25
Impact:CM+CAF +1.34 mm; CTG+CAF +1.26 mm (P=0.9061, no difference)
Trust score:4/5

percent root coverage (6 months)

1 evidences

Adding enamel matrix derivative to a collagen membrane did not improve root coverage outcomes compared with collagen membrane alone at 6 months.

Trust comment: Randomized controlled trial with clear clinical endpoints and 6-month follow-up but modest sample size (n=26).

Study Details

PMID:15633319
Participants:26
Impact:GTRC (collagen) 75%; EMDC (collagen+EMD) 63% (no statistical advantage for EMDC)
Trust score:4/5

recession depth and width

1 evidences

Adding enamel matrix derivative to a collagen membrane did not improve root coverage outcomes compared with collagen membrane alone at 6 months.

Trust comment: Randomized controlled trial with clear clinical endpoints and 6-month follow-up but modest sample size (n=26).

Study Details

PMID:15633319
Participants:26
Impact:Both groups showed significant decreases from baseline to 6 months (P<0.05), with no difference between groups
Trust score:4/5

relative clinical attachment level (RCAL)

1 evidences

Adding enamel matrix derivative to a collagen membrane did not improve root coverage outcomes compared with collagen membrane alone at 6 months.

Trust comment: Randomized controlled trial with clear clinical endpoints and 6-month follow-up but modest sample size (n=26).

Study Details

PMID:15633319
Participants:26
Impact:Significant gain in both groups from baseline to 6 months (P<0.05)
Trust score:4/5

subjective ankle stability (CAIT)

1 evidences

Daily 5 g specific collagen peptides for 6 months improved athletes' self-reported ankle function and reduced re-injury rate, without changing measured mechanical stiffness.

Trust comment: Randomized, double-blind, placebo-controlled trial with 6-month intervention and reasonable sample size (n=50); outcomes largely subjective.

Study Details

PMID:29769831
Participants:50
Impact:Significant improvement vs placebo (P<0.001)
Trust score:4/5

foot and ankle function (FAAM-G)

1 evidences

Daily 5 g specific collagen peptides for 6 months improved athletes' self-reported ankle function and reduced re-injury rate, without changing measured mechanical stiffness.

Trust comment: Randomized, double-blind, placebo-controlled trial with 6-month intervention and reasonable sample size (n=50); outcomes largely subjective.

Study Details

PMID:29769831
Participants:50
Impact:Significant improvement vs placebo (P<0.001)
Trust score:4/5

ankle mechanical stiffness (arthrometer)

1 evidences

Daily 5 g specific collagen peptides for 6 months improved athletes' self-reported ankle function and reduced re-injury rate, without changing measured mechanical stiffness.

Trust comment: Randomized, double-blind, placebo-controlled trial with 6-month intervention and reasonable sample size (n=50); outcomes largely subjective.

Study Details

PMID:29769831
Participants:50
Impact:No significant change between groups
Trust score:4/5

re-injury rate (3-month follow-up)

1 evidences

Daily 5 g specific collagen peptides for 6 months improved athletes' self-reported ankle function and reduced re-injury rate, without changing measured mechanical stiffness.

Trust comment: Randomized, double-blind, placebo-controlled trial with 6-month intervention and reasonable sample size (n=50); outcomes largely subjective.

Study Details

PMID:29769831
Participants:50
Impact:Significant decline in ankle joint injuries in follow-up (P<0.05)
Trust score:4/5

osteocalcin

2 evidences

In 45 postmenopausal osteopenic women, a 12-week supervised walking program improved function and increased bone turnover markers (P1NP, CTX) with osteocalcin rising in the exercise group; both groups received vitamin D and calcium.

Trust comment: Randomized controlled single-blind trial with objective laboratory outcomes; confounded by universal vitamin D/calcium supplementation and modest sample size.

Study Details

PMID:40259282
Participants:45
Impact:Increased +2.5 ng/ml (exercise; p=0.013); no significant change in control (p=0.362)
Trust score:4/5

In two randomized placebo‑controlled studies in 81 postmenopausal women, bedtime GLP‑2 injections produced a dose‑related reduction in the bone resorption marker s‑CTX and a trend toward increased osteocalcin.

Trust comment: Well‑designed randomized placebo‑controlled studies with biologic markers and adequate sample size support reasonable confidence.

Study Details

PMID:14751571
Participants:81
Impact:increased versus placebo (P = 0.07, borderline)
Trust score:4/5

surgical site infection rate

2 evidences

Use of a gentamicin-impregnated collagen sponge after marsupialization did not reduce infection, hemorrhage, or healing time compared with control.

Trust comment: Prospective randomized trial directly testing a collagen sponge product but small sample and negative findings.

Study Details

PMID:25711716
Participants:50
Impact:no significant difference between groups
Trust score:3/5

A gentamicin-collagen implant used during CABG slightly lowered sternal wound infections but the differences were not statistically significant.

Trust comment: Large randomized trial with clear outcomes but reported differences were not statistically significant.

Study Details

PMID:17931241
Participants:542
Impact:4.0% (11/272) vs 5.9% (16/270); -1.9 percentage points, not statistically significant (P=0.20)
Trust score:4/5

mediastinitis rate

2 evidences

A gentamicin-collagen implant used during CABG slightly lowered sternal wound infections but the differences were not statistically significant.

Trust comment: Large randomized trial with clear outcomes but reported differences were not statistically significant.

Study Details

PMID:17931241
Participants:542
Impact:1.1% vs 1.9%; -0.8 percentage points, not statistically significant (P=0.47)
Trust score:4/5

Randomized study of gentamicin-collagen implant vs control in CABG patients showed a small, nonsignificant reduction in sternal wound infections and mediastinitis with the implant; treatment was safe.

Trust comment: Large randomized trial with objective clinical endpoints, but effect was small and not statistically significant and authors note limited power for definitive conclusions.

Study Details

PMID:15620444
Participants:542
Impact:1.1% (implant) vs 1.9% (control); no significant difference
Trust score:3/5

PICP (procollagen type I C‑terminal propeptide)

2 evidences

In a randomized study of 47 hips, two bone cements showed similar clinical performance; collagen‑related bone turnover markers (PICP, ICTP) rose similarly after surgery at 6 weeks and 6 months.

Trust comment: Randomized clinical comparison with 5‑year follow‑up; biomarker changes reported but magnitude not fully specified in provided text.

Study Details

PMID:11817871
Participants:47
Impact:Increase at 6 weeks and 6 months after operation (magnitude not specified) vs baseline
Trust score:3/5

Among older adults at risk for heart failure, diabetes was associated with altered collagen biomarkers and diastolic function; spironolactone had modest short-term effects on collagen turnover markers but no major differential long-term effects by diabetes/CAD status.

Trust comment: Randomized, multicentre trial with validated biomarker assays and moderate sample size; post-hoc subgroup analysis limits causal inferences.

Study Details

PMID:40057728
Participants:495
Impact:−6.97 µg/L (DM+/CAD- vs DM-/CAD+); −9.04 µg/L (DM+/CAD+ vs DM-/CAD+) (baseline, adjusted beta)
Trust score:4/5

bone mineral density (BMD)

3 evidences

Adults with GH deficiency had reduced BMD in some subgroups; GH replacement increased bone turnover over 12 months.

Trust comment: Moderate-size clinical study with objective BMD and biochemical markers; randomized short blind phase then open-label continuation—reasonable quality though some open-label data.

Study Details

PMID:7655642
Participants:64
Impact:reduced at baseline in adult-onset women and childhood-onset men (statistically significant vs controls)
Trust score:3/5

Randomized trial in 120 children (9–12 y): a protein-rich multi-nutrient drink plus rope-skipping attenuated seasonal forearm BMD loss vs rope-skipping alone and modulated PTH and IGF-1 changes.

Trust comment: Randomized controlled trial in children with clear effects on BMD and serum markers, but intervention combined multiple proteins including collagen peptides so effects cannot be attributed specifically to collagen.

Study Details

PMID:39991811
Participants:120
Impact:+0.023 g cm^-2 (relative change; smaller reduction vs control, P=0.037)
Trust score:3/5

In AGHD patients receiving GH replacement, adding oral phosphate or alendronate increased markers of bone activity and produced greater BMD increases compared with GH alone; vitamin D was not studied.

Trust comment: Randomized clinical study with objective BMD and biochemical endpoints but moderate sample size and complex group structure.

Study Details

PMID:21252245
Participants:44
Impact:greater increases with GHR + phosphate or GHR + alendronate (greatest with phosphate; P < 0.01 vs GHR)
Trust score:3/5

complete wound closure rate (hard-to-heal wounds) at 8 weeks

1 evidences

Graftskin plus compression healed venous ulcers faster and more often than compression alone in a randomized multicenter trial; study concerns a bioengineered skin product rather than collagen supplementation.

Trust comment: Large prospective randomized multicenter trial showing clear clinical benefit, but the intervention is a tissue-engineered product rather than oral collagen supplementation.

Study Details

PMID:11074998
Participants:240
Impact:32% vs 10% (+22 percentage points, P=0.008)
Trust score:3/5

complete wound closure rate at 24 weeks

1 evidences

Graftskin plus compression healed venous ulcers faster and more often than compression alone in a randomized multicenter trial; study concerns a bioengineered skin product rather than collagen supplementation.

Trust comment: Large prospective randomized multicenter trial showing clear clinical benefit, but the intervention is a tissue-engineered product rather than oral collagen supplementation.

Study Details

PMID:11074998
Participants:240
Impact:47% vs 19% (+28 percentage points, P=0.002)
Trust score:3/5

uncorrected distance visual acuity (UDVA)

5 evidences

Corneal collagen crosslinking improved vision and corneal curvature over one year versus sham (riboflavin alone), with many patients gaining lines of vision and mean K values decreasing.

Trust comment: Prospective randomized controlled trial with a sham control and reasonable sample size; well-reported clinical outcomes.

Study Details

PMID:21183110
Participants:71
Impact:improved from 0.84 to 0.77 logMAR (P = .04)
Trust score:4/5

Corneal collagen cross-linking improved vision and reduced corneal curvature at 6 months versus sham, with expected cellular changes on confocal microscopy.

Trust comment: Prospective randomized sham-controlled trial with objective measures and 6-month follow-up; moderate sample size (43 eyes).

Study Details

PMID:25708282
Participants:43
Impact:improved by mean 0.11 ± 0.06 logMAR at 6 months (P = 0.01)
Trust score:4/5

Clinical trial of corneal collagen cross-linking showing greater corneal flattening and vision improvement when the ectatic cone was centrally located.

Trust comment: Prospective randomized controlled clinical trial with 99 eyes/76 patients and quantitative outcomes; good quality for clinical intervention.

Study Details

PMID:22692521
Participants:76
Impact:improved overall ≈ -0.08±0.25 logMAR
Trust score:4/5

Adding intrastromal collagen cross-linking to hyperopic LASIK reduced long-term regression and gave better uncorrected vision than LASIK alone at 2 years.

Trust comment: Contralateral randomized human study with 2-year follow-up and objective refractive outcomes, though sample is modest.

Study Details

PMID:23447898
Participants:34
Impact:mean UDVA 0.95 (CXL) vs 0.85 (no CXL) at 2 years
Trust score:4/5

In 179 subjects with post-refractive corneal ectasia, corneal collagen crosslinking (CXL) reduced progression and improved vision at 1 year versus sham.

Trust comment: Prospective, randomized, multicenter controlled trial with substantial sample size and clear clinically meaningful endpoints.

Study Details

PMID:28655538
Participants:179
Impact:mean improvement ≈ +4.5 logMAR letters
Trust score:5/5

seroma magnitude

1 evidences

Applying fibrin glue plus a collagen patch after axillary lymphadenectomy reduced seroma size and duration and reduced required evacuative punctures.

Trust comment: Controlled clinical trial with 25 vs 25 patients showing statistically significant effects; moderate sample and likely non-blinded.

Study Details

PMID:18639659
Participants:50
Impact:decreased (P = 0.004)
Trust score:3/5

seroma duration

1 evidences

Applying fibrin glue plus a collagen patch after axillary lymphadenectomy reduced seroma size and duration and reduced required evacuative punctures.

Trust comment: Controlled clinical trial with 25 vs 25 patients showing statistically significant effects; moderate sample and likely non-blinded.

Study Details

PMID:18639659
Participants:50
Impact:decreased (P = 0.02)
Trust score:3/5

number of evacuative punctures

1 evidences

Applying fibrin glue plus a collagen patch after axillary lymphadenectomy reduced seroma size and duration and reduced required evacuative punctures.

Trust comment: Controlled clinical trial with 25 vs 25 patients showing statistically significant effects; moderate sample and likely non-blinded.

Study Details

PMID:18639659
Participants:50
Impact:fewer punctures in treatment group (statistically significant)
Trust score:3/5

time to ambulation

1 evidences

Multicenter randomized trial showing a percutaneous collagen hemostasis device substantially reduced puncture-site hemostasis time and shortened time to ambulation versus manual compression, without increasing major complications.

Trust comment: Large multicenter randomized trial with clear, clinically relevant endpoints; some subgroup complexity but overall reliable.

Study Details

PMID:10745611
Participants:165
Impact:13.3 h vs 19.2 h (≈−5.9 h; ≈−30.7%; P<0.05)
Trust score:4/5

keratinized peri-implant mucosa (PIKM) increase

1 evidences

In peri-implantitis surgery, both collagen matrix and autologous free gingival grafts reduced pocket depth and bleeding; autologous grafts produced greater keratinized mucosa gain at 3 years.

Trust comment: Dual-center randomized controlled trial with 3‑year follow-up, blinded assessors and intention-to-treat analysis; moderate sample size with some loss to follow-up.

Study Details

PMID:40542468
Participants:41
Impact:+1.0 mm (CM) and +2.0 mm (FGG) at 36 months
Trust score:4/5

intraocular pressure

4 evidences

The biodegradable collagen implant (Ologen) provided similar long-term intraocular pressure control to mitomycin-C, with higher bleb height and no observed adverse reaction.

Trust comment: Randomized 24-month clinical trial with relevant clinical endpoints, though sample size is modest.

Study Details

PMID:21921953
Participants:40
Impact:Mean IOP at endpoint: MMC 16.0 ±2.9 mmHg vs OLO 16.5 ±2.1 mmHg; both significantly reduced vs baseline, no difference between groups
Trust score:4/5

A collagen-based Ologen implant provided similar intraocular pressure control and complication rates as mitomycin‑C over 12 months after trabeculectomy.

Trust comment: Randomised surgical comparison with 12‑month followup but modest sample size (60) limits precision.

Study Details

PMID:23113645
Participants:60
Impact:no significant difference (19.33 vs 19.87 mmHg at 12 months)
Trust score:3/5

In 33 children, adding Ologen (a collagen matrix) to Ahmed valve implantation lowered intraocular pressure more than valve alone over follow-up without added safety issues.

Trust comment: Prospective randomized split (33 eyes) with good follow-up; small sample limits precision but design is strong and Ologen is a collagen matrix.

Study Details

PMID:36100118
Participants:33
Impact:decreased (significant); greater reduction with Ologen vs AGV alone
Trust score:4/5

Randomized study of nonpenetrating deep sclerectomy with a collagen implant, comparing adjunctive mitomycin C versus no MMC in glaucoma patients.

Trust comment: Small randomized trial (n=26) with 24-month follow-up but limited sample size reduces generalizability.

Study Details

PMID:14750756
Participants:26
Impact:decreased 48% in MMC group vs 35% in control at 12 months (48% vs 32% at 24 months)
Trust score:3/5

postoperative complications

2 evidences

Reinforcing anterior colporrhaphy with a bovine pericardium (collagen) graft did not result in a statistically significant improvement in anterior vaginal wall support at 1- or 2-year follow-up.

Trust comment: Randomized trial in women directly testing a collagen (bovine pericardium) graft with moderate follow-up and incomplete longer-term retention of participants.

Study Details

PMID:19546759
Participants:72
Impact:low and similar between groups
Trust score:4/5

A collagen-based Ologen implant provided similar intraocular pressure control and complication rates as mitomycin‑C over 12 months after trabeculectomy.

Trust comment: Randomised surgical comparison with 12‑month followup but modest sample size (60) limits precision.

Study Details

PMID:23113645
Participants:60
Impact:no significant difference between groups
Trust score:3/5

disease activity (clinical variables)

1 evidences

Adding low‑dose oral bovine type II collagen to existing rheumatoid arthritis therapy did not improve outcomes versus placebo over 6 months.

Trust comment: Large (n=190) double‑blind, placebo‑controlled randomized trial showing no clinical benefit of oral type II collagen.

Study Details

PMID:10366113
Participants:190
Impact:no improvement with collagen; several measures favored placebo
Trust score:4/5

complete healing rate

1 evidences

EpiFix (dehydrated amnion/chorion containing collagen and growth factors) produced faster and higher rates of complete healing and lower product costs than Apligraf or standard care in diabetic foot ulcers.

Trust comment: Randomised multi‑centre trial with blinded adjudication and statistically significant results, though sample size per arm was small (n=20 each).

Study Details

PMID:25424146
Participants:60
Impact:EpiFix 95% at 6 weeks vs Apligraf 45% and standard care 35%
Trust score:4/5

treatment cost per patient

1 evidences

EpiFix (dehydrated amnion/chorion containing collagen and growth factors) produced faster and higher rates of complete healing and lower product costs than Apligraf or standard care in diabetic foot ulcers.

Trust comment: Randomised multi‑centre trial with blinded adjudication and statistically significant results, though sample size per arm was small (n=20 each).

Study Details

PMID:25424146
Participants:60
Impact:EpiFix $1,669 vs Apligraf $9,216 (≈81.9% lower cost)
Trust score:4/5

early wound‑healing rate

1 evidences

A single application of formulated collagen gel increased early wound‑healing rates in neuropathic diabetic foot ulcers during the first 1–2 weeks compared with standard care, though final closure rates were not significantly different in this exploratory Phase 2 trial.

Trust comment: Phase 2 multicentre randomized trial with objective improvements in early healing but exploratory analyses and measurement issues reduced certainty.

Study Details

PMID:21371164
Participants:116
Impact:FCG Day1–Week1: +1.97 mm/week vs SOC 0.78 mm/week (significant increase)
Trust score:3/5

complete closure incidence

1 evidences

A single application of formulated collagen gel increased early wound‑healing rates in neuropathic diabetic foot ulcers during the first 1–2 weeks compared with standard care, though final closure rates were not significantly different in this exploratory Phase 2 trial.

Trust comment: Phase 2 multicentre randomized trial with objective improvements in early healing but exploratory analyses and measurement issues reduced certainty.

Study Details

PMID:21371164
Participants:116
Impact:FCG 35% vs SOC 31% at 12 weeks (not statistically significant)
Trust score:3/5

total collagen content

2 evidences

Six months of oestradiol in postmenopausal women decreased total vaginal collagen and markers of aged collagen while increasing immature cross-links and MMP-2 expression, indicating stimulated collagen turnover.

Trust comment: Double-blind placebo-controlled biopsy study with clear biochemical endpoints and good completion rate (49 of 55), providing reliable evidence on collagen metabolism.

Study Details

PMID:11950190
Participants:49
Impact:decreased with oestradiol versus placebo (P=0.0054)
Trust score:4/5

Tissue from cesarean hysterotomy edges was compared; the lower edge had higher collagen content but similar biomechanical properties to the upper edge.

Trust comment: Prospective randomized surgical study on 40 women with biochemical and biomechanical measures; moderate sample but clear measurements.

Study Details

PMID:17329522
Participants:40
Impact:higher in lower edge of hysterotomy (P<.001)
Trust score:4/5

collagen cross-linking (pyridinoline-to-collagen ratio)

1 evidences

Tissue from cesarean hysterotomy edges was compared; the lower edge had higher collagen content but similar biomechanical properties to the upper edge.

Trust comment: Prospective randomized surgical study on 40 women with biochemical and biomechanical measures; moderate sample but clear measurements.

Study Details

PMID:17329522
Participants:40
Impact:decreased in lower edge (P<.001)
Trust score:4/5

biomechanical tensile properties

1 evidences

Tissue from cesarean hysterotomy edges was compared; the lower edge had higher collagen content but similar biomechanical properties to the upper edge.

Trust comment: Prospective randomized surgical study on 40 women with biochemical and biomechanical measures; moderate sample but clear measurements.

Study Details

PMID:17329522
Participants:40
Impact:no significant difference between upper and lower edges (no change)
Trust score:4/5

scar severity (Goodman and Baron)

1 evidences

Split-face study: fractional CO2 laser + PRP versus hyaluronic acid showed significant clinical improvement on both sides; histology showed increased collagen and elastic fibers, more favorable with PRP.

Trust comment: Split-face randomized design with 30 patients and histology in subset (n=6); moderate-quality cosmetic study but limited sample and follow-up.

Study Details

PMID:32333512
Participants:30
Impact:significant reduction on both sides after treatment (P<0.05)
Trust score:3/5

collagen and elastic fiber content

1 evidences

Split-face study: fractional CO2 laser + PRP versus hyaluronic acid showed significant clinical improvement on both sides; histology showed increased collagen and elastic fibers, more favorable with PRP.

Trust comment: Split-face randomized design with 30 patients and histology in subset (n=6); moderate-quality cosmetic study but limited sample and follow-up.

Study Details

PMID:32333512
Participants:30
Impact:increased in both treatments; greater increase on PRP-treated side (histopathology)
Trust score:3/5

new bone formation

1 evidences

Using DBBM plus a porcine collagen membrane or matrix resulted in less new bone formation at 4 months than unassisted socket healing.

Trust comment: Randomized allocation with histomorphometric endpoints and objective measurements gives moderate-high reliability.

Study Details

PMID:39105326
Participants:42
Impact:Control (unassisted): 45.89% ±11.48; GBR (DBBM+porcine collagen membrane): 22.12% ±12.7; SS (DBBM+porcine collagen matrix): 27.62% ±17.76
Trust score:4/5

urine C-telopeptides of type I collagen

1 evidences

In postmenopausal women, higher ibandronate exposure was associated with larger reductions in bone turnover markers (including collagen C-telopeptides) and greater spine BMD response at 12 months.

Trust comment: Phase II clinical trial with pharmacokinetic and biomarker associations and reasonable completer numbers, supporting valid associations.

Study Details

PMID:11792604
Participants:116
Impact:decrease correlated with AUC(0-6h ss), r = -0.65, p<0.0001
Trust score:4/5

serum C-telopeptides of type I collagen

1 evidences

In postmenopausal women, higher ibandronate exposure was associated with larger reductions in bone turnover markers (including collagen C-telopeptides) and greater spine BMD response at 12 months.

Trust comment: Phase II clinical trial with pharmacokinetic and biomarker associations and reasonable completer numbers, supporting valid associations.

Study Details

PMID:11792604
Participants:116
Impact:decrease correlated with AUC(0-6h ss), r = -0.65, p<0.0001
Trust score:4/5

spine bone mineral density (BMD)

3 evidences

Once-weekly alendronate significantly increased bone mineral density and reduced bone turnover markers versus calcium alone over one year.

Trust comment: Randomized trial in 58 women with clear, clinically relevant BMD and biomarker outcomes, but modest sample size.

Study Details

PMID:16076919
Participants:58
Impact:+6.1% at 12 months
Trust score:4/5

In postmenopausal women, higher ibandronate exposure was associated with larger reductions in bone turnover markers (including collagen C-telopeptides) and greater spine BMD response at 12 months.

Trust comment: Phase II clinical trial with pharmacokinetic and biomarker associations and reasonable completer numbers, supporting valid associations.

Study Details

PMID:11792604
Participants:116
Impact:increase correlated with AUC(0-6h ss), r = 0.39, p<0.0001
Trust score:4/5

Long-term alfacalcidol (vitamin D analog) increased bone mineral density at spine and hip and lowered parathyroid hormone and bone turnover markers in pre-dialysis CRF patients.

Trust comment: Randomized, double-blind, placebo-controlled trial but small sample size (n=36) limits precision despite clear biochemical and BMD effects.

Study Details

PMID:15031343
Participants:36
Impact:+4.2% vs placebo
Trust score:4/5

durability of correction

1 evidences

Bovine collagen dermal filler provided shorter-lasting nasolabial fold correction than newer HA fillers; most subjects preferred HA.

Trust comment: Large, multicenter, double-masked within-subject randomized study with clear endpoints, supporting good reliability.

Study Details

PMID:18086050
Participants:439
Impact:Bovine collagen less durable than HA (HA: 81–90% of treated NLFs maintained improvement ≥6 months)
Trust score:4/5

patient preference

1 evidences

Bovine collagen dermal filler provided shorter-lasting nasolabial fold correction than newer HA fillers; most subjects preferred HA.

Trust comment: Large, multicenter, double-masked within-subject randomized study with clear endpoints, supporting good reliability.

Study Details

PMID:18086050
Participants:439
Impact:Up to 88% of subjects preferred HA over bovine collagen
Trust score:4/5

new bone contour

1 evidences

Bio-Oss powder and Bio-Oss collagen produced similar site preservation outcomes after tooth extraction.

Trust comment: Small randomized comparison (n=26) with limited sample size and mixed reporting of statistical details; moderate reliability.

Study Details

PMID:33089293
Participants:26
Impact:No significant difference between Bio-Oss powder and Bio-Oss collagen
Trust score:3/5

alveolar bone height/width/density

1 evidences

Bio-Oss powder and Bio-Oss collagen produced similar site preservation outcomes after tooth extraction.

Trust comment: Small randomized comparison (n=26) with limited sample size and mixed reporting of statistical details; moderate reliability.

Study Details

PMID:33089293
Participants:26
Impact:Overall no significant difference in efficacy between materials
Trust score:3/5

minor local complications

1 evidences

Percutaneous collagen device (VasoSeal) achieved faster hemostasis but had more minor local complications and lower technical success than mechanical compression.

Trust comment: Randomized comparative clinical study with clear outcome measures but modest sample size; moderate quality.

Study Details

PMID:12743862
Participants:57
Impact:VasoSeal 34.6% vs Compressar 5.8% (higher with VasoSeal)
Trust score:3/5

technical success

1 evidences

Percutaneous collagen device (VasoSeal) achieved faster hemostasis but had more minor local complications and lower technical success than mechanical compression.

Trust comment: Randomized comparative clinical study with clear outcome measures but modest sample size; moderate quality.

Study Details

PMID:12743862
Participants:57
Impact:VasoSeal 81% vs Compressar 100%
Trust score:3/5

DFU size reduction at 4 weeks

1 evidences

A collagen-chitosan matrix dressing sped healing of hard-to-heal diabetic foot ulcers compared with saline-moistened gauze.

Trust comment: Randomized controlled trial with clinically meaningful endpoints and clear differences, though open-label; reasonably reliable.

Study Details

PMID:32160125
Participants:61
Impact:Collagen dressing 54.5% reduction vs control 38.8%
Trust score:4/5

complete healing rate at 20 weeks

1 evidences

A collagen-chitosan matrix dressing sped healing of hard-to-heal diabetic foot ulcers compared with saline-moistened gauze.

Trust comment: Randomized controlled trial with clinically meaningful endpoints and clear differences, though open-label; reasonably reliable.

Study Details

PMID:32160125
Participants:61
Impact:Collagen dressing 60% vs control 35.5%
Trust score:4/5

small hematoma rate

1 evidences

Collagen plug (VasoSeal) after PTCA markedly shortened time to hemostasis but overall local complication rates were similar, with a possible increase in large hematomas.

Trust comment: Prospective, randomized study with adequate sample size (n=150) and clear endpoints, though rare complications had low event counts.

Study Details

PMID:9554769
Participants:150
Impact:-9 percentage points (23% vs 32%) with collagen
Trust score:4/5

large hematoma rate

1 evidences

Collagen plug (VasoSeal) after PTCA markedly shortened time to hemostasis but overall local complication rates were similar, with a possible increase in large hematomas.

Trust comment: Prospective, randomized study with adequate sample size (n=150) and clear endpoints, though rare complications had low event counts.

Study Details

PMID:9554769
Participants:150
Impact:+4 percentage points (4% vs 0%) with collagen
Trust score:4/5

Integra take rate

1 evidences

Using a collagen-containing dermal matrix (Integra) with negative pressure wound therapy improved graft take and shortened time to definitive coverage versus Integra alone.

Trust comment: Randomized clinical study but small sample (n=36); outcomes significant but limited generalizability due to size.

Study Details

PMID:33433246
Participants:36
Impact:+~12 percentage points higher take rate with NPWT (p<0.001; 95% CI ~11.24–13.18)
Trust score:3/5

time from Integra coverage to skin transplantation

1 evidences

Using a collagen-containing dermal matrix (Integra) with negative pressure wound therapy improved graft take and shortened time to definitive coverage versus Integra alone.

Trust comment: Randomized clinical study but small sample (n=36); outcomes significant but limited generalizability due to size.

Study Details

PMID:33433246
Participants:36
Impact:decreased (shorter time with NPWT; p<0.001)
Trust score:3/5

Hospital length of stay

3 evidences

In elective colorectal surgery, adding a gentamicin-collagen sponge to systemic antibiotics lowered postoperative wound infection rates compared with systemic antibiotics alone.

Trust comment: Randomized clinical trial with clear clinically meaningful reduction in wound infections; robust sample though older single-study result.

Study Details

PMID:9167147
Participants:221
Impact:mean 13.8 days (sponge) vs 16.3 days (control); not statistically significant
Trust score:4/5

Randomized double-blind pilot trial in men with 20–30% TBSA burns testing an oral hydrolyzed collagen supplement versus isocaloric placebo for 4 weeks; supplement improved markers and wound-healing rate.

Trust comment: Randomized double-blind human pilot trial with objective biochemical and clinical endpoints, though small and limited to men.

Study Details

PMID:31859087
Participants:31
Impact:9.4 vs 13.5 days (collagen shorter, P=0.063, not statistically significant)
Trust score:4/5

Using a collagen-containing dermal matrix (Integra) with negative pressure wound therapy improved graft take and shortened time to definitive coverage versus Integra alone.

Trust comment: Randomized clinical study but small sample (n=36); outcomes significant but limited generalizability due to size.

Study Details

PMID:33433246
Participants:36
Impact:decreased (shorter with NPWT)
Trust score:3/5

serum C-telopeptide (CTX) — 150 mg arm

1 evidences

Once-monthly oral ibandronate substantially reduced bone resorption markers over 3 months and was well tolerated compared with placebo.

Trust comment: Randomized, double-blind, placebo-controlled phase I study with robust biomarker reductions but short duration.

Study Details

PMID:15972582
Participants:144
Impact:-56.7% at day 91
Trust score:4/5

urinary CTX — 150 mg arm

1 evidences

Once-monthly oral ibandronate substantially reduced bone resorption markers over 3 months and was well tolerated compared with placebo.

Trust comment: Randomized, double-blind, placebo-controlled phase I study with robust biomarker reductions but short duration.

Study Details

PMID:15972582
Participants:144
Impact:-54.1% at day 91
Trust score:4/5

incidence of complete wound closure

1 evidences

rbFGF on an absorbable collagen sponge increased closure rates and sped healing of chronic traumatic ulcers without more side effects.

Trust comment: Double-blind randomized controlled trial with clear endpoints and significant effects, but modest sample size.

Study Details

PMID:18458383
Participants:58
Impact:+68% (90.0% vs 53.6%)
Trust score:4/5

time to complete wound closure

2 evidences

A skin graft product containing a collagen matrix helped long-standing venous leg ulcers heal faster and in more people than standard compression alone.

Trust comment: Randomized, prospective controlled trial with clear outcomes and reasonable sample size (n=120), supporting moderate-high trust.

Study Details

PMID:10781211
Participants:120
Impact:shorter (median time to closure improved; p < 0.005)
Trust score:4/5

rbFGF on an absorbable collagen sponge increased closure rates and sped healing of chronic traumatic ulcers without more side effects.

Trust comment: Double-blind randomized controlled trial with clear endpoints and significant effects, but modest sample size.

Study Details

PMID:18458383
Participants:58
Impact:-24% (10.6 days vs 13.9 days)
Trust score:4/5

healing quality

1 evidences

rbFGF on an absorbable collagen sponge increased closure rates and sped healing of chronic traumatic ulcers without more side effects.

Trust comment: Double-blind randomized controlled trial with clear endpoints and significant effects, but modest sample size.

Study Details

PMID:18458383
Participants:58
Impact:improved (qualitative; no numeric provided)
Trust score:4/5

wrinkle correction (nasolabial folds)

1 evidences

ArteFill (PMMA microspheres + bovine collagen) produced greater wrinkle correction than collagen filler at 6 months and durable improvement to 4–5 years with low late adverse-event rates.

Trust comment: Pivotal multicenter FDA trial with 251 subjects and long-term follow-up, though long-term data derive from a smaller recalled subgroup.

Study Details

PMID:16936546
Participants:251
Impact:significant improvement at 6 months vs collagen (p < 0.001)
Trust score:4/5

long-term improvement

1 evidences

ArteFill (PMMA microspheres + bovine collagen) produced greater wrinkle correction than collagen filler at 6 months and durable improvement to 4–5 years with low late adverse-event rates.

Trust comment: Pivotal multicenter FDA trial with 251 subjects and long-term follow-up, though long-term data derive from a smaller recalled subgroup.

Study Details

PMID:16936546
Participants:251
Impact:+1.67 points (investigator rating at 4–5 years vs baseline)
Trust score:4/5

late adverse events (wrinkles injected)

1 evidences

ArteFill (PMMA microspheres + bovine collagen) produced greater wrinkle correction than collagen filler at 6 months and durable improvement to 4–5 years with low late adverse-event rates.

Trust comment: Pivotal multicenter FDA trial with 251 subjects and long-term follow-up, though long-term data derive from a smaller recalled subgroup.

Study Details

PMID:16936546
Participants:251
Impact:2.2% overall late events (6/272 wrinkles); severe 0.7% (2/272)
Trust score:4/5

fat mass

1 evidences

Daily 15 g specific collagen peptides plus 12-week resistance training increased fat-free mass and reduced fat mass more than placebo in overweight middle-aged men.

Trust comment: Double-blind, randomized, placebo-controlled trial with objective DXA and strength measures; per-protocol sample moderate.

Study Details

PMID:33946565
Participants:61
Impact:−5.28 kg (CP) vs −3.39 kg (placebo); greater reduction with collagen (P = 0.023)
Trust score:4/5

C-reactive protein (CRP)

2 evidences

Sixty patients receiving either gelatin-sealed (Gelseal) or collagen-sealed (Hemashield) aortic grafts: gelatin group showed higher leukocyte counts in the second week, differences resolved by day 21.

Trust comment: Randomized prospective trial in 60 patients comparing collagen-sealed vs gelatin-sealed grafts with serial inflammatory markers; moderate-high quality.

Study Details

PMID:9219480
Participants:60
Impact:no consistent difference between groups
Trust score:4/5

Randomized comparison of femoral closure devices including AngioSeal (anchor + collagen sponge) showed no device-related differences in systemic inflammatory markers; IL-6 rose at 6 hours in all groups.

Trust comment: Randomized study with biomarker endpoints and adequate reporting showing no device-specific systemic inflammatory effect.

Study Details

PMID:18398639
Participants:77
Impact:no between-group change; no sustained increase at 30 days
Trust score:4/5

pain score

1 evidences

Using a collagen plug after catheterization shortened bleeding time and caused less pain with similar complication rates.

Trust comment: Randomized study with objective measures and duplex follow-up; moderate sample size supports findings.

Study Details

PMID:9040266
Participants:62
Impact:decrease with collagen plug vs manual compression (P=0.01)
Trust score:4/5

bone-specific alkaline phosphatase (bone ALP)

1 evidences

Five years of risedronate reduced bone turnover markers and increased lumbar spine BMD, with no pathologic biopsy findings.

Trust comment: Extension randomized/controlled data with paired biopsies and multiple objective bone markers; moderate sample for biopsy analyses.

Study Details

PMID:15478000
Participants:48
Impact:−33.3% from baseline (risedronate)
Trust score:4/5

spine BMD

1 evidences

Postmenopausal women received varying doses of ibandronate; higher doses increased BMD and reduced biochemical markers of bone turnover including type I collagen breakdown products.

Trust comment: Randomized, double-blind controlled trial with clear biochemical and BMD endpoints, though multi-dose design complicates single-dose interpretation.

Study Details

PMID:8922653
Participants:141
Impact:increased (+4.6% ±3.1% in 2.5 mg group, p<0.001)
Trust score:4/5

spontaneous membrane exposure

1 evidences

Cross-linked collagen membranes persisted longer but had higher exposure rates; non-cross-linked membranes degraded faster and were often undetectable.

Trust comment: Double-blind randomized design with histologic endpoints and clear differences between membrane types.

Study Details

PMID:18190562
Participants:52
Impact:CLM 50% vs NCLM 23.1% (increase, P<0.05)
Trust score:4/5

membrane integrity/persistence

1 evidences

Cross-linked collagen membranes persisted longer but had higher exposure rates; non-cross-linked membranes degraded faster and were often undetectable.

Trust comment: Double-blind randomized design with histologic endpoints and clear differences between membrane types.

Study Details

PMID:18190562
Participants:52
Impact:CLM maintained histologic integrity in non-perforated sites; NCLM undetected in specimens (more degradation)
Trust score:4/5

ossification at/within membrane

1 evidences

Cross-linked collagen membranes persisted longer but had higher exposure rates; non-cross-linked membranes degraded faster and were often undetectable.

Trust comment: Double-blind randomized design with histologic endpoints and clear differences between membrane types.

Study Details

PMID:18190562
Participants:52
Impact:occasional bone apposition/ossification observed with CLM
Trust score:4/5

antibody responses to bovine thrombin/collagen hemostat

1 evidences

Antibody responses after using a bovine‑thrombin/collagen hemostat were similar to expected literature values and were not linked to adverse reactions.

Trust comment: Clinical randomized study with moderate sample size assessing safety of a bovine collagen–containing hemostat; reasonable relevance to collagen product safety.

Study Details

PMID:11745525
Participants:176
Impact:similar to reported literature; no associated adverse reactions at 8‑week follow-up
Trust score:3/5

complete epithelialization (rate/time)

1 evidences

Randomized multicenter study in patients with diabetic foot: adding Collost (collagen biomaterial) to standard therapy improved ulcer healing over 4 weeks.

Trust comment: Randomized multicenter human trial with modest sample (n=71) and short follow-up (4 weeks); results plausible but limited long-term data and limited methodological details.

Study Details

PMID:28374714
Participants:71
Impact:achieved 2.6 times more rapidly in Collost group
Trust score:3/5

incidence of unsuccessful treatment

1 evidences

Randomized multicenter study in patients with diabetic foot: adding Collost (collagen biomaterial) to standard therapy improved ulcer healing over 4 weeks.

Trust comment: Randomized multicenter human trial with modest sample (n=71) and short follow-up (4 weeks); results plausible but limited long-term data and limited methodological details.

Study Details

PMID:28374714
Participants:71
Impact:reduced by 4.1-fold with Collost
Trust score:3/5

foreign body reaction

1 evidences

Randomized trial of trapeziectomy with or without porcine collagen (Permacol) implant; collagen group had frequent adverse reactions and worse clinical outcomes.

Trust comment: Randomized comparative design but small (n=26) and stopped early due to adverse events, limiting precision and generalizability.

Study Details

PMID:11281672
Participants:26
Impact:observed in 6/13 collagen patients; 3 implants removed
Trust score:3/5

grip strength / function

1 evidences

Randomized trial of trapeziectomy with or without porcine collagen (Permacol) implant; collagen group had frequent adverse reactions and worse clinical outcomes.

Trust comment: Randomized comparative design but small (n=26) and stopped early due to adverse events, limiting precision and generalizability.

Study Details

PMID:11281672
Participants:26
Impact:improved only in control group
Trust score:3/5

serum CTx (C-terminal telopeptide of type I collagen)

1 evidences

Risedronate (daily or weekly) markedly lowered bone turnover markers (CTX and bone ALP) over 3–6 months in postmenopausal women with osteoporosis.

Trust comment: Randomized, double-blind controlled trial with adequate sample size and clear biochemical endpoints.

Study Details

PMID:19927782
Participants:102
Impact:−47.6% at 3 months; −62.9% at 6 months
Trust score:4/5

intact PTH

1 evidences

In dialysis patients with early secondary hyperparathyroidism, intermittent intravenous calcitriol prevented parathyroid gland enlargement compared with daily oral calcitriol over 12 months.

Trust comment: Randomized controlled trial (72 randomized, 60 completed) with objective imaging and biochemical outcomes; good internal validity though sample modest.

Study Details

PMID:18515308
Participants:60
Impact:decrease (significant after 1 month in both groups)
Trust score:4/5

lumbar spine bone mineral density

2 evidences

Double-blind randomized study in postmenopausal women: sublingual hormone therapy reduced bone turnover including type I collagen N-telopeptide and increased spine and hip BMD over 12 months.

Trust comment: Double-blind randomized study with clear biomarker and BMD changes though moderate sample size.

Study Details

PMID:10993031
Participants:57
Impact:+2.2% (HRT) and +1.8% (HRT+T)
Trust score:4/5

Bazedoxifene/conjugated estrogens increased spine and hip bone mineral density and reduced bone turnover markers versus placebo in postmenopausal women at risk for osteoporosis.

Trust comment: Large, randomized, double-blind, phase 3 trial providing high-quality evidence for BMD and marker changes.

Study Details

PMID:19635616
Participants:3397
Impact:significant increase versus placebo (all BZA/CE doses)
Trust score:4/5

pain intensity (VAS)

1 evidences

Injecting collagen into masseter trigger points reduced pain and muscle activity more than lidocaine or saline over a 2-week observation.

Trust comment: Randomized, registered single-blind RCT with objective and subjective measures; limited by small sample and short follow-up.

Study Details

PMID:29973970
Participants:43
Impact:-53.75% (mean VAS −4.3 points)
Trust score:4/5

masseter muscle resting sEMG activity

1 evidences

Injecting collagen into masseter trigger points reduced pain and muscle activity more than lidocaine or saline over a 2-week observation.

Trust comment: Randomized, registered single-blind RCT with objective and subjective measures; limited by small sample and short follow-up.

Study Details

PMID:29973970
Participants:43
Impact:-59.2% (−32.9 μV)
Trust score:4/5

upper-limb function (QuickDASH)

1 evidences

Collagen injections (alone or with PRP) and PRP alone all improved pain and function over time, with no clear advantage of collagen over PRP or combined therapy at 24 weeks.

Trust comment: Randomized controlled trial with validated clinical and imaging outcomes; open-label and moderate sample size limit certainty.

Study Details

PMID:36536333
Participants:82
Impact:within-group improvement (p<0.001); no difference vs PRP/combined (p=0.997)
Trust score:4/5

ultrasound-confirmed RC regeneration

1 evidences

Collagen injections (alone or with PRP) and PRP alone all improved pain and function over time, with no clear advantage of collagen over PRP or combined therapy at 24 weeks.

Trust comment: Randomized controlled trial with validated clinical and imaging outcomes; open-label and moderate sample size limit certainty.

Study Details

PMID:36536333
Participants:82
Impact:collagen group: 20/30 showed US-confirmed regeneration; no significant differences between groups
Trust score:4/5

time to wound healing

2 evidences

Use of a gentamicin-containing collagen fleece with primary closure substantially shortened wound healing time versus open treatment.

Trust comment: Randomized multicentre controlled trial showing a large, clinically meaningful effect on healing time.

Study Details

PMID:12780882
Participants:103
Impact:median 17 days (Septocoll) vs 68 days (open) (p=0.0001)
Trust score:4/5

Adding a gentamicin–collagen sponge to primary excision reduced early (1-week) postoperative complications but did not change long-term recurrence.

Trust comment: Large prospective randomized study with clear early outcome differences; good applicability for collagen-based local delivery but some outcomes counterintuitive (healing time).

Study Details

PMID:18093197
Participants:200
Impact:mean healing longer with collagen sponge: 24 vs 21 days (+3 days)
Trust score:4/5

primary wound healing rate

1 evidences

Use of a gentamicin-containing collagen fleece with primary closure substantially shortened wound healing time versus open treatment.

Trust comment: Randomized multicentre controlled trial showing a large, clinically meaningful effect on healing time.

Study Details

PMID:12780882
Participants:103
Impact:73% primary healing in Septocoll group
Trust score:4/5

Stamey grade improvement (≥1 grade)

1 evidences

In this trial Contigen (bovine collagen-based injection) produced improvement in stress urinary incontinence, though Macroplastique outperformed it at 12 months.

Trust comment: Large randomized multicenter single-blind trial with 12-month outcomes; Contigen served as active control.

Study Details

PMID:19013613
Participants:247
Impact:48% improved at 12 months (Contigen group)
Trust score:4/5

dry/cure rate

1 evidences

In this trial Contigen (bovine collagen-based injection) produced improvement in stress urinary incontinence, though Macroplastique outperformed it at 12 months.

Trust comment: Large randomized multicenter single-blind trial with 12-month outcomes; Contigen served as active control.

Study Details

PMID:19013613
Participants:247
Impact:24.8% dry/cure at 12 months (Contigen group)
Trust score:4/5

pad weight decrease (1-hour)

1 evidences

In this trial Contigen (bovine collagen-based injection) produced improvement in stress urinary incontinence, though Macroplastique outperformed it at 12 months.

Trust comment: Large randomized multicenter single-blind trial with 12-month outcomes; Contigen served as active control.

Study Details

PMID:19013613
Participants:247
Impact:−22.8 ml from baseline (Contigen group)
Trust score:4/5

urinary NTx (type I collagen marker)

1 evidences

In 50 elderly men, 6 months of raloxifene showed no overall change in bone turnover or lipids, but reductions in urinary type I collagen NTX occurred in a subset with low baseline estradiol.

Trust comment: Randomized blinded study with clear biomarker outcomes and moderate sample size, but subgroup-dependent effects.

Study Details

PMID:11697809
Participants:50
Impact:decreased in subset of raloxifene-treated men with low baseline estradiol (association r=0.57, p=0.004)
Trust score:4/5

postoperative intraocular pressure (IOP)

1 evidences

Placing an Ologen collagen matrix with Ahmed glaucoma valve implantation lowered early postoperative IOP and reduced the hypertensive phase frequency but did not change long-term success rates.

Trust comment: Randomized controlled trial but small sample (n=26); shows intermediate-term IOP benefits with Ologen collagen matrix but limited power for long-term outcomes.

Study Details

PMID:33338679
Participants:26
Impact:Lower maximum mean postop IOP in Ologen group (16.8 ±8.9 mmHg) vs control (25.2 ±7.4 mmHg) during follow-up (significant at 1–3 months)
Trust score:3/5

horizontal ridge resorption (1 mm from crest)

1 evidences

Three ARP approaches (including use of collagen membrane) produced similar horizontal ridge preservation; some differences in vertical mid-crestal measurements and mucosal thickness were observed.

Trust comment: Randomized clinical trial on humans but small per-group analyzed sample and trial registration occurred late, limiting confidence.

Study Details

PMID:38638057
Participants:56
Impact:Test1 (dPTFE): 1.29 ± 1.37 mm; Test2 (collagen membrane): 1.07 ± 1.07 mm; Control (full graft + collagen): 1.54 ± 1.33 mm (p = 0.328; no significant difference)
Trust score:3/5

vertical mid-crestal bone height change

1 evidences

Three ARP approaches (including use of collagen membrane) produced similar horizontal ridge preservation; some differences in vertical mid-crestal measurements and mucosal thickness were observed.

Trust comment: Randomized clinical trial on humans but small per-group analyzed sample and trial registration occurred late, limiting confidence.

Study Details

PMID:38638057
Participants:56
Impact:Test1: 0.11 ± 1.02 mm; Test2: 0.29 ± 0.83 mm; Control: -0.46 ± 0.95 mm (p = 0.032)
Trust score:3/5

vertical mucosal thickness

1 evidences

Three ARP approaches (including use of collagen membrane) produced similar horizontal ridge preservation; some differences in vertical mid-crestal measurements and mucosal thickness were observed.

Trust comment: Randomized clinical trial on humans but small per-group analyzed sample and trial registration occurred late, limiting confidence.

Study Details

PMID:38638057
Participants:56
Impact:Higher vertical mucosal thickness with dPTFE membrane (Test1: 2.67 ± 0.90 mm) vs Test2 (3.89 ± 1.08 mm) and Control (2.41 ± 0.51 mm) (p < 0.001)
Trust score:3/5

surgical site infection (SSI) rate

1 evidences

Applying gentamicin-collagen sponges or collagen-only sponges to the extraction-site wound did not significantly reduce 30-day surgical site infections compared with no sponge.

Trust comment: Large randomized, double-blind, placebo-controlled human trial; outcome measures clear though no significant benefit found for collagen sponge interventions.

Study Details

PMID:25172200
Participants:291
Impact:GCS 8.2%; collagen-only sponge 13.5%; control (no sponge) 11.3% (no significant differences)
Trust score:4/5

trend toward reduced SSI with GCS

1 evidences

Applying gentamicin-collagen sponges or collagen-only sponges to the extraction-site wound did not significantly reduce 30-day surgical site infections compared with no sponge.

Trust comment: Large randomized, double-blind, placebo-controlled human trial; outcome measures clear though no significant benefit found for collagen sponge interventions.

Study Details

PMID:25172200
Participants:291
Impact:Observed trend: GCS 8.2% vs control 11.3% (not statistically significant; larger trial needed)
Trust score:4/5

residual gingival recession after 18 months

1 evidences

In a split-mouth RCT, xenogeneic collagen matrix (XCM) improved root coverage and quality of life but CTG produced greater final gingival thickness and slightly better root-coverage metrics at 18 months.

Trust comment: Split-mouth, double-blind RCT with 18-month follow-up; moderate sample size but rigorous design supports moderate-high trust.

Study Details

PMID:39536202
Participants:30
Impact:XCM residual recession 0.65 mm (from baseline 2.4 mm); CTG residual 0.3 mm (from baseline 2.7 mm)
Trust score:4/5

structural healing (MRI)

1 evidences

Atelocollagen injections for partial supraspinatus tears provided greater and more sustained pain relief and better MRI-documented structural improvement than prolotherapy at 3 months.

Trust comment: Prospective randomized trial with MRI-confirmed structural outcomes but small sample (34 enrolled, 28 completers) and short follow-up (3 months).

Study Details

PMID:40773637
Participants:28
Impact:4 improved vs 0 improved (atelocollagen vs prolotherapy); aggravated tears 2 vs 10
Trust score:4/5

shoulder function (K-SPADI/SCSS)

1 evidences

Atelocollagen injections for partial supraspinatus tears provided greater and more sustained pain relief and better MRI-documented structural improvement than prolotherapy at 3 months.

Trust comment: Prospective randomized trial with MRI-confirmed structural outcomes but small sample (34 enrolled, 28 completers) and short follow-up (3 months).

Study Details

PMID:40773637
Participants:28
Impact:improved in both groups; no significant between-group difference
Trust score:4/5

root coverage (mean and complete)

1 evidences

Adding a xenogeneic collagen matrix to coronally advanced flap increased gingival thickness but did not improve root coverage versus flap alone at 1 year.

Trust comment: Assessor-blind randomized clinical trial with objective measures (n=24) but modest sample size.

Study Details

PMID:31292987
Participants:24
Impact:no difference between CAF+CMX and CAF alone at 12 months
Trust score:4/5

gingival thickness

3 evidences

Using two types of xenogeneic collagen matrices with bone graft helped maintain soft tissues and limited ridge resorption after tooth extraction, with small increases in gingival thickness.

Trust comment: Randomized controlled prospective study but very small completed sample (n=23), reducing precision and external validity.

Study Details

PMID:26745614
Participants:23
Impact:+0.1 mm (increased from 0.1 to 0.2 mm) after 4 months
Trust score:3/5

Adding a xenogeneic collagen matrix to coronally advanced flap increased gingival thickness but did not improve root coverage versus flap alone at 1 year.

Trust comment: Assessor-blind randomized clinical trial with objective measures (n=24) but modest sample size.

Study Details

PMID:31292987
Participants:24
Impact:increased by ~+0.5 mm (significant, p=0.0057) with CMX
Trust score:4/5

Adding a xenogeneic collagen matrix to coronally advanced flap surgery increased keratinized tissue width and gingival thickness vs flap alone, while root coverage and patient satisfaction were similar at 12 months.

Trust comment: Randomized controlled trial with 45 patients and objective clinical measures; moderate sample size limits power for some outcomes.

Study Details

PMID:27717210
Participants:45
Impact:Gain 0.52 mm (test) vs 0.27 mm (control); p=0.0023
Trust score:4/5

keratinized tissue width & patient-reported outcomes

1 evidences

Adding a xenogeneic collagen matrix to coronally advanced flap increased gingival thickness but did not improve root coverage versus flap alone at 1 year.

Trust comment: Assessor-blind randomized clinical trial with objective measures (n=24) but modest sample size.

Study Details

PMID:31292987
Participants:24
Impact:no difference between groups
Trust score:4/5

Lequesne Knee Index (function)

1 evidences

Intra-articular porcine-collagen product (MD-Knee) was non-inferior to sodium hyaluronate in improving function and pain in knee osteoarthritis up to 6 months.

Trust comment: Double-blind, randomized, active-controlled multicenter trial (64 enrolled, ~60 completers) with appropriate endpoints; no placebo arm and follow-up limited to 6 months.

Study Details

PMID:26905565
Participants:60
Impact:reduced in both groups; MD-Knee non-inferior to hyaluronate at 3 months
Trust score:4/5

painkiller consumption & SF-36

1 evidences

Intra-articular porcine-collagen product (MD-Knee) was non-inferior to sodium hyaluronate in improving function and pain in knee osteoarthritis up to 6 months.

Trust comment: Double-blind, randomized, active-controlled multicenter trial (64 enrolled, ~60 completers) with appropriate endpoints; no placebo arm and follow-up limited to 6 months.

Study Details

PMID:26905565
Participants:60
Impact:no significant difference between groups
Trust score:4/5

intraocular pressure (IOP)

4 evidences

In patients with open-angle glaucoma, very deep sclerectomy with a collagen implant provided good IOP control similar to standard deep sclerectomy over 2 years, with lower day-1 IOP in the very deep method.

Trust comment: Single-masked randomized controlled trial with adequate follow-up (mean ~19 months) though moderate sample size (48 patients).

Study Details

PMID:19373103
Participants:48
Impact:Day 1: VDSCI 3.9 mmHg vs DSCI 6.3 mmHg (−2.4 mmHg, p<0.05); 24 months: 12.2 vs 13.3 mmHg (NS)
Trust score:4/5

In a randomized multicenter trial, adding an Ologen collagen matrix to Ahmed valve surgery did not improve IOP control, medication need, hypertensive phase incidence, or 1-year success compared with standard surgery.

Trust comment: Randomized multicenter clinical trial in humans with clear outcomes, but relatively small sample and only 1-year follow-up limiting power for small differences.

Study Details

PMID:30816124
Participants:56
Impact:no significant difference at 12 months; higher IOP on day 1 in Ologen group (p=0.022)
Trust score:4/5

Collagen implants in deep sclerectomy produced intraocular pressure lowering and medication reduction comparable to a PMMA implant—no significant differences between implants.

Trust comment: Randomized controlled trial directly comparing collagen implant to alternative with mid-sized sample and extended follow-up; results robust for device comparison.

Study Details

PMID:16778652
Participants:60
Impact:21.0 mmHg baseline → 13.3 mmHg at 12 months (−7.7 mmHg)
Trust score:4/5

In phacotrabeculectomy, the collagen matrix implant and mitomycin C produced similar intraocular pressure lowering and success rates at 12 months.

Trust comment: Prospective randomized trial directly testing a collagen matrix implant with clear clinical endpoints; single-centre and nonblinded but well-reported.

Study Details

PMID:30924600
Participants:53
Impact:decreased from 26.4 to 13.7 mmHg (OLO) and 23.4 to 13.3 mmHg (MMC); no significant intergroup difference
Trust score:4/5

post-operative pain

2 evidences

In 64 patients, equine-derived collagenated xenogeneic bone blocks were non-inferior to autogenous bone blocks for horizontal ridge augmentation, with less early post-op pain.

Trust comment: Randomized non-inferiority clinical trial with objective radiographic endpoints and clinical outcomes; moderate sample size.

Study Details

PMID:35833539
Participants:64
Impact:reduced in CXBB group (significantly lower scores and analgesic use early post-op)
Trust score:4/5

Putting a collagen sponge into extraction sockets reduced pain after wisdom tooth surgery and may slightly lower dry-socket rates.

Trust comment: Split-mouth randomized controlled trial with objective outcomes in 31 patients; small sample limits precision.

Study Details

PMID:40316795
Participants:31
Impact:decreased on days 3 and 7 (statistically significant)
Trust score:4/5

mouth opening

1 evidences

Putting a collagen sponge into extraction sockets reduced pain after wisdom tooth surgery and may slightly lower dry-socket rates.

Trust comment: Split-mouth randomized controlled trial with objective outcomes in 31 patients; small sample limits precision.

Study Details

PMID:40316795
Participants:31
Impact:no significant change (minimally larger on collagen side)
Trust score:4/5

incidence of alveolar osteitis

1 evidences

Putting a collagen sponge into extraction sockets reduced pain after wisdom tooth surgery and may slightly lower dry-socket rates.

Trust comment: Split-mouth randomized controlled trial with objective outcomes in 31 patients; small sample limits precision.

Study Details

PMID:40316795
Participants:31
Impact:minimally decreased (not statistically significant)
Trust score:4/5

collagen type I

1 evidences

Daylight photodynamic therapy with pretreatment CO2 laser improved clinical and histologic outcomes for photodamaged facial skin, including a significant increase in collagen type I and reduced solar elastosis.

Trust comment: Randomized controlled study with histologic endpoints and paired biopsies, but modest sample size (four small arms) limits generalizability.

Study Details

PMID:34133958
Participants:40
Impact:Increased in DL‑PDT + CO2 laser group (p=0.028)
Trust score:4/5

osteocalcin (bone formation)

1 evidences

In postmenopausal breast cancer patients, tamoxifen reduced markers of bone resorption and formation and increased spine and femoral BMD, whereas toremifene showed smaller effects.

Trust comment: Randomized comparison with biochemical and BMD endpoints in 30 patients; moderate size but measured biomarkers and BMD are standard outcomes.

Study Details

PMID:9543133
Participants:30
Impact:tamoxifen decreased osteocalcin by ~25%
Trust score:4/5

Investigator Global Evaluation (efficacy of human collagen)

1 evidences

Human collagen injections produced rapid improvement in nasolabial folds but the effect mostly disappeared by 13 months; PLLA showed longer-lasting improvement.

Trust comment: Randomized multicenter trial with substantial sample size (n=233) and long follow-up; robust comparative design though not placebo-controlled.

Study Details

PMID:21719865
Participants:233
Impact:94% improved at 3 weeks; declined to 6% at 13 months
Trust score:4/5

safety profile

1 evidences

Human collagen injections produced rapid improvement in nasolabial folds but the effect mostly disappeared by 13 months; PLLA showed longer-lasting improvement.

Trust comment: Randomized multicenter trial with substantial sample size (n=233) and long follow-up; robust comparative design though not placebo-controlled.

Study Details

PMID:21719865
Participants:233
Impact:similar adverse event profile to PLLA
Trust score:4/5

cartilage repair quality (ICRS II score)

1 evidences

Adding collagen augmentation to microfracture improved biopsy-based cartilage repair quality at 1 year but clinical pain/function scores did not differ.

Trust comment: Randomized controlled trial with histologic and imaging endpoints (small sample, 1-year follow-up), methodology is appropriate but sample size limits generalizability.

Study Details

PMID:28282221
Participants:28
Impact:+167.8 points (+18.9%)
Trust score:4/5

tissue morphology / histologic features (MOCART/ICRS subscores)

1 evidences

Adding collagen augmentation to microfracture improved biopsy-based cartilage repair quality at 1 year but clinical pain/function scores did not differ.

Trust comment: Randomized controlled trial with histologic and imaging endpoints (small sample, 1-year follow-up), methodology is appropriate but sample size limits generalizability.

Study Details

PMID:28282221
Participants:28
Impact:improved (significant in multiple histologic subscores)
Trust score:4/5

clinical pain/function (VAS, KOOS, IKDC, Tegner)

1 evidences

Adding collagen augmentation to microfracture improved biopsy-based cartilage repair quality at 1 year but clinical pain/function scores did not differ.

Trust comment: Randomized controlled trial with histologic and imaging endpoints (small sample, 1-year follow-up), methodology is appropriate but sample size limits generalizability.

Study Details

PMID:28282221
Participants:28
Impact:no significant change at 1 year
Trust score:4/5

stratum corneum hydration

2 evidences

In older inpatients, daily oral supplement with 10 g collagen peptides for 8 weeks increased forearm skin hydration and elasticity versus control.

Trust comment: Randomized controlled trial with objective blinded measurements but open-label design and small sample (39 analyzed) limits strength.

Study Details

PMID:32195722
Participants:39
Impact:+8.0 units (+18.3%) (from 43.7 to 51.7 in intervention)
Trust score:4/5

Two single-center 28-day topical lotion studies (5% and 20% TBFE) in adults showed improved skin tone, reduced water loss, increased hydration and reduced wrinkles.

Trust comment: Human data from two small, single-center open pre–post studies (n=60 total) with objective measures but limited power and no placebo control.

Study Details

PMID:39161108
Participants:60
Impact:+~27% (5% lotion) and +~35% (20% lotion) at Day 28
Trust score:3/5

bone volumetric loss (augmented bone)

1 evidences

Resorbable collagen membrane produced similar augmented bone volumetric loss as platelet-rich fibrin at 6 months.

Trust comment: Randomized controlled clinical trial with objective CBCT measures but small sample (n=27) limiting power.

Study Details

PMID:30715758
Participants:27
Impact:control (resorbable collagen) 17.8% vs test (PRF) 14.7% (difference not significant, p=0.48)
Trust score:3/5

regional bone resorption (incisor/canine vs premolar)

1 evidences

Resorbable collagen membrane produced similar augmented bone volumetric loss as platelet-rich fibrin at 6 months.

Trust comment: Randomized controlled clinical trial with objective CBCT measures but small sample (n=27) limiting power.

Study Details

PMID:30715758
Participants:27
Impact:incisor/canine 23.41% vs premolar 11.89% (greater resorption in incisor/canine, p=0.01)
Trust score:3/5

time to pulmonary air leak closure

1 evidences

Compared polyglycolic acid (Neoveil) versus collagen sponge (TachoSil); Neoveil showed faster median air-leak closure and lower early air-loss AUC and lower PAL incidence, but differences were not statistically significant.

Trust comment: Prospective randomized trial with objective digital measurements and ITT analysis but single-center and underpowered for conclusive differences.

Study Details

PMID:36651370
Participants:45
Impact:median Neoveil 10 h vs TachoSil 19 h (median diff −9 h; p=0.35, not significant)
Trust score:4/5

24-h air leak AUC

1 evidences

Compared polyglycolic acid (Neoveil) versus collagen sponge (TachoSil); Neoveil showed faster median air-leak closure and lower early air-loss AUC and lower PAL incidence, but differences were not statistically significant.

Trust comment: Prospective randomized trial with objective digital measurements and ITT analysis but single-center and underpowered for conclusive differences.

Study Details

PMID:36651370
Participants:45
Impact:median Neoveil 668 ml/24h vs TachoSil 1894 ml/24h (median diff −1226 ml/24h; p=0.45, not significant)
Trust score:4/5

prolonged air leak (PAL) incidence

1 evidences

Compared polyglycolic acid (Neoveil) versus collagen sponge (TachoSil); Neoveil showed faster median air-leak closure and lower early air-loss AUC and lower PAL incidence, but differences were not statistically significant.

Trust comment: Prospective randomized trial with objective digital measurements and ITT analysis but single-center and underpowered for conclusive differences.

Study Details

PMID:36651370
Participants:45
Impact:Neoveil 14% (3/22) vs TachoSil 26% (6/23) (p=0.50, not significant)
Trust score:4/5

postoperative swelling (week 1)

1 evidences

At 6 months there were no statistically significant differences in functional and symptomatic outcomes between autologous cartilage and bovine/porcine acellular dermal matrix spacer grafts.

Trust comment: Prospective randomized clinical trial but small sample size and limited power to detect modest differences.

Study Details

PMID:28658181
Participants:32
Impact:higher with auricular cartilage vs bovine vs porcine (p=0.04)
Trust score:3/5

margin reflex distance 2 (MRD2) at 6 months

1 evidences

At 6 months there were no statistically significant differences in functional and symptomatic outcomes between autologous cartilage and bovine/porcine acellular dermal matrix spacer grafts.

Trust comment: Prospective randomized clinical trial but small sample size and limited power to detect modest differences.

Study Details

PMID:28658181
Participants:32
Impact:no statistically significant difference among groups after multiple comparison adjustment (trend favoring auricular cartilage, p=0.088 after adjustment)
Trust score:3/5

BMI

1 evidences

Eight-week double-blind RCT: hydrolysed collagen supplementation did not reduce android fat or increase nesfatin; the collagen group had a small BMI increase while whey reduced android fat and increased nesfatin.

Trust comment: Randomized double-blind trial with objective DXA measures but modest sample size and short duration (8 weeks).

Study Details

PMID:31480676
Participants:37
Impact:collagen group +0.2 kg/m^2 vs baseline (p=0.044, within-group increase)
Trust score:4/5

android fat

1 evidences

Eight-week double-blind RCT: hydrolysed collagen supplementation did not reduce android fat or increase nesfatin; the collagen group had a small BMI increase while whey reduced android fat and increased nesfatin.

Trust comment: Randomized double-blind trial with objective DXA measures but modest sample size and short duration (8 weeks).

Study Details

PMID:31480676
Participants:37
Impact:no decrease in collagen group (whey group decreased −0.1 kg, p=0.031 between groups)
Trust score:4/5

nesfatin (blood concentration)

1 evidences

Eight-week double-blind RCT: hydrolysed collagen supplementation did not reduce android fat or increase nesfatin; the collagen group had a small BMI increase while whey reduced android fat and increased nesfatin.

Trust comment: Randomized double-blind trial with objective DXA measures but modest sample size and short duration (8 weeks).

Study Details

PMID:31480676
Participants:37
Impact:no increase in collagen group (whey increased nesfatin by 4.9 ng/mL vs collagen, p=0.014)
Trust score:4/5

pigmentation (normal at 24 months)

1 evidences

Apligraf (a collagen-containing living skin substitute) applied over meshed autografts improved long-term cosmetic and functional wound outcomes versus control.

Trust comment: Randomized, within-patient controlled multicenter trial with long follow-up and clinically relevant outcomes; moderate sample and 38 evaluable.

Study Details

PMID:10925183
Participants:38
Impact:improved (45% Apligraf vs 13% control)
Trust score:4/5

vascularity (normal at 24 months)

1 evidences

Apligraf (a collagen-containing living skin substitute) applied over meshed autografts improved long-term cosmetic and functional wound outcomes versus control.

Trust comment: Randomized, within-patient controlled multicenter trial with long follow-up and clinically relevant outcomes; moderate sample and 38 evaluable.

Study Details

PMID:10925183
Participants:38
Impact:improved (47% Apligraf vs 16% control)
Trust score:4/5

Vancouver burn scar score

1 evidences

Apligraf (a collagen-containing living skin substitute) applied over meshed autografts improved long-term cosmetic and functional wound outcomes versus control.

Trust comment: Randomized, within-patient controlled multicenter trial with long follow-up and clinically relevant outcomes; moderate sample and 38 evaluable.

Study Details

PMID:10925183
Participants:38
Impact:improved (Apligraf sites better than control at all time points)
Trust score:4/5

fat mass (FM)

1 evidences

Twelve weeks of resistance training plus 15 g/day specific collagen peptides increased fat-free mass, reduced fat mass, and improved hand-grip strength more than placebo.

Trust comment: Double-blind, placebo-controlled randomized trial with adequate sample, supervised training, and consistent PP/ITT results; high internal validity.

Study Details

PMID:31010031
Participants:77
Impact:−1.5 ± 1.7 kg (TG) vs −0.7 ± 1.6 kg (CG)
Trust score:5/5

hand grip strength

1 evidences

Twelve weeks of resistance training plus 15 g/day specific collagen peptides increased fat-free mass, reduced fat mass, and improved hand-grip strength more than placebo.

Trust comment: Double-blind, placebo-controlled randomized trial with adequate sample, supervised training, and consistent PP/ITT results; high internal validity.

Study Details

PMID:31010031
Participants:77
Impact:+2.7 kg (TG) vs +1.3 kg (CG)
Trust score:5/5

collagen-induced platelet aggregation

4 evidences

Daily willow bark (salicin) modestly reduced platelet aggregation compared with placebo but far less than aspirin; no effect on collagen-induced aggregation.

Trust comment: Randomized double-blind but small groups and limited clinical outcome linkage; laboratory aggregation endpoints are clear.

Study Details

PMID:11345689
Participants:51
Impact:no significant change
Trust score:3/5

In healthy men, single IV doses of Revacept dose-dependently inhibited collagen-induced platelet aggregation without affecting bleeding time or general hemostasis.

Trust comment: Phase I first-in-human study with clear pharmacodynamic endpoints in 30 healthy volunteers, but small sample and early-phase design.

Study Details

PMID:21502572
Participants:30
Impact:dose-dependent inhibition (up to 48 h at low doses; up to 7 days at higher doses)
Trust score:3/5

Patterns of platelet inhibition differed by treatment; ER-DP+ASA caused later reductions in multiple platelet activation markers, while clopidogrel (with ASA) inhibited collagen-induced aggregation earlier.

Trust comment: Small, single-blind randomized trial using surrogate platelet biomarkers over 30 days; limited size and short duration.

Study Details

PMID:18343263
Participants:60
Impact:Addition of aspirin to clopidogrel associated with significant inhibition (P=0.001)
Trust score:3/5

In a double-blind crossover trial of elderly hypertensive patients, manidipine reduced thrombin/ADP- and collagen-induced platelet aggregation—particularly in those with type II diabetes—whereas atenolol did not.

Trust comment: Randomized double-blind crossover design in 60 patients gives credible clinical evidence though subgroup sizes are modest.

Study Details

PMID:15772518
Participants:60
Impact:decreased significantly with manidipine in diabetic patients; decreased only at highest inducer doses in nondiabetics; no change with atenolol
Trust score:4/5

hemostatic success within 10 minutes

2 evidences

A prospective controlled trial found a novel collagen-based hemostatic composite (CoStasis) achieved faster and more frequent rapid hemostasis than a collagen sponge after tumor resection.

Trust comment: Prospective controlled surgical trial with clear, large effect sizes though moderate sample and heterogeneous surgical sites.

Study Details

PMID:12356154
Participants:53
Impact:100% (CoStasis, 23/23) vs 70% (collagen sponge, 21/30)
Trust score:4/5

The collagen-based CoStasis hemostat produced higher hemostatic success and much faster bleeding control than standard manual compression across multiple surgical specialties.

Trust comment: Large randomized controlled trial with objective, clinically relevant endpoints and clear superiority signal.

Study Details

PMID:11283536
Participants:318
Impact:CoStasis 153/167 (>90%) vs control 88/151 (58%); superior with collagen-based composite
Trust score:5/5

time to complete hemostasis (median)

1 evidences

A prospective controlled trial found a novel collagen-based hemostatic composite (CoStasis) achieved faster and more frequent rapid hemostasis than a collagen sponge after tumor resection.

Trust comment: Prospective controlled surgical trial with clear, large effect sizes though moderate sample and heterogeneous surgical sites.

Study Details

PMID:12356154
Participants:53
Impact:78 s (CoStasis) vs 243 s (collagen sponge)
Trust score:4/5

residual biomaterial

1 evidences

In damaged tooth sockets grafted and covered with a collagen membrane, both bovine and porcine deproteinized bone produced similar amounts of new bone and residual material after 4 months.

Trust comment: Randomized controlled clinical trial with blinded participants and histologic endpoints, moderate sample for analyzed biopsies.

Study Details

PMID:31724239
Participants:81
Impact:DBBM 12.37% ±5.67 vs DPBM 12.21% ±5.75; no significant difference
Trust score:4/5

newly formed bone

2 evidences

Randomized clinical trial comparing flapped vs flapless socket grafting with porcine bone and collagen membrane found similar histological outcomes after 3 months.

Trust comment: Randomized clinical trial with quantitative histomorphometry (34 patients); reasonable quality for histologic endpoints.

Study Details

PMID:24580835
Participants:34
Impact:22.5% (no difference between groups)
Trust score:4/5

In damaged tooth sockets grafted and covered with a collagen membrane, both bovine and porcine deproteinized bone produced similar amounts of new bone and residual material after 4 months.

Trust comment: Randomized controlled clinical trial with blinded participants and histologic endpoints, moderate sample for analyzed biopsies.

Study Details

PMID:31724239
Participants:81
Impact:DBBM 15.07% ±10.52 vs DPBM 18.47% ±11.47; no significant difference
Trust score:4/5

nonmineralized tissue

1 evidences

In damaged tooth sockets grafted and covered with a collagen membrane, both bovine and porcine deproteinized bone produced similar amounts of new bone and residual material after 4 months.

Trust comment: Randomized controlled clinical trial with blinded participants and histologic endpoints, moderate sample for analyzed biopsies.

Study Details

PMID:31724239
Participants:81
Impact:DBBM 72.56% ±10.07 vs DPBM 71.55% ±15.47; no significant difference
Trust score:4/5

acne scar improvement

1 evidences

Adding PMMA-collagen gel injections after microneedling produced greater improvement in atrophic acne scars at 24 and 36 weeks compared with microneedling alone.

Trust comment: Multicenter randomized prospective study with objective outcomes, but open-label and moderate sample size.

Study Details

PMID:30807389
Participants:44
Impact:PMMA-collagen group showed statistically significant greater improvement at 24 weeks versus microneedling alone; improvement continued at 36 weeks
Trust score:4/5

bleb height

1 evidences

The biodegradable collagen implant (Ologen) provided similar long-term intraocular pressure control to mitomycin-C, with higher bleb height and no observed adverse reaction.

Trust comment: Randomized 24-month clinical trial with relevant clinical endpoints, though sample size is modest.

Study Details

PMID:21921953
Participants:40
Impact:Bleb height higher in Ologen group (P<0.05)
Trust score:4/5

vital bone percentage

2 evidences

Compared two xenograft ridge-preservation protocols in humans; the protocol using a cross-linked bovine collagen sponge produced more vital bone than the other, while clinical dimensional changes were similar.

Trust comment: Randomized controlled trial with histologic endpoints in 44 patients; moderate sample and clear results support moderate-high trust.

Study Details

PMID:22680300
Participants:44
Impact:+14.20 percentage points (47.03% vs 32.83%)
Trust score:4/5

Pilot RCT (27 patients) comparing PRF membrane vs standard graft coverage with deproteinized bovine bone and a resorbable collagen membrane; both showed similarly low bone vitality at 6 months.

Trust comment: Randomized pilot trial with objective histologic outcomes but small sample and limited power.

Study Details

PMID:32339370
Participants:27
Impact:14% (both groups; no significant difference, p>0.05)
Trust score:3/5

non-vital bone percentage

1 evidences

Pilot RCT (27 patients) comparing PRF membrane vs standard graft coverage with deproteinized bovine bone and a resorbable collagen membrane; both showed similarly low bone vitality at 6 months.

Trust comment: Randomized pilot trial with objective histologic outcomes but small sample and limited power.

Study Details

PMID:32339370
Participants:27
Impact:Test 80% vs Control 63% (no significant difference, p>0.05)
Trust score:3/5

plaque accumulation / inflammation grade

1 evidences

Randomized trial (30 participants) showing argon plasma-treated abutments reduced plaque/inflammation and increased connective tissue healing and collagen content at 2 months.

Trust comment: Small randomized clinical trial with histological endpoints and statistically significant differences; limited sample size but direct human data.

Study Details

PMID:37853303
Participants:30
Impact:PT 6.71% vs NPT 13.25% (−6.54 percentage points; p=0.02)
Trust score:4/5

connective tissue healing / collagen content

1 evidences

Randomized trial (30 participants) showing argon plasma-treated abutments reduced plaque/inflammation and increased connective tissue healing and collagen content at 2 months.

Trust comment: Small randomized clinical trial with histological endpoints and statistically significant differences; limited sample size but direct human data.

Study Details

PMID:37853303
Participants:30
Impact:PT 31.77% vs NPT 23.30% (+8.47 percentage points; p=0.009)
Trust score:4/5

uncorrected/corrected distance visual acuity

2 evidences

Prospective comparative clinical study comparing two accelerated corneal collagen cross-linking radiances (5.4 vs 7.2 J/cm2) showing similar visual and topographic outcomes at 12 months.

Trust comment: Prospective comparative study with moderate sample size; clinical outcomes objective but not randomized between doses.

Study Details

PMID:28358253
Participants:82
Impact:No significant difference between 5.4 and 7.2 J/cm2 protocols at 12 months
Trust score:3/5

In 50 patients with bilateral progressive keratoconus, continuous and pulsed accelerated corneal collagen cross-linking with supplemental oxygen produced comparable improvements in corneal topography and biomechanics at one year.

Trust comment: Prospective randomized paired-eye study with 12-month follow-up and objective measures, though right/left-eye allocation and single-center design limit generalizability.

Study Details

PMID:38162570
Participants:50
Impact:Mean improvements (UDVA ~0.11–0.18 logMAR; CDVA gain ~1 Snellen line) but not statistically significant
Trust score:4/5

corneal topography / keratometry

1 evidences

Prospective comparative clinical study comparing two accelerated corneal collagen cross-linking radiances (5.4 vs 7.2 J/cm2) showing similar visual and topographic outcomes at 12 months.

Trust comment: Prospective comparative study with moderate sample size; clinical outcomes objective but not randomized between doses.

Study Details

PMID:28358253
Participants:82
Impact:No significant difference between protocols (K readings and refractive results)
Trust score:3/5

serum osteocalcin

1 evidences

Postmenopausal women received varying doses of ibandronate; higher doses increased BMD and reduced biochemical markers of bone turnover including type I collagen breakdown products.

Trust comment: Randomized, double-blind controlled trial with clear biochemical and BMD endpoints, though multi-dose design complicates single-dose interpretation.

Study Details

PMID:8922653
Participants:141
Impact:decreased (−35% at 5.0 mg)
Trust score:4/5

sternal wound infection incidence

2 evidences

Large randomized trial: adding collagen-gentamicin sponges during sternotomy closure halved sternal wound infection rates.

Trust comment: Large randomized controlled trial with clear significant reduction in infections using collagen-based antibiotic sponges.

Study Details

PMID:17931240
Participants:2000
Impact:4.3% (collagen-gentamicin) vs 9.0% (control); RR=0.47, P<0.001
Trust score:5/5

In cardiac surgery patients, adding collagen–gentamicin sponges to standard prophylaxis halved sternal wound infection rates (4.3% vs 9.0%) but increased early reoperation for bleeding.

Trust comment: Large randomized double-blind trial using collagen-based local sponge as antibiotic carrier with clear reduction in infections but increased bleeding risk.

Study Details

PMID:15620935
Participants:1950
Impact:Reduced from 9.0% (control) to 4.3% (collagen–gentamicin sponge); relative risk 0.47 (95% CI 0.33–0.68); p < 0.001
Trust score:4/5

SWI due to coagulase-negative staphylococci (CoNS)

1 evidences

Large randomized trial: adding collagen-gentamicin sponges during sternotomy closure halved sternal wound infection rates.

Trust comment: Large randomized controlled trial with clear significant reduction in infections using collagen-based antibiotic sponges.

Study Details

PMID:17931240
Participants:2000
Impact:reduced incidence in treatment group (reported across major pathogens)
Trust score:5/5

complete wound closure (12 weeks)

1 evidences

Multicenter RCT found Promogran (collagen/ORC) produced numerically more healed diabetic foot ulcers overall and in recent ulcers, but primary outcome was not statistically significant.

Trust comment: Well-designed multicenter randomized trial using a collagen-containing dressing; primary outcome not statistically significant, sample adequate.

Study Details

PMID:12093340
Participants:276
Impact:37.0% Promogran vs 28.3% control (difference +8.7 percentage points; P=0.12)
Trust score:4/5

complete wound closure (<6 months wound duration)

1 evidences

Multicenter RCT found Promogran (collagen/ORC) produced numerically more healed diabetic foot ulcers overall and in recent ulcers, but primary outcome was not statistically significant.

Trust comment: Well-designed multicenter randomized trial using a collagen-containing dressing; primary outcome not statistically significant, sample adequate.

Study Details

PMID:12093340
Participants:276
Impact:45% Promogran vs 33% control (difference +12 percentage points; P=0.056; borderline)
Trust score:4/5

vertical bone resorption

1 evidences

Randomised trial comparing ARP techniques found that groups using bone graft plus collagen sponge or free gingival graft had less vertical and horizontal bone resorption than graftless treatment after 4 months.

Trust comment: Randomised study with 41 patients and clinically relevant comparisons involving collagen sponge, but limited sample size and short follow-up (4 months).

Study Details

PMID:37227497
Participants:41
Impact:decrease (groups A–C [graft + CS/FGG] showed significantly less vertical loss vs group D [FGG alone])
Trust score:3/5

horizontal bone resorption

2 evidences

Randomised trial comparing ARP techniques found that groups using bone graft plus collagen sponge or free gingival graft had less vertical and horizontal bone resorption than graftless treatment after 4 months.

Trust comment: Randomised study with 41 patients and clinically relevant comparisons involving collagen sponge, but limited sample size and short follow-up (4 months).

Study Details

PMID:37227497
Participants:41
Impact:decrease (groups A–C showed significantly less horizontal loss vs group D)
Trust score:3/5

Using a resorbable collagen membrane did not reduce horizontal bone resorption; piezosurgery showed no clinical advantage over rotative instruments and took longer.

Trust comment: Randomized split-mouth clinical trial in humans with clear outcome measures and moderate sample size.

Study Details

PMID:21745325
Participants:36
Impact:membrane 1.43 mm vs no membrane 1.06 mm (membrane +0.37 mm; p=0.062, NS)
Trust score:4/5

CTX (bone resorption marker)

3 evidences

Intermittent senolytic therapy did not reduce overall bone resorption but transiently increased a bone formation marker and showed benefit in a high-senescent-burden subgroup.

Trust comment: Phase 2 randomized controlled trial with clear endpoints and exploratory subgroup analyses; moderate sample size.

Study Details

PMID:38956196
Participants:60
Impact:D+Q -4.1% vs control -7.7% at 20 wk (no significant difference, P=0.611)
Trust score:4/5

Randomized double-blind trial in women >60: yogurt fortified with vitamin D3 (400 IU) and additional calcium increased 25OHD and decreased PTH and bone resorption markers over 12 weeks.

Trust comment: Randomized, double-blind design with good compliance and clear biochemical endpoints, though small completed sample size limits precision.

Study Details

PMID:25923487
Participants:48
Impact:change D84-D0: −0.085 μg/L (fortified) vs −0.024 μg/L (control; between-group difference not statistically significant)
Trust score:4/5

Randomized double-blind trial in thalassemia patients: weekly alendronate for 12 months increased lumbar (L1–L4) BMD and reduced bone turnover markers versus placebo.

Trust comment: Double-blind randomized controlled design with predefined endpoints and measured biomarkers; modest sample size but well-conducted.

Study Details

PMID:37251676
Participants:47
Impact:Decreased from 0.57 to 0.32 ng/ml (~-33.2%); p=0.002
Trust score:4/5

tendon thickness

1 evidences

Randomized double-blind trial comparing isolated bioinductive repair (implant that induces collagen deposition) versus sutured repair for small/medium full-thickness rotator cuff tears: bioinductive repair yielded superior collagen organization, greater tendon thickness increase, 100% MRI healing at 12/24 months, better PROs and faster return to work.

Trust comment: Well-conducted randomized, double-blind RCT with meaningful objective (biopsy, MRI) and patient-reported outcomes; single-center but adequate sample (n=60).

Study Details

PMID:38734130
Participants:60
Impact:greater increase (+2.0 mm IBR vs +0.8 mm control) at 6 months
Trust score:4/5

Cervical dentin hypersensitivity (CDH)

1 evidences

Randomized trial comparing coronally advanced flap with or without xenogenous collagen matrix and/or enamel matrix derivative for gingival recession; patients reported less dentin sensitivity and improved esthetics and oral-health quality of life after 6 months.

Trust comment: Randomized clinical trial directly testing a collagen matrix product with patient-reported outcomes; modest sample size and outcomes are subjective.

Study Details

PMID:28753098
Participants:68
Impact:decrease (statistically significant intragroup)
Trust score:4/5

Esthetic dissatisfaction

1 evidences

Randomized trial comparing coronally advanced flap with or without xenogenous collagen matrix and/or enamel matrix derivative for gingival recession; patients reported less dentin sensitivity and improved esthetics and oral-health quality of life after 6 months.

Trust comment: Randomized clinical trial directly testing a collagen matrix product with patient-reported outcomes; modest sample size and outcomes are subjective.

Study Details

PMID:28753098
Participants:68
Impact:decrease (statistically significant intragroup)
Trust score:4/5

Oral health-related quality of life (OHRQoL)

1 evidences

Randomized trial comparing coronally advanced flap with or without xenogenous collagen matrix and/or enamel matrix derivative for gingival recession; patients reported less dentin sensitivity and improved esthetics and oral-health quality of life after 6 months.

Trust comment: Randomized clinical trial directly testing a collagen matrix product with patient-reported outcomes; modest sample size and outcomes are subjective.

Study Details

PMID:28753098
Participants:68
Impact:improved (significant for CAF+CM, CAF+EMD, CAF+CM+EMD at 6 months)
Trust score:4/5

Manual compression time (hemostasis)

1 evidences

Randomized trial of percutaneous collagen plug implantation vs conventional haemostasis after coronary procedures showed dramatic reduction in manual compression time but increased access-site complications (notably after PTCA).

Trust comment: Randomized controlled trial directly testing collagen implants for hemostasis with clear objective outcomes, but increased complications limit safety interpretation.

Study Details

PMID:7588895
Participants:309
Impact:stenting: median 45 → 5 min; PTCA: 27 → 5 min (both P≤0.001)
Trust score:4/5

Access-site complications after PTCA

1 evidences

Randomized trial of percutaneous collagen plug implantation vs conventional haemostasis after coronary procedures showed dramatic reduction in manual compression time but increased access-site complications (notably after PTCA).

Trust comment: Randomized controlled trial directly testing collagen implants for hemostasis with clear objective outcomes, but increased complications limit safety interpretation.

Study Details

PMID:7588895
Participants:309
Impact:higher with collagen plugs: 16/117 vs 3/114 (P=0.0049)
Trust score:4/5

Access-site complications after stenting

1 evidences

Randomized trial of percutaneous collagen plug implantation vs conventional haemostasis after coronary procedures showed dramatic reduction in manual compression time but increased access-site complications (notably after PTCA).

Trust comment: Randomized controlled trial directly testing collagen implants for hemostasis with clear objective outcomes, but increased complications limit safety interpretation.

Study Details

PMID:7588895
Participants:309
Impact:no significant difference: 15/37 vs 17/41 (P=0.88)
Trust score:4/5

wound area

2 evidences

In patients with diabetic foot ulcers, local collagen dressings reduced wound area and depth more than standard care and similarly to NPWT.

Trust comment: Small controlled clinical comparison with clear reported percent changes but limited detail on randomization/blinding and sample size per arm is small (21 per group).

Study Details

PMID:29298017
Participants:63
Impact:-26.4% (collagen dressings group)
Trust score:3/5

In a small double‑blind RCT, multispectral LED treatment did not show overall superiority vs sham for grade‑2 sacral pressure ulcers; LED increased epidermal thickness and basement membrane measures but wound area changes were similar.

Trust comment: Double‑blind RCT with biopsies and objective measures but small sample, dropout, and baseline imbalances limit generalizability.

Study Details

PMID:39178286
Participants:27
Impact:Both groups showed significant pre‑to‑post reduction; no significant difference between LED and sham (p=0.061 overall)
Trust score:3/5

wound depth

1 evidences

In patients with diabetic foot ulcers, local collagen dressings reduced wound area and depth more than standard care and similarly to NPWT.

Trust comment: Small controlled clinical comparison with clear reported percent changes but limited detail on randomization/blinding and sample size per arm is small (21 per group).

Study Details

PMID:29298017
Participants:63
Impact:-30.4% (collagen dressings group)
Trust score:3/5

local tissue perfusion (oxygen monitoring)

1 evidences

In patients with diabetic foot ulcers, local collagen dressings reduced wound area and depth more than standard care and similarly to NPWT.

Trust comment: Small controlled clinical comparison with clear reported percent changes but limited detail on randomization/blinding and sample size per arm is small (21 per group).

Study Details

PMID:29298017
Participants:63
Impact:significant increase with NPWT; not reported as significant for collagen group
Trust score:3/5

KS function score (1-year)

1 evidences

Self-controlled randomized trial in bilateral TKA: adding mineralized (recombinant) collagen to PMMA cement was safe and produced a small short-term functional advantage (better KS function score at 1 year) but otherwise comparable outcomes to standard PMMA.

Trust comment: Prospective randomized self-controlled design with blinded assessor and mid-term follow-up, but small sample size limits power and long-term conclusions.

Study Details

PMID:40374827
Participants:32
Impact:+3.5 points (MC-PMMA 75.8 vs T-PMMA 72.3; p=0.0425)
Trust score:4/5

overall PROMs (HSS, KSS, WOMAC) at latest follow-up

1 evidences

Self-controlled randomized trial in bilateral TKA: adding mineralized (recombinant) collagen to PMMA cement was safe and produced a small short-term functional advantage (better KS function score at 1 year) but otherwise comparable outcomes to standard PMMA.

Trust comment: Prospective randomized self-controlled design with blinded assessor and mid-term follow-up, but small sample size limits power and long-term conclusions.

Study Details

PMID:40374827
Participants:32
Impact:no significant difference between MC-PMMA and T-PMMA
Trust score:4/5

radiolucent lines (RLL) incidence

1 evidences

Self-controlled randomized trial in bilateral TKA: adding mineralized (recombinant) collagen to PMMA cement was safe and produced a small short-term functional advantage (better KS function score at 1 year) but otherwise comparable outcomes to standard PMMA.

Trust comment: Prospective randomized self-controlled design with blinded assessor and mid-term follow-up, but small sample size limits power and long-term conclusions.

Study Details

PMID:40374827
Participants:32
Impact:12/32 (MC-PMMA) vs 16/32 (T-PMMA); difference not statistically significant (p=0.2980)
Trust score:4/5

PIIINP (collagen type III turnover marker) — association with echocardiographic response

1 evidences

Biomarker subanalysis in CRT recipients found that lower baseline PIIINP (a collagen turnover marker) predicted favorable echocardiographic response and lower long-term mortality/MACE risk.

Trust comment: Well-defined biomarker subanalysis with clinically relevant endpoints, but observational subanalysis design and modest sample size moderate overall confidence.

Study Details

PMID:26776557
Participants:74
Impact:low PIIINP associated with higher odds of response (OR 3.56; 95% CI 1.23–10.24; p=0.017)
Trust score:3/5

PIIINP — association with all-cause mortality and MACE

1 evidences

Biomarker subanalysis in CRT recipients found that lower baseline PIIINP (a collagen turnover marker) predicted favorable echocardiographic response and lower long-term mortality/MACE risk.

Trust comment: Well-defined biomarker subanalysis with clinically relevant endpoints, but observational subanalysis design and modest sample size moderate overall confidence.

Study Details

PMID:26776557
Participants:74
Impact:PIIINP predictive of mortality (OR 3.11; 95% CI 1.21–7.89; p=0.033) and major cardiac adverse events (OR 3.56; 95% CI 1.53–9.15; p=0.007)
Trust score:3/5

NT-proBNP — association with outcomes

1 evidences

Biomarker subanalysis in CRT recipients found that lower baseline PIIINP (a collagen turnover marker) predicted favorable echocardiographic response and lower long-term mortality/MACE risk.

Trust comment: Well-defined biomarker subanalysis with clinically relevant endpoints, but observational subanalysis design and modest sample size moderate overall confidence.

Study Details

PMID:26776557
Participants:74
Impact:NT-proBNP independently predicted mortality (OR 2.05; 95% CI 1.11–4.96; p=0.039) and MACE (OR 4.51; 95% CI 1.75–11.6; p=0.001)
Trust score:3/5

Facial type I collagen concentration

1 evidences

Topical estradiol or genistein applied to facial skin of postmenopausal women for 24 weeks increased type I and III collagen; estradiol produced a larger increase.

Trust comment: Randomized, double-blind controlled trial with biopsy-based collagen measurement but modest sample size (n=30).

Study Details

PMID:28508697
Participants:30
Impact:increase (statistically significant vs baseline)
Trust score:4/5

Facial type III collagen concentration

1 evidences

Topical estradiol or genistein applied to facial skin of postmenopausal women for 24 weeks increased type I and III collagen; estradiol produced a larger increase.

Trust comment: Randomized, double-blind controlled trial with biopsy-based collagen measurement but modest sample size (n=30).

Study Details

PMID:28508697
Participants:30
Impact:increase (statistically significant vs baseline)
Trust score:4/5

Estradiol versus genistein effect

1 evidences

Topical estradiol or genistein applied to facial skin of postmenopausal women for 24 weeks increased type I and III collagen; estradiol produced a larger increase.

Trust comment: Randomized, double-blind controlled trial with biopsy-based collagen measurement but modest sample size (n=30).

Study Details

PMID:28508697
Participants:30
Impact:estradiol produced greater increase (p<0.0001)
Trust score:4/5

Alveolar bone formation

1 evidences

In children undergoing secondary alveolar bone grafting, using a collagen membrane as an interpositional layer improved bone formation and density versus no membrane, similar to platelet-rich fibrin.

Trust comment: Randomized allocation and objective radiologic outcomes but small pediatric sample (36) and limited follow-up details reported here.

Study Details

PMID:38866686
Participants:36
Impact:increase (enhanced vs control)
Trust score:3/5

Alveolar bone density

1 evidences

In children undergoing secondary alveolar bone grafting, using a collagen membrane as an interpositional layer improved bone formation and density versus no membrane, similar to platelet-rich fibrin.

Trust comment: Randomized allocation and objective radiologic outcomes but small pediatric sample (36) and limited follow-up details reported here.

Study Details

PMID:38866686
Participants:36
Impact:increase (enhanced vs control)
Trust score:3/5

Corneal curvature (keratometry)

1 evidences

In patients with progressive bilateral keratoconus, corneal collagen cross-linking of one eye halted progression and in many eyes improved topography and vision over 18 months compared with the untreated fellow eye.

Trust comment: Randomized, masked bilateral (one-eye) design with 18-month follow-up but modest sample size (n=24) limits precision.

Study Details

PMID:21349938
Participants:24
Impact:decrease (significant vs untreated eye)
Trust score:4/5

Simulated astigmatism and topographic measures

1 evidences

In patients with progressive bilateral keratoconus, corneal collagen cross-linking of one eye halted progression and in many eyes improved topography and vision over 18 months compared with the untreated fellow eye.

Trust comment: Randomized, masked bilateral (one-eye) design with 18-month follow-up but modest sample size (n=24) limits precision.

Study Details

PMID:21349938
Participants:24
Impact:decrease (significant vs untreated eye)
Trust score:4/5

Best spectacle-corrected visual acuity

2 evidences

Corneal collagen cross-linking stabilized progressive keratoconus and reduced corneal steepness over 12 months.

Trust comment: Randomized controlled human trial with objective ophthalmic outcomes; interim analysis and moderate sample size.

Study Details

PMID:18811118
Participants:49
Impact:Trend toward improvement in treated eyes; control decreased by logMAR 0.12 at 12 mo
Trust score:4/5

In patients with progressive bilateral keratoconus, corneal collagen cross-linking of one eye halted progression and in many eyes improved topography and vision over 18 months compared with the untreated fellow eye.

Trust comment: Randomized, masked bilateral (one-eye) design with 18-month follow-up but modest sample size (n=24) limits precision.

Study Details

PMID:21349938
Participants:24
Impact:improvement (significant in treated eyes)
Trust score:4/5

dGEMRIC T1 – medial tibial cartilage

1 evidences

In this pilot RCT, collagen hydrolysate supplementation produced region-specific increases in dGEMRIC T1 (suggesting increased proteoglycan) in medial and lateral tibial cartilage at 24 weeks versus declines with placebo; no other MRI, clinical, or T2 changes were seen.

Trust comment: Pilot randomized, double-blind trial with objective MRI signal changes but small sample (n=30) and limited clinical correlation.

Study Details

PMID:21251991
Participants:30
Impact:median +29 ms (collagen) vs −37 ms (placebo) at 24 weeks
Trust score:3/5

dGEMRIC T1 – lateral tibial cartilage

1 evidences

In this pilot RCT, collagen hydrolysate supplementation produced region-specific increases in dGEMRIC T1 (suggesting increased proteoglycan) in medial and lateral tibial cartilage at 24 weeks versus declines with placebo; no other MRI, clinical, or T2 changes were seen.

Trust comment: Pilot randomized, double-blind trial with objective MRI signal changes but small sample (n=30) and limited clinical correlation.

Study Details

PMID:21251991
Participants:30
Impact:median +41 ms (collagen) vs −36 ms (placebo) at 24 weeks
Trust score:3/5

Clinical symptoms and T2 mapping

1 evidences

In this pilot RCT, collagen hydrolysate supplementation produced region-specific increases in dGEMRIC T1 (suggesting increased proteoglycan) in medial and lateral tibial cartilage at 24 weeks versus declines with placebo; no other MRI, clinical, or T2 changes were seen.

Trust comment: Pilot randomized, double-blind trial with objective MRI signal changes but small sample (n=30) and limited clinical correlation.

Study Details

PMID:21251991
Participants:30
Impact:no significant change
Trust score:3/5

Perioperative stroke rate (collagen-impregnated Dacron vs PTFE)

1 evidences

In randomized carotid endarterectomy, collagen-impregnated Dacron (Hemashield) patching was associated with higher perioperative stroke, thrombosis, and early restenosis rates compared with PTFE, but had shorter hemostasis time.

Trust comment: Large randomized perioperative trial (n=200 CEAs) with clear clinical endpoints though follow-up here is limited to early (30-day) outcomes.

Study Details

PMID:11802143
Participants:200
Impact:HP 7% vs PTFE 0% (increase)
Trust score:4/5

Combined perioperative stroke or TIA

1 evidences

In randomized carotid endarterectomy, collagen-impregnated Dacron (Hemashield) patching was associated with higher perioperative stroke, thrombosis, and early restenosis rates compared with PTFE, but had shorter hemostasis time.

Trust comment: Large randomized perioperative trial (n=200 CEAs) with clear clinical endpoints though follow-up here is limited to early (30-day) outcomes.

Study Details

PMID:11802143
Participants:200
Impact:HP 12% vs PTFE 3% (increase)
Trust score:4/5

Early restenosis ≥50% at 1 month

1 evidences

In randomized carotid endarterectomy, collagen-impregnated Dacron (Hemashield) patching was associated with higher perioperative stroke, thrombosis, and early restenosis rates compared with PTFE, but had shorter hemostasis time.

Trust comment: Large randomized perioperative trial (n=200 CEAs) with clear clinical endpoints though follow-up here is limited to early (30-day) outcomes.

Study Details

PMID:11802143
Participants:200
Impact:HP 12% vs PTFE 2% (increase)
Trust score:4/5

drainage volume

1 evidences

Use of a fibrinogen/coagulation-factor coated collagen patch (TachoSil) at lymphadenectomy sites was associated with lower drainage volume and fewer lymphoceles compared with historical controls.

Trust comment: Matched case-control with small sample and historical controls; suggests benefit but limited by non-randomized design.

Study Details

PMID:23574881
Participants:55
Impact:reduced in treatment group (numeric values not reported in text)
Trust score:3/5

transfusion rate

2 evidences

Collagen hemostatic sponge reduced postoperative bleeding, transfusions, and hospital stay versus gelatin sponge; topical TXA reduced bleeding more than collagen.

Trust comment: Prospective randomized controlled trial with 120 patients and objective measured outcomes; moderate quality.

Study Details

PMID:29110696
Participants:120
Impact:3/40 (7.5%) vs 12/40 (30%) (−22.5 percentage points)
Trust score:4/5

Double‑blind RCT testing a topical collagen/thrombin/autologous platelet haemostatic agent in primary cementless THA to reduce transfusions and blood loss.

Trust comment: Well‑designed double‑blind randomized trial but modest size and limited to relatively healthy primary THA patients.

Study Details

PMID:26057484
Participants:109
Impact:8.3% (treatment) vs 14.3% (control), p=0.33 (no significant difference)
Trust score:4/5

postoperative hemoglobin

1 evidences

Double‑blind RCT testing a topical collagen/thrombin/autologous platelet haemostatic agent in primary cementless THA to reduce transfusions and blood loss.

Trust comment: Well‑designed double‑blind randomized trial but modest size and limited to relatively healthy primary THA patients.

Study Details

PMID:26057484
Participants:109
Impact:higher in treatment group on postoperative days 1–3 (p=0.002, 0.04, 0.02 respectively)
Trust score:4/5

buccal keratinized tissue width

1 evidences

Randomized trial comparing ridge preservation with non‑crosslinked collagen membrane (submerged) versus crosslinked collagen membrane left exposed plus allograft; assessed soft and hard tissue dimensional outcomes at 6 months.

Trust comment: Randomized controlled clinical trial with objective measurements but limited sample size (pilot scale) and short follow‑up (6 months).

Study Details

PMID:30367733
Participants:28
Impact:+0.43 ± 0.42 mm (crosslinked exposed) vs −1.57 ± 0.51 mm (non‑crosslinked submerged), P = 0.006
Trust score:4/5

buccal tissue thickness

1 evidences

Randomized trial comparing ridge preservation with non‑crosslinked collagen membrane (submerged) versus crosslinked collagen membrane left exposed plus allograft; assessed soft and hard tissue dimensional outcomes at 6 months.

Trust comment: Randomized controlled clinical trial with objective measurements but limited sample size (pilot scale) and short follow‑up (6 months).

Study Details

PMID:30367733
Participants:28
Impact:+0.46 ± 0.22 mm (crosslinked exposed) vs −0.15 ± 0.23 mm (control), P = 0.068
Trust score:4/5

crestal width reduction

1 evidences

Randomized trial comparing ridge preservation with non‑crosslinked collagen membrane (submerged) versus crosslinked collagen membrane left exposed plus allograft; assessed soft and hard tissue dimensional outcomes at 6 months.

Trust comment: Randomized controlled clinical trial with objective measurements but limited sample size (pilot scale) and short follow‑up (6 months).

Study Details

PMID:30367733
Participants:28
Impact:reduction 1.74 ± 0.40 mm (crosslinked exposed) vs 4.18 ± 0.56 mm (control), P = 0.003
Trust score:4/5

skin elasticity (neck)

1 evidences

Small randomized double‑blind placebo‑controlled trial of an oral fish‑derived collagen peptide plus ornithine drink given nightly for 8 weeks in adults with low skin moisture/elasticity, measuring skin elasticity, TEWL, pores, and IGF‑1.

Trust comment: Randomized double‑blind design is strong, but very small sample size and combined collagen+ornithine formulation limit generalizability and attribution to collagen alone.

Study Details

PMID:30513923
Participants:21
Impact:change from baseline +0.018 ± 0.065 (CPO) vs −0.039 ± 0.047 (placebo); between‑group difference significant
Trust score:3/5

plasma IGF‑1

1 evidences

Small randomized double‑blind placebo‑controlled trial of an oral fish‑derived collagen peptide plus ornithine drink given nightly for 8 weeks in adults with low skin moisture/elasticity, measuring skin elasticity, TEWL, pores, and IGF‑1.

Trust comment: Randomized double‑blind design is strong, but very small sample size and combined collagen+ornithine formulation limit generalizability and attribution to collagen alone.

Study Details

PMID:30513923
Participants:21
Impact:increase from baseline in CPO group (intra‑group significant); between‑group difference not significant
Trust score:3/5

injection volume required

1 evidences

Bovine collagen injections provided temporary wrinkle correction but were less durable and required more volume than hyaluronic acid; side-effect profiles were similar.

Trust comment: Randomized, double-blind multicenter trial with 138 patients and blinded assessments supports moderate-high reliability for comparative effectiveness of bovine collagen as a filler.

Study Details

PMID:12786700
Participants:138
Impact:greater volume required than hyaluronic acid
Trust score:4/5

duration of clinical benefit

1 evidences

Higher baseline serum NTx (a bone collagen breakdown marker) was associated with shorter clinical benefit duration, shorter time to progression, and shorter overall survival.

Trust comment: Large (n=250) clinical dataset with clear, statistically significant prognostic differences for a validated bone-collagen marker supports moderate-high trustworthiness.

Study Details

PMID:14998848
Participants:250
Impact:significantly shorter in patients with elevated NTx
Trust score:4/5

time to progression (TTP)

1 evidences

Higher baseline serum NTx (a bone collagen breakdown marker) was associated with shorter clinical benefit duration, shorter time to progression, and shorter overall survival.

Trust comment: Large (n=250) clinical dataset with clear, statistically significant prognostic differences for a validated bone-collagen marker supports moderate-high trustworthiness.

Study Details

PMID:14998848
Participants:250
Impact:shorter: 139 days vs 220 days (elevated vs normal NTx)
Trust score:4/5

overall survival

2 evidences

Higher baseline serum NTx (a bone collagen breakdown marker) was associated with shorter clinical benefit duration, shorter time to progression, and shorter overall survival.

Trust comment: Large (n=250) clinical dataset with clear, statistically significant prognostic differences for a validated bone-collagen marker supports moderate-high trustworthiness.

Study Details

PMID:14998848
Participants:250
Impact:shorter: 663 days vs 941 days (elevated vs normal NTx)
Trust score:4/5

Single‑center randomized trial: placing a gentamicin‑collagen implant in the pelvis at surgery was associated with a lower 5‑year cumulative incidence of distant metastases versus control.

Trust comment: Randomized long‑term follow‑up but single‑institution, modest sample and some unplanned subgroup analyses limit certainty.

Study Details

PMID:29656304
Participants:162
Impact:no significant difference (OS HR 0.95; P=0.864)
Trust score:3/5

analgesic consumption

1 evidences

Adding cyanoacrylate over a hemostatic collagen sponge on palatal donor sites reduced postoperative pain and analgesic use after graft harvesting.

Trust comment: Randomized clinical trial (n=44) showing significant patient-reported outcomes; moderate sample size limits precision but design is appropriate.

Study Details

PMID:29713890
Participants:44
Impact:decreased with cyanoacrylate over collagen sponge
Trust score:3/5

patient discomfort associated with graft width

1 evidences

Adding cyanoacrylate over a hemostatic collagen sponge on palatal donor sites reduced postoperative pain and analgesic use after graft harvesting.

Trust comment: Randomized clinical trial (n=44) showing significant patient-reported outcomes; moderate sample size limits precision but design is appropriate.

Study Details

PMID:29713890
Participants:44
Impact:less discomfort when graft width <14 mm
Trust score:3/5

ADP-induced platelet aggregation

2 evidences

Daily willow bark (salicin) modestly reduced platelet aggregation compared with placebo but far less than aspirin; no effect on collagen-induced aggregation.

Trust comment: Randomized double-blind but small groups and limited clinical outcome linkage; laboratory aggregation endpoints are clear.

Study Details

PMID:11345689
Participants:51
Impact:significant reduction vs placebo (p=0.01)
Trust score:3/5

Adding clopidogrel to aspirin significantly reduced multiple measures of platelet activation versus aspirin alone in heart failure patients with heightened platelet activity.

Trust comment: Randomized trial with clear between-group differences on multiple platelet function assays, though modest sample size.

Study Details

PMID:14564328
Participants:50
Impact:decreased (P = .00001)
Trust score:4/5

Spherical equivalent (SE)

2 evidences

Using donor corneas pretreated with corneal collagen cross-linking led to better visual acuity and less myopia/astigmatism after penetrating keratoplasty over 3 years.

Trust comment: Well-powered randomized controlled trial (n=116) with 3‑year follow-up showing consistent improvements in visual and topographic outcomes.

Study Details

PMID:29032110
Participants:116
Impact:Less myopic by 0.52 D (−3.50 ±2.93 D vs −4.02 ±2.57 D; P=0.034)
Trust score:4/5

Prospective randomized study comparing CXL protocols in 138 keratoconus patients found significant improvements in visual and refractive outcomes for several accelerated and conventional protocols at 12 months, with some protocols performing better than others.

Trust comment: Prospective randomized interventional study with 138 patients and 12-month follow-up; results reported with statistical significance though specific effect sizes are not provided in the abstract.

Study Details

PMID:26008626
Participants:138
Impact:Improved (statistically significant) in Groups I-II-III; not significant in Group IV
Trust score:4/5

Keratometry (flat/steep)

1 evidences

Prospective randomized study comparing CXL protocols in 138 keratoconus patients found significant improvements in visual and refractive outcomes for several accelerated and conventional protocols at 12 months, with some protocols performing better than others.

Trust comment: Prospective randomized interventional study with 138 patients and 12-month follow-up; results reported with statistical significance though specific effect sizes are not provided in the abstract.

Study Details

PMID:26008626
Participants:138
Impact:Significant flattening in Groups I and II compared to other groups
Trust score:4/5

Vertical defect fill

1 evidences

Multi-center analysis of 59 Class II furcation pairs found bioabsorbable collagen membrane improved vertical defect fill, percent defect resolution, and horizontal furcation fill versus debridement and performed similarly to ePTFE.

Trust comment: Multi-center clinical data with surgical re-entry (~11 months) and 59 defect pairs; favorable results though surgical studies are not blinded and outcomes are site-specific.

Study Details

PMID:8832475
Participants:59
Impact:Collagen membrane showed greater vertical defect fill compared to debridement
Trust score:4/5

Percent defect resolution

1 evidences

Multi-center analysis of 59 Class II furcation pairs found bioabsorbable collagen membrane improved vertical defect fill, percent defect resolution, and horizontal furcation fill versus debridement and performed similarly to ePTFE.

Trust comment: Multi-center clinical data with surgical re-entry (~11 months) and 59 defect pairs; favorable results though surgical studies are not blinded and outcomes are site-specific.

Study Details

PMID:8832475
Participants:59
Impact:Higher percent defect resolution with collagen membrane versus debridement; similar to ePTFE
Trust score:4/5

Complete furcation closures

1 evidences

Multi-center analysis of 59 Class II furcation pairs found bioabsorbable collagen membrane improved vertical defect fill, percent defect resolution, and horizontal furcation fill versus debridement and performed similarly to ePTFE.

Trust comment: Multi-center clinical data with surgical re-entry (~11 months) and 59 defect pairs; favorable results though surgical studies are not blinded and outcomes are site-specific.

Study Details

PMID:8832475
Participants:59
Impact:Collagen membrane yielded 8 clinically-complete closures vs 1 with ePTFE
Trust score:4/5

Tear trough deformity score

1 evidences

Randomized comparative study of 60 patients found that combining hyaluronic acid with collagen reduced the Tyndall effect and that differences in aesthetic/tear trough scores emerged by 3 months between groups.

Trust comment: Randomized single-center comparative study with 60 patients and 3-month follow-up; clinically relevant endpoints though follow-up is short and sample moderate.

Study Details

PMID:38299745
Participants:60
Impact:No group differences at 1 month; significant difference at 3 months between Group C (collagen alone) and Groups A/B (p significant)
Trust score:4/5

Global aesthetic improvement score

1 evidences

Randomized comparative study of 60 patients found that combining hyaluronic acid with collagen reduced the Tyndall effect and that differences in aesthetic/tear trough scores emerged by 3 months between groups.

Trust comment: Randomized single-center comparative study with 60 patients and 3-month follow-up; clinically relevant endpoints though follow-up is short and sample moderate.

Study Details

PMID:38299745
Participants:60
Impact:No difference at 1 month; differences apparent at 3 months (significant) between collagen-only and other groups
Trust score:4/5

Tyndall effect occurrence

1 evidences

Randomized comparative study of 60 patients found that combining hyaluronic acid with collagen reduced the Tyndall effect and that differences in aesthetic/tear trough scores emerged by 3 months between groups.

Trust comment: Randomized single-center comparative study with 60 patients and 3-month follow-up; clinically relevant endpoints though follow-up is short and sample moderate.

Study Details

PMID:38299745
Participants:60
Impact:Occurred in 3 patients in hyaluronic acid alone group (Group A); significantly fewer cases in combined or collagen-alone groups
Trust score:4/5

radiographic defect fill (RDF)

1 evidences

Adding a collagen membrane plus bone mineral resulted in more radiographic bone fill but no differences in clinical signs or patient-reported outcomes at 12 months.

Trust comment: Multicenter randomized clinical trial with objective radiographic and clinical endpoints but moderate sample size.

Study Details

PMID:34169551
Participants:66
Impact:TG 2.7 mm vs CG 1.4 mm (difference +1.3 mm; p < 0.0001)
Trust score:4/5

implant sites with new bone-like tissue

1 evidences

Filling extraction/implant defects with a hydroxyapatite–collagen material led to more implant sites covered by new bone-like tissue than leaving defects empty.

Trust comment: Clinical and histologic study with a moderate sample of treated defects but unclear randomization and participant-level details.

Study Details

PMID:12956481
Participants:96
Impact:67% (Biostite) vs 34% (no fill) — +33 percentage points
Trust score:3/5

histologic bone formation (endochondral osteogenesis)

1 evidences

Filling extraction/implant defects with a hydroxyapatite–collagen material led to more implant sites covered by new bone-like tissue than leaving defects empty.

Trust comment: Clinical and histologic study with a moderate sample of treated defects but unclear randomization and participant-level details.

Study Details

PMID:12956481
Participants:96
Impact:Observed in treated sites (qualitative histology)
Trust score:3/5

complete DFU closure at 16 weeks

1 evidences

A collagen-based dermal template increased complete wound closure rates and sped healing compared with standard care in chronic diabetic foot ulcers.

Trust comment: Large multicenter randomized controlled trial with clear endpoints and statistically significant effects.

Study Details

PMID:26297933
Participants:307
Impact:51% (IDRT) vs 32% (control); p = 0.001
Trust score:5/5

median time to complete closure

1 evidences

A collagen-based dermal template increased complete wound closure rates and sped healing compared with standard care in chronic diabetic foot ulcers.

Trust comment: Large multicenter randomized controlled trial with clear endpoints and statistically significant effects.

Study Details

PMID:26297933
Participants:307
Impact:43 days (IDRT) vs 78 days (control)
Trust score:5/5

wound size reduction rate

1 evidences

A collagen-based dermal template increased complete wound closure rates and sped healing compared with standard care in chronic diabetic foot ulcers.

Trust comment: Large multicenter randomized controlled trial with clear endpoints and statistically significant effects.

Study Details

PMID:26297933
Participants:307
Impact:7.2%/week (IDRT) vs 4.8%/week (control); p = 0.012
Trust score:5/5

urinary calcium excretion

2 evidences

Randomized feeding study: the DASH diet lowered bone turnover markers and sodium reduction decreased calcium excretion and some bone markers; vitamin D was discussed but not tested.

Trust comment: Large randomized feeding study with controlled diets and clear biomarker changes; shows dietary effects on collagen-derived bone turnover markers (high trust for biomarker outcomes).

Study Details

PMID:14519796
Participants:186
Impact:no difference between DASH and control diets; reduced with lower sodium
Trust score:4/5

12-week randomized dietary supplement trial in adults with abdominal obesity; whey protein increased urinary calcium but did not change bone turnover markers or BMD.

Trust comment: Randomized controlled intervention with objective biochemical measures and reasonable sample size, but post-hoc analysis and limited duration.

Study Details

PMID:35422766
Participants:64
Impact:increased in protein groups (significant)
Trust score:4/5

cure rate at 1 year

1 evidences

Post-hoc analysis of a multicenter randomized trial comparing a collagen gel versus hydrogel for urethral injection showed overall rates of cure/improvement at 1 year and identified patient factors linked to success.

Trust comment: Large multicenter randomized trial dataset; this is a post-hoc subgroup analysis but based on substantial sample size.

Study Details

PMID:30810462
Participants:291
Impact:74/291 (25%) cured
Trust score:4/5

improvement rate at 1 year

1 evidences

Post-hoc analysis of a multicenter randomized trial comparing a collagen gel versus hydrogel for urethral injection showed overall rates of cure/improvement at 1 year and identified patient factors linked to success.

Trust comment: Large multicenter randomized trial dataset; this is a post-hoc subgroup analysis but based on substantial sample size.

Study Details

PMID:30810462
Participants:291
Impact:164/291 (56%) improved (≥50% reduction in episodes)
Trust score:4/5

treatment success in older/less-severe subgroup

1 evidences

Post-hoc analysis of a multicenter randomized trial comparing a collagen gel versus hydrogel for urethral injection showed overall rates of cure/improvement at 1 year and identified patient factors linked to success.

Trust comment: Large multicenter randomized trial dataset; this is a post-hoc subgroup analysis but based on substantial sample size.

Study Details

PMID:30810462
Participants:291
Impact:women ≥60 yrs with <2.5 daily episodes: 90% had treatment effect, 38% cured
Trust score:4/5

ulcer dimension reduction

1 evidences

Randomized trial in diabetic foot ulcers compared oxidized regenerated cellulose/collagen dressing, autologous growth factors, and their combination over 8 weeks.

Trust comment: Prospective randomized clinical trial with clear endpoints and statistically significant results though modest sample size.

Study Details

PMID:17967712
Participants:51
Impact:combination (collagen matrix + growth factors) produced significantly greater reduction in all three ulcer dimensions vs either alone (p<.001)
Trust score:4/5

mineralized tissue proportion

1 evidences

Randomized clinical trial evaluated histologic and imaging outcomes at 3, 6, and 9 months after socket preservation with deproteinized bovine bone mineral with collagen and a porcine collagen matrix.

Trust comment: Well-designed randomized clinical trial with histomorphometric and imaging outcomes, limited by moderate sample size and site selection.

Study Details

PMID:36345818
Participants:42
Impact:increased with time: 13.53% (3 mo), 33.33% (6 mo), 37.05% (9 mo)
Trust score:4/5

remaining xenograft material

1 evidences

Randomized clinical trial evaluated histologic and imaging outcomes at 3, 6, and 9 months after socket preservation with deproteinized bovine bone mineral with collagen and a porcine collagen matrix.

Trust comment: Well-designed randomized clinical trial with histomorphometric and imaging outcomes, limited by moderate sample size and site selection.

Study Details

PMID:36345818
Participants:42
Impact:decreased with time: 16.94% (3 mo), 10.69% (6 mo), 9.46% (9 mo); similar between 6 and 9 mo
Trust score:4/5

total alveolar bone volume change

1 evidences

Randomized clinical trial evaluated histologic and imaging outcomes at 3, 6, and 9 months after socket preservation with deproteinized bovine bone mineral with collagen and a porcine collagen matrix.

Trust comment: Well-designed randomized clinical trial with histomorphometric and imaging outcomes, limited by moderate sample size and site selection.

Study Details

PMID:36345818
Participants:42
Impact:median changes: −6.36% (3 mo), −7.94% (6 mo), −12.45% (9 mo); progressive volumetric resorption
Trust score:4/5

Soft tissue height

1 evidences

Adding deproteinized bovine bone with collagen during immediate dental implant placement improved soft tissue height and buccolingual ridge width vs implant alone.

Trust comment: Randomized clinical trial but small sample (n=22); shows clinically significant soft- and hard-tissue improvements with collagen-containing graft material.

Study Details

PMID:30693399
Participants:22
Impact:Increased height at mesiobuccal and distobuccal sites at 3 and 6 months (p<0.05)
Trust score:3/5

Buccolingual ridge dimension (bone)

1 evidences

Adding deproteinized bovine bone with collagen during immediate dental implant placement improved soft tissue height and buccolingual ridge width vs implant alone.

Trust comment: Randomized clinical trial but small sample (n=22); shows clinically significant soft- and hard-tissue improvements with collagen-containing graft material.

Study Details

PMID:30693399
Participants:22
Impact:Increased buccolingual ridge width at 6 months (p<0.05)
Trust score:3/5

Keratometrical astigmatism (topographic)

1 evidences

Using donor corneas pretreated with corneal collagen cross-linking led to better visual acuity and less myopia/astigmatism after penetrating keratoplasty over 3 years.

Trust comment: Well-powered randomized controlled trial (n=116) with 3‑year follow-up showing consistent improvements in visual and topographic outcomes.

Study Details

PMID:29032110
Participants:116
Impact:Reduced by 1.45 D (4.53 ±1.06 D vs 5.98 ±1.28 D; P<0.001)
Trust score:4/5

Hypertensive phase frequency

1 evidences

Placing an Ologen collagen matrix with Ahmed glaucoma valve implantation lowered early postoperative IOP and reduced the hypertensive phase frequency but did not change long-term success rates.

Trust comment: Randomized controlled trial but small sample (n=26); shows intermediate-term IOP benefits with Ologen collagen matrix but limited power for long-term outcomes.

Study Details

PMID:33338679
Participants:26
Impact:Reduced frequency in Ologen group (38.5%) vs control (61.5%)
Trust score:3/5

bleeding score

1 evidences

Compared a synthetic bone sealant to a collagen fleece for stopping bleeding after iliac crest bone harvesting; both were safe and had similar wound-healing.

Trust comment: Prospective randomized multicenter study with objective scores, but open-label and limited detail on clinical impact.

Study Details

PMID:16135979
Participants:112
Impact:collagen fleece mean 4.2 vs Bone Seal 4.5 (difference −0.3 points)
Trust score:3/5

wound healing score

1 evidences

Compared a synthetic bone sealant to a collagen fleece for stopping bleeding after iliac crest bone harvesting; both were safe and had similar wound-healing.

Trust comment: Prospective randomized multicenter study with objective scores, but open-label and limited detail on clinical impact.

Study Details

PMID:16135979
Participants:112
Impact:comparable between collagen fleece and Bone Seal (no meaningful difference)
Trust score:3/5

adverse event incidence

2 evidences

Compared a synthetic bone sealant to a collagen fleece for stopping bleeding after iliac crest bone harvesting; both were safe and had similar wound-healing.

Trust comment: Prospective randomized multicenter study with objective scores, but open-label and limited detail on clinical impact.

Study Details

PMID:16135979
Participants:112
Impact:comparable between groups (no meaningful difference)
Trust score:3/5

Randomized trial in patients with bone defects: porous hydroxyapatite/collagen implant produced superior radiographic bone regeneration versus porous β-TCP by 18–24 weeks, with more (non-serious) adverse events.

Trust comment: Randomized controlled trial with objective radiographic endpoints and 119 analyzed patients; clear primary outcome reporting.

Study Details

PMID:26961287
Participants:119
Impact:Higher incidence in HAp/Col group vs β-TCP, but no serious adverse events reported
Trust score:4/5

SNOT-25 symptom score

1 evidences

Compared acellular dermal graft (collagen-containing) to silastic implants for empty nose syndrome; both groups showed marked symptom improvement.

Trust comment: Small randomized blinded study with subjective outcomes showing benefit, but limited sample size.

Study Details

PMID:22526572
Participants:24
Impact:alloderm reduced from 63.7 to 34.2 (≈ −29.5 points); silastic reduced from 61.4 to 33.6 (≈ −27.8 points)
Trust score:3/5

arterial stiffness (baPWV)

1 evidences

Oral chicken collagen hydrolysate (2.9 g/day) for 18 weeks reduced arterial stiffness and blood pressure and increased serum nitric oxide versus placebo.

Trust comment: Placebo-controlled human study with moderate sample and significant endpoints, but limited detail on magnitude in abstract.

Study Details

PMID:23563560
Participants:58
Impact:significantly lower change in test group vs placebo (ΔbaPWV decreased)
Trust score:3/5

blood pressure

1 evidences

Oral chicken collagen hydrolysate (2.9 g/day) for 18 weeks reduced arterial stiffness and blood pressure and increased serum nitric oxide versus placebo.

Trust comment: Placebo-controlled human study with moderate sample and significant endpoints, but limited detail on magnitude in abstract.

Study Details

PMID:23563560
Participants:58
Impact:test group blood pressure lower than placebo (statistically significant)
Trust score:3/5

serum nitric oxide

1 evidences

Oral chicken collagen hydrolysate (2.9 g/day) for 18 weeks reduced arterial stiffness and blood pressure and increased serum nitric oxide versus placebo.

Trust comment: Placebo-controlled human study with moderate sample and significant endpoints, but limited detail on magnitude in abstract.

Study Details

PMID:23563560
Participants:58
Impact:increased in test group after treatment (statistically significant)
Trust score:3/5

spinal BMD

1 evidences

GH dosing altered bone density and increased biochemical collagen markers over 12 months in adults with GH deficiency.

Trust comment: Randomized controlled human trials with measured clinical and biochemical endpoints, moderate sample size.

Study Details

PMID:12153608
Participants:58
Impact:placebo -2.5%; low dose +2.4%; medium dose +3.1%; high dose -0.2% (ns)
Trust score:4/5

forearm BMD

1 evidences

GH dosing altered bone density and increased biochemical collagen markers over 12 months in adults with GH deficiency.

Trust comment: Randomized controlled human trials with measured clinical and biochemical endpoints, moderate sample size.

Study Details

PMID:12153608
Participants:58
Impact:high dose -4.9% (P<0.05)
Trust score:4/5

collagen turnover markers (PICP, ICTP, PIIINP)

1 evidences

GH dosing altered bone density and increased biochemical collagen markers over 12 months in adults with GH deficiency.

Trust comment: Randomized controlled human trials with measured clinical and biochemical endpoints, moderate sample size.

Study Details

PMID:12153608
Participants:58
Impact:increased (significant, sustained)
Trust score:4/5

skin and subcutaneous vessel AGEs

1 evidences

Daily fish-derived collagen peptides for 12 weeks lowered skin/vessel AGEs and slightly improved insulin resistance versus placebo.

Trust comment: Double-blind randomized placebo-controlled human study but small sample size (n=31).

Study Details

PMID:37245058
Participants:31
Impact:decreased (significant vs placebo)
Trust score:4/5

insulin resistance (HOMA-R)

1 evidences

Daily fish-derived collagen peptides for 12 weeks lowered skin/vessel AGEs and slightly improved insulin resistance versus placebo.

Trust comment: Double-blind randomized placebo-controlled human study but small sample size (n=31).

Study Details

PMID:37245058
Participants:31
Impact:slightly decreased (trend vs placebo)
Trust score:4/5

body and blood composition

1 evidences

Daily fish-derived collagen peptides for 12 weeks lowered skin/vessel AGEs and slightly improved insulin resistance versus placebo.

Trust comment: Double-blind randomized placebo-controlled human study but small sample size (n=31).

Study Details

PMID:37245058
Participants:31
Impact:no significant change
Trust score:4/5

small hematoma rate (24 h)

1 evidences

Collagen plug (VasoSeal) markedly shortened time to hemostasis after PTCA versus manual compression, with similar overall local complication rates.

Trust comment: Prospective randomized study with substantial sample size (n=150); clear clinical endpoints.

Study Details

PMID:10745613
Participants:150
Impact:collagen 23% vs control 32% (reduced)
Trust score:4/5

large hematoma rate / major complication

1 evidences

Collagen plug (VasoSeal) markedly shortened time to hemostasis after PTCA versus manual compression, with similar overall local complication rates.

Trust comment: Prospective randomized study with substantial sample size (n=150); clear clinical endpoints.

Study Details

PMID:10745613
Participants:150
Impact:collagen 4% vs control 0% (increased); one pseudoaneurysm in collagen group
Trust score:4/5

bone regeneration/ossification

1 evidences

Bio-Oss Collagen placed into extraction sockets produced earlier-stage bone formation and denser tissue allowing implant placement after eight weeks.

Trust comment: Randomized controlled clinical trial with 66 patients and histologic/molecular endpoints; results credible though many outcomes reported qualitatively.

Study Details

PMID:33771659
Participants:66
Impact:earlier ossification; more samples with woven bone in treated sockets (qualitative increase)
Trust score:4/5

tissue volume/density

1 evidences

Bio-Oss Collagen placed into extraction sockets produced earlier-stage bone formation and denser tissue allowing implant placement after eight weeks.

Trust comment: Randomized controlled clinical trial with 66 patients and histologic/molecular endpoints; results credible though many outcomes reported qualitatively.

Study Details

PMID:33771659
Participants:66
Impact:increased tissue densification and greater volume fraction in treated sockets (qualitative)
Trust score:4/5

angiogenic/osteogenic markers (Runx2, VEGF, CD34, caveolin-1)

1 evidences

Bio-Oss Collagen placed into extraction sockets produced earlier-stage bone formation and denser tissue allowing implant placement after eight weeks.

Trust comment: Randomized controlled clinical trial with 66 patients and histologic/molecular endpoints; results credible though many outcomes reported qualitatively.

Study Details

PMID:33771659
Participants:66
Impact:Runx2 and VEGF mRNA increased in patients <50 years; CD34 and caveolin-1 protein decreased in treated sockets (significant)
Trust score:4/5

urinary NTx (bone resorption marker)

1 evidences

Alendronate reduced pain and improved pain-related quality of life and increased lumbar BMD more than alfacalcidol in postmenopausal osteoporotic women.

Trust comment: Randomized comparative crossover but open-label and small sample, limiting robustness.

Study Details

PMID:20458350
Participants:34
Impact:-57% (alendronate) vs -18% (alfacalcidol)
Trust score:3/5

wound closure rate

1 evidences

Randomized trial in chronic diabetic foot ulcers: a porcine-derived purified reconstituted bilayer matrix (ECM product) produced higher 12-week healing rates, faster healing, and much greater wound area reduction than standard collagen-alginate dressing.

Trust comment: Randomized controlled trial showing large effects for a collagen-containing ECM product, but small sample (n=40) and industry funding/COI limit confidence.

Study Details

PMID:35001559
Participants:40
Impact:+55 percentage points (85% vs 30% healed at 12 weeks)
Trust score:3/5

wound events / complications

1 evidences

Porcine acellular dermal (Strattice™) mesh gave similar early complication and 3-month pain scores to synthetic mesh, with less immediate postoperative pain days 1–3.

Trust comment: Randomized, double-blind multicenter trial with 172 patients; good design and clinically relevant endpoints but short-term follow-up in this early report.

Study Details

PMID:23543334
Participants:172
Impact:no difference at 3 months (Strattice 15 events vs Ultrapro 16 events)
Trust score:4/5

postoperative pain (early, days 1–3)

1 evidences

Porcine acellular dermal (Strattice™) mesh gave similar early complication and 3-month pain scores to synthetic mesh, with less immediate postoperative pain days 1–3.

Trust comment: Randomized, double-blind multicenter trial with 172 patients; good design and clinically relevant endpoints but short-term follow-up in this early report.

Study Details

PMID:23543334
Participants:172
Impact:significantly less with Strattice (early postoperative period)
Trust score:4/5

activity impairment (AAS)

1 evidences

Porcine acellular dermal (Strattice™) mesh gave similar early complication and 3-month pain scores to synthetic mesh, with less immediate postoperative pain days 1–3.

Trust comment: Randomized, double-blind multicenter trial with 172 patients; good design and clinically relevant endpoints but short-term follow-up in this early report.

Study Details

PMID:23543334
Participants:172
Impact:improvement postoperatively: Strattice 31% vs Ultrapro 37%
Trust score:4/5

elastase activity in wound exudate

1 evidences

ORC/collagen matrix applied to pressure sores accelerated healing and reduced protease (elastase and plasmin) activity in wound exudate versus foam dressing control.

Trust comment: Prospective randomized study in 33 patients showing clinical benefit and correlated biochemical changes; limited sample size but direct clinical relevance for collagen wound matrix.

Study Details

PMID:26011241
Participants:33
Impact:decreased with ORC/collagen matrix vs control
Trust score:4/5

plasmin activity in wound exudate

1 evidences

ORC/collagen matrix applied to pressure sores accelerated healing and reduced protease (elastase and plasmin) activity in wound exudate versus foam dressing control.

Trust comment: Prospective randomized study in 33 patients showing clinical benefit and correlated biochemical changes; limited sample size but direct clinical relevance for collagen wound matrix.

Study Details

PMID:26011241
Participants:33
Impact:decreased with ORC/collagen matrix vs control
Trust score:4/5

granulation tissue

1 evidences

Adjunctive collagen+alginate dressing with compression increased granulation tissue and reduced ulcer area more than alginate alone over 12 weeks.

Trust comment: Randomized controlled study with 40 completers showing clinically meaningful wound improvements with collagen dressing; moderate quality but small sample.

Study Details

PMID:26551647
Participants:40
Impact:group A +65% vs group B +38% (increase)
Trust score:4/5

ulcer area reduction

1 evidences

Adjunctive collagen+alginate dressing with compression increased granulation tissue and reduced ulcer area more than alginate alone over 12 weeks.

Trust comment: Randomized controlled study with 40 completers showing clinically meaningful wound improvements with collagen dressing; moderate quality but small sample.

Study Details

PMID:26551647
Participants:40
Impact:mean area reduced ~45% (group A) vs ~20% (group B) at 12 weeks
Trust score:4/5

safety/tolerance

1 evidences

Adjunctive collagen+alginate dressing with compression increased granulation tissue and reduced ulcer area more than alginate alone over 12 weeks.

Trust comment: Randomized controlled study with 40 completers showing clinically meaningful wound improvements with collagen dressing; moderate quality but small sample.

Study Details

PMID:26551647
Participants:40
Impact:no significant side effects detected in either group
Trust score:4/5

upper lip volume

1 evidences

Randomised double-blind study comparing porcine/bovine collagen fillers and hyaluronic acid for upper lip wrinkles; all treatments increased lip volume and reduced wrinkles, Perlane showed greatest and most sustained volume.

Trust comment: Randomised double-blind trial with objective 3D measures and reasonable sample size though single-centre.

Study Details

PMID:18986859
Participants:79
Impact:+increase (Perlane > PRI1/PRI2/Zyplast)
Trust score:4/5

root coverage (RC)

1 evidences

Porcine-derived collagen matrix (PDCM) produced better root coverage and less pain/time than connective tissue grafts in smokers.

Trust comment: Randomized controlled clinical trial with clear clinical measures but small sample size (28 patients).

Study Details

PMID:36057652
Participants:28
Impact:greater improvement with PDCM (P<0.001)
Trust score:4/5

24h chest tube drainage

1 evidences

Randomised comparison in high-bleeding-risk cardiac surgery showing microfibrillar collagen powder (Colgel) substantially reduced early and total postoperative chest drainage versus Surgicel.

Trust comment: Randomised clinical study of moderate size with clear, clinically relevant and statistically significant outcomes.

Study Details

PMID:14502137
Participants:71
Impact:Colgel 373 ±143 mL vs Surgicel 571 ±144 mL (P = .01) decreased with Colgel
Trust score:4/5

total postoperative chest drainage

1 evidences

Randomised comparison in high-bleeding-risk cardiac surgery showing microfibrillar collagen powder (Colgel) substantially reduced early and total postoperative chest drainage versus Surgicel.

Trust comment: Randomised clinical study of moderate size with clear, clinically relevant and statistically significant outcomes.

Study Details

PMID:14502137
Participants:71
Impact:Colgel 423 ±154 mL vs Surgicel 677 ±128 mL (P = .01) decreased with Colgel
Trust score:4/5

early postoperative blood loss (first 3 h)

1 evidences

Randomised comparison in high-bleeding-risk cardiac surgery showing microfibrillar collagen powder (Colgel) substantially reduced early and total postoperative chest drainage versus Surgicel.

Trust comment: Randomised clinical study of moderate size with clear, clinically relevant and statistically significant outcomes.

Study Details

PMID:14502137
Participants:71
Impact:Colgel 132 ±41 mL vs Surgicel 228 ±57 mL (P < .001) decreased with Colgel
Trust score:4/5

surgical wound infection rate

1 evidences

Randomised trial showing primary closure with collagen‑gentamicin implant reduced surgical wound infections and shortened healing time versus open wound care in contaminated abdominal wounds.

Trust comment: Randomised study with adequate sample size showing significant clinical benefits, though detailed numeric rates not reported here.

Study Details

PMID:9880419
Participants:73
Impact:decrease (collagen-gentamicin implant significantly reduced infection rate; P < 0.01)
Trust score:4/5

period of disability

1 evidences

Randomised trial showing primary closure with collagen‑gentamicin implant reduced surgical wound infections and shortened healing time versus open wound care in contaminated abdominal wounds.

Trust comment: Randomised study with adequate sample size showing significant clinical benefits, though detailed numeric rates not reported here.

Study Details

PMID:9880419
Participants:73
Impact:decrease (shortened)
Trust score:4/5

mid-buccal vertical site (comparison DBBM vs FDBA)

1 evidences

Randomised trial comparing ARP techniques found that groups using bone graft plus collagen sponge or free gingival graft had less vertical and horizontal bone resorption than graftless treatment after 4 months.

Trust comment: Randomised study with 41 patients and clinically relevant comparisons involving collagen sponge, but limited sample size and short follow-up (4 months).

Study Details

PMID:37227497
Participants:41
Impact:difference adjusted β = 1.07 mm (95%CI 0.01–2.10) favoring xenograft over allograft at buccal central site)
Trust score:3/5

central corneal thickness

3 evidences

Collagen cross-linking provided short-term symptomatic relief, reduced central corneal thickness and caused anterior stromal compaction in PBK patients.

Trust comment: Prospective interventional study with objective measures but small sample and limited duration of effect.

Study Details

PMID:23953101
Participants:24
Impact:decreased from 846.46 μm to 781.0 μm at 1 month (P<0.01)
Trust score:3/5

Corneal collagen cross-linking improved vision and reduced corneal curvature at 6 months versus sham, with expected cellular changes on confocal microscopy.

Trust comment: Prospective randomized sham-controlled trial with objective measures and 6-month follow-up; moderate sample size (43 eyes).

Study Details

PMID:25708282
Participants:43
Impact:decreased by mean 22.7 ± 10.3 µm (P = 0.01)
Trust score:4/5

Accelerated and standard corneal collagen crosslinking produced similar 6-month outcomes for keratoconus (visual acuity, refraction, topography); central corneal thickness was higher in the standard group.

Trust comment: Prospective randomized clinical trial with 62 eyes (31 patients) and 6-month follow-up; well-designed but short-term.

Study Details

PMID:25804580
Participants:31
Impact:higher in standard CXL group (p = 0.025)
Trust score:4/5

endothelial cell density

1 evidences

Corneal collagen cross-linking stabilized progressive keratoconus and reduced corneal steepness over 12 months.

Trust comment: Randomized controlled human trial with objective ophthalmic outcomes; interim analysis and moderate sample size.

Study Details

PMID:18811118
Participants:49
Impact:No significant change
Trust score:4/5

zonal Kmax-3mm (average keratometry)

1 evidences

Contralateral randomized trial in Down syndrome patients with keratoconus comparing standard vs accelerated corneal cross-linking over 3 years; both flattened corneas similarly but standard better preserved corneal stiffness.

Trust comment: Contralateral randomized design and 3-year follow-up are strengths, but sample size is small and baseline biomechanical imbalance may confound some results.

Study Details

PMID:35686709
Participants:27
Impact:3-year change: accelerated −0.06 ± 0.75 D vs standard −0.35 ± 0.94 D (no significant difference)
Trust score:3/5

stress-strain index (corneal stiffness)

1 evidences

Contralateral randomized trial in Down syndrome patients with keratoconus comparing standard vs accelerated corneal cross-linking over 3 years; both flattened corneas similarly but standard better preserved corneal stiffness.

Trust comment: Contralateral randomized design and 3-year follow-up are strengths, but sample size is small and baseline biomechanical imbalance may confound some results.

Study Details

PMID:35686709
Participants:27
Impact:3-year change: accelerated −0.30 ± 0.32 vs standard −0.11 ± 0.21 (standard showed less decline; significant)
Trust score:3/5

other biomechanical indices (integrated radius, deformation amplitude ratio-2mm)

1 evidences

Contralateral randomized trial in Down syndrome patients with keratoconus comparing standard vs accelerated corneal cross-linking over 3 years; both flattened corneas similarly but standard better preserved corneal stiffness.

Trust comment: Contralateral randomized design and 3-year follow-up are strengths, but sample size is small and baseline biomechanical imbalance may confound some results.

Study Details

PMID:35686709
Participants:27
Impact:greater adverse 3-year changes with accelerated CXL (numerical differences reported; P < .0167)
Trust score:3/5

leg lean mass

1 evidences

In older adults under energy restriction and reduced activity, collagen peptides did not prevent leg muscle loss or restore muscle protein synthesis during recovery; whey protein did restore these measures.

Trust comment: Randomized controlled trial with objective endpoints and direct comparison of collagen peptides vs whey; small sample limits precision.

Study Details

PMID:30289425
Participants:31
Impact:decreased during energy restriction and step-reduction (P<0.001); no recovery increase with collagen peptides (increase during recovery seen only with whey)
Trust score:4/5

muscle protein synthesis (integrated MPS)

1 evidences

In older adults under energy restriction and reduced activity, collagen peptides did not prevent leg muscle loss or restore muscle protein synthesis during recovery; whey protein did restore these measures.

Trust comment: Randomized controlled trial with objective endpoints and direct comparison of collagen peptides vs whey; small sample limits precision.

Study Details

PMID:30289425
Participants:31
Impact:decreased during energy restriction and step-reduction (P<0.01); did not increase during recovery with collagen peptides (increase during recovery seen only with whey)
Trust score:4/5

Fusion rate

2 evidences

Pivotal randomized FDA IDE trial comparing i-Factor (P‑15 synthetic collagen fragment bone graft) versus local autograft in single-level anterior cervical fusion with 2-year follow-up; similar clinical outcomes and fusion rates, with a higher composite overall success for i-Factor.

Trust comment: Randomized FDA IDE multicenter trial with large sample and 2-year follow-up; direct test of a collagen-containing device (P-15), but industry/device context noted.

Study Details

PMID:28945914
Participants:319
Impact:i-Factor 97.30% vs autograft 94.44% (P=0.2513, NS)
Trust score:4/5

A randomized multicenter FDA IDE trial found the i-Factor bone graft (contains a synthetic collagen fragment P-15) noninferior to autograft for single-level ACDF with high fusion rates and similar safety; overall composite success was higher with i-Factor.

Trust comment: Large randomized, multicenter FDA pivotal trial showing noninferiority and higher overall success for a device that includes a synthetic collagen fragment (P-15); well-conducted with robust endpoints.

Study Details

PMID:26825787
Participants:319
Impact:i-Factor 88.97% vs autograft 85.82% (noninferior)
Trust score:4/5

pain (NRS)

1 evidences

MIV-711 did not improve pain but significantly reduced bone area progression, reduced cartilage thinning, and lowered collagen biomarker levels.

Trust comment: Randomized phase 2a trial with imaging and biomarker endpoints; moderate sample size but relatively short duration.

Study Details

PMID:31887743
Participants:244
Impact:No significant change: placebo -1.4 vs MIV-711 100 mg -1.7 vs 200 mg -1.5
Trust score:4/5

recurrence rate (abscess/fistula)

1 evidences

Adding a gentamicin‑collagen implant (Gentacoll) to clindamycin did not reduce abscess/fistula recurrence compared with clindamycin alone.

Trust comment: Randomized clinical trial with moderate sample size and objective clinical endpoint but negative result for benefit of the collagen implant.

Study Details

PMID:7720448
Participants:107
Impact:Gentacoll 22% (12/55) vs control 17% (9/52); difference not statistically significant
Trust score:3/5

Wound width and depth (1 week)

1 evidences

Smokers had smaller, more superficial punch wounds and lower vitamin C and PINP (a collagen synthesis marker); smoking cessation increased wound depth, vitamin C, and PINP; nicotine patch had no detectable effect.

Trust comment: Randomized, double-blinded design for smoking interventions with 48 smokers and 30 never-smokers and multiple clinical and biochemical collagen-related endpoints.

Study Details

PMID:20347467
Participants:78
Impact:Smokers: 3.1 ± 0.1 mm wide and 1.3 ± 0.1 mm deep vs never smokers 3.7 ± 0.1 mm and 1.5 ± 0.1 mm (P < .01); abstinent smokers depth increased to 1.4 ± 0.1 mm (P = .02 vs smokers)
Trust score:4/5

vitamin C (plasma)

1 evidences

Smokers had smaller, more superficial punch wounds and lower vitamin C and PINP (a collagen synthesis marker); smoking cessation increased wound depth, vitamin C, and PINP; nicotine patch had no detectable effect.

Trust comment: Randomized, double-blinded design for smoking interventions with 48 smokers and 30 never-smokers and multiple clinical and biochemical collagen-related endpoints.

Study Details

PMID:20347467
Participants:78
Impact:Lower in smokers (50.5 ± 9.0 µmol/L) vs never smokers (68.8 ± 14.5 µmol/L); increased after cessation (P < .001)
Trust score:4/5

PINP (procollagen I N-propeptide)

1 evidences

Smokers had smaller, more superficial punch wounds and lower vitamin C and PINP (a collagen synthesis marker); smoking cessation increased wound depth, vitamin C, and PINP; nicotine patch had no detectable effect.

Trust comment: Randomized, double-blinded design for smoking interventions with 48 smokers and 30 never-smokers and multiple clinical and biochemical collagen-related endpoints.

Study Details

PMID:20347467
Participants:78
Impact:Lower in smokers (52.7 ± 6.6 ng/mL) vs never smokers (64.7 ± 4.7 ng/mL); increased after cessation
Trust score:4/5

Skin architecture/texture (histology)

1 evidences

Daily oral nutricosmeceutical (collagen peptides + antioxidants) for 90 days improved skin elasticity and texture versus placebo.

Trust comment: Double-blind randomized placebo-controlled trial with good sample size (n=120); product combined collagen peptides with antioxidants which may confound isolated collagen effect.

Study Details

PMID:28528342
Participants:120
Impact:Improved vs placebo (reported histological improvement)
Trust score:4/5

Patient-reported outcomes

1 evidences

Daily oral nutricosmeceutical (collagen peptides + antioxidants) for 90 days improved skin elasticity and texture versus placebo.

Trust comment: Double-blind randomized placebo-controlled trial with good sample size (n=120); product combined collagen peptides with antioxidants which may confound isolated collagen effect.

Study Details

PMID:28528342
Participants:120
Impact:Positive self-assessment feedback vs placebo
Trust score:4/5

horizontal ridge width preservation

1 evidences

In adults needing tooth extraction, DBBMC+native bilayer collagen membrane preserved more horizontal ridge width and healed with smaller incision gaps than DFDBA+cross-linked collagen after 6 months.

Trust comment: Randomized multicentre RCT (n=40) with prespecified endpoints and a statistically significant primary outcome; well-described methods.

Study Details

PMID:27617409
Participants:40
Impact:+1.76 mm (mean difference DBBMC+NBCM vs DFDBA+RECXC; stent Δ baseline→6mo: 6.71 vs 4.95 mm; p=0.0256)
Trust score:4/5

vertical ridge height preservation

1 evidences

In adults needing tooth extraction, DBBMC+native bilayer collagen membrane preserved more horizontal ridge width and healed with smaller incision gaps than DFDBA+cross-linked collagen after 6 months.

Trust comment: Randomized multicentre RCT (n=40) with prespecified endpoints and a statistically significant primary outcome; well-described methods.

Study Details

PMID:27617409
Participants:40
Impact:+0.95 mm (buccal vertical mean Δ DBBMC vs DFDBA: 6.24 vs 5.29 mm; not significant p=0.3818)
Trust score:4/5

incision line gap / wound closure

1 evidences

In adults needing tooth extraction, DBBMC+native bilayer collagen membrane preserved more horizontal ridge width and healed with smaller incision gaps than DFDBA+cross-linked collagen after 6 months.

Trust comment: Randomized multicentre RCT (n=40) with prespecified endpoints and a statistically significant primary outcome; well-described methods.

Study Details

PMID:27617409
Participants:40
Impact:smaller gaps with DBBMC at 1 month: 0.79 vs 2.26 mm (difference 1.47 mm, p=0.0427); higher frequency closed 14/19 vs 8/21 (p=0.0309)
Trust score:4/5

Subject Global Evaluation (human collagen)

1 evidences

Human (injectable) collagen produced early improvement in nasolabial folds that largely wore off by 13 months, whereas poly-L-lactic acid maintained improvement much longer.

Trust comment: Large randomized multicenter trial with long follow-up and clear, clinically meaningful patient-reported endpoints.

Study Details

PMID:21460676
Participants:233
Impact:96% at week 3 → 15% at month 13 (decline of 81 percentage points; reported as 84% decline)
Trust score:4/5

Subject Satisfaction

1 evidences

Human (injectable) collagen produced early improvement in nasolabial folds that largely wore off by 13 months, whereas poly-L-lactic acid maintained improvement much longer.

Trust comment: Large randomized multicenter trial with long follow-up and clear, clinically meaningful patient-reported endpoints.

Study Details

PMID:21460676
Participants:233
Impact:Significantly lower for human collagen versus PLLA from week 3 through month 13 (p<0.01); numeric values for collagen group not provided in excerpt
Trust score:4/5

percentage of vital bone

1 evidences

At 16 weeks, the hydroxyapatite–sugar cross-linked porcine collagen matrix group showed more vital bone formation than the bovine-derived xenograft+collagen matrix group; ridge dimensions were similar.

Trust comment: Randomized controlled trial with histologic primary outcome and statistically significant result (n enrolled 54, 44 completed).

Study Details

PMID:35661358
Participants:44
Impact:Group B (HA–collagen) 39.3% ± 17.8 vs Group A (bovine xenograft+collagen) 26.8% ± 15.8; mean difference ≈ +12.5 percentage points (p=0.02)
Trust score:4/5

alveolar ridge dimensional change

1 evidences

At 16 weeks, the hydroxyapatite–sugar cross-linked porcine collagen matrix group showed more vital bone formation than the bovine-derived xenograft+collagen matrix group; ridge dimensions were similar.

Trust comment: Randomized controlled trial with histologic primary outcome and statistically significant result (n enrolled 54, 44 completed).

Study Details

PMID:35661358
Participants:44
Impact:No statistically significant difference between groups
Trust score:4/5

recession depth reduction

1 evidences

Split-mouth randomized trial comparing rhPDGF-BB + beta-TCP + bioabsorbable collagen dressing versus connective tissue graft for gingival recession; both improved clinically, with some measures favoring CTG and others favoring the test.

Trust comment: Well-designed split-mouth RCT with histologic corroboration but modest sample size; reliable within its surgical context.

Study Details

PMID:19335074
Participants:30
Impact:test −2.9±0.5 mm; control −3.3±0.6 mm (P=0.009 favoring control)
Trust score:4/5

Steepest keratometry (K-max)

1 evidences

Corneal collagen cross-linking stabilized progressive keratoconus and reduced corneal steepness over 12 months.

Trust comment: Randomized controlled human trial with objective ophthalmic outcomes; interim analysis and moderate sample size.

Study Details

PMID:18811118
Participants:49
Impact:−0.74 D (3 mo), −0.92 D (6 mo), −1.45 D (12 mo) in treated eyes
Trust score:4/5

Collagen content

1 evidences

Daily C. rabens extract (180 mg) for 4 weeks improved several skin-aging measures including reduced wrinkles and increased collagen-associated parameters compared with placebo.

Trust comment: Randomized, double-blind, placebo-controlled human trial with complete follow-up, but small sample and short (4-week) duration limit generalizability.

Study Details

PMID:35807836
Participants:40
Impact:Significant increase from baseline in both groups, with a more prominent increase in treatment vs placebo
Trust score:4/5

St Mark's incontinence score (Permacol)

1 evidences

Submucosal collagen injection (Permacol®) produced small improvement in incontinence but was markedly less effective than sacral neuromodulation at 6 months.

Trust comment: Single-blinded randomized controlled trial with clear between-group differences showing inferior efficacy of collagen injection (Permacol) compared with SNM.

Study Details

PMID:28211186
Participants:58
Impact:−2.3 points at 6 months (Permacol) vs −11.2 (SNM); between-group difference 8.9 points favoring SNM
Trust score:4/5

Disease-specific quality of life (FIQL)

1 evidences

Submucosal collagen injection (Permacol®) produced small improvement in incontinence but was markedly less effective than sacral neuromodulation at 6 months.

Trust comment: Single-blinded randomized controlled trial with clear between-group differences showing inferior efficacy of collagen injection (Permacol) compared with SNM.

Study Details

PMID:28211186
Participants:58
Impact:Smaller improvements with Permacol vs SNM across FIQL domains
Trust score:4/5

Urinary incontinence score (ICIQ-UI-SF)

1 evidences

Submucosal collagen injection (Permacol®) produced small improvement in incontinence but was markedly less effective than sacral neuromodulation at 6 months.

Trust comment: Single-blinded randomized controlled trial with clear between-group differences showing inferior efficacy of collagen injection (Permacol) compared with SNM.

Study Details

PMID:28211186
Participants:58
Impact:Difference 5.0 points favoring SNM (P=0.002)
Trust score:4/5

Defect resolution

2 evidences

Use of a bovine bone graft plus a bioabsorbable collagen barrier led to greater soft- and hard-tissue improvement than open-flap debridement over the study period.

Trust comment: Small clinical study with direct human data and clear measurements but limited sample size (21 patients) and unclear randomisation details.

Study Details

PMID:11829390
Participants:21
Impact:82.7% (BO/BG) vs 42.5% (OFD)
Trust score:3/5

Adding autogenous bone (with or without bioactive glass) to a collagen membrane led to greater periodontal defect healing than collagen membrane alone.

Trust comment: Randomized treatment of 32 defects in 22 subjects; small sample but randomized and clinically relevant outcomes.

Study Details

PMID:22167034
Participants:22
Impact:Greater defect resolution in test groups compared with collagen membrane alone
Trust score:3/5

Bone level change (prosthesis to 1 year)

1 evidences

A novel non-cross-linked collagen membrane (CXP) showed similar clinical performance to a reference membrane for guided bone regeneration at implant sites up to 1 year.

Trust comment: Multicenter randomized controlled trial demonstrating non-inferiority of a collagen membrane with 1-year follow-up.

Study Details

PMID:30927498
Participants:49
Impact:CXP +0.01 mm vs BG +0.42 mm (no significant difference)
Trust score:4/5

Implant cumulative survival rate

1 evidences

A novel non-cross-linked collagen membrane (CXP) showed similar clinical performance to a reference membrane for guided bone regeneration at implant sites up to 1 year.

Trust comment: Multicenter randomized controlled trial demonstrating non-inferiority of a collagen membrane with 1-year follow-up.

Study Details

PMID:30927498
Participants:49
Impact:100% at 1 year (n=42)
Trust score:4/5

Persistent hypotony

1 evidences

Use of a collagen matrix implant in trabeculectomy produced similar IOP-lowering efficacy to mitomycin-C but a significantly lower risk of sustained hypotony.

Trust comment: Large multicenter randomized clinical trial with robust design and a clinically important safety advantage for collagen matrix.

Study Details

PMID:28034308
Participants:93
Impact:MMC: 9 subjects vs CM: 0 subjects (significantly higher risk with MMC; p=0.002)
Trust score:5/5

IOP-lowering success (complete)

1 evidences

Use of a collagen matrix implant in trabeculectomy produced similar IOP-lowering efficacy to mitomycin-C but a significantly lower risk of sustained hypotony.

Trust comment: Large multicenter randomized clinical trial with robust design and a clinically important safety advantage for collagen matrix.

Study Details

PMID:28034308
Participants:93
Impact:No significant difference between collagen matrix and MMC in complete success rates
Trust score:5/5

urine NTX (type I collagen telopeptide)

1 evidences

In patients starting glucocorticoids, alfacalcidol (a vitamin D analog) increased some bone formation markers but BMD fell with alfacalcidol while it increased with alendronate over 18 months.

Trust comment: Large randomized, double‑blind clinical trial with standard biochemical and BMD endpoints; good internal validity though population limited to glucocorticoid users.

Study Details

PMID:17407214
Participants:201
Impact:NTx decreased significantly in both treatment groups
Trust score:4/5

buccal soft-tissue surface area loss

1 evidences

In ridge preservation, both collagen barrier types allowed some soft-tissue contour loss; the collagen matrix seal showed slightly less loss than the collagen sponge but differences were not statistically significant.

Trust comment: Randomized controlled trial with objective volumetric measures directly comparing collagen products; modest sample size (n=28) limits precision.

Study Details

PMID:32369569
Participants:28
Impact:CMS 71.44 ± 1189.09 mm2 vs CS 139.56 ± 557.92 mm2 (no significant difference)
Trust score:4/5

buccal soft-tissue volume loss

1 evidences

In ridge preservation, both collagen barrier types allowed some soft-tissue contour loss; the collagen matrix seal showed slightly less loss than the collagen sponge but differences were not statistically significant.

Trust comment: Randomized controlled trial with objective volumetric measures directly comparing collagen products; modest sample size (n=28) limits precision.

Study Details

PMID:32369569
Participants:28
Impact:CMS 239.58 ± 231.89 mm3 vs CS 337.23 ± 310.18 mm3 (no significant difference)
Trust score:4/5

mean buccal soft-tissue linear loss

1 evidences

In ridge preservation, both collagen barrier types allowed some soft-tissue contour loss; the collagen matrix seal showed slightly less loss than the collagen sponge but differences were not statistically significant.

Trust comment: Randomized controlled trial with objective volumetric measures directly comparing collagen products; modest sample size (n=28) limits precision.

Study Details

PMID:32369569
Participants:28
Impact:CMS 0.88 ± 0.52 mm vs CS 1.63 ± 1.03 mm (no significant difference)
Trust score:4/5

trabecular BMC

1 evidences

Adding collagen peptides to calcium + vitamin D for 12 months increased trabecular bone mass and vBMD at the tibia, prevented spine aBMD decline, and reduced bone turnover versus calcium + vitamin D alone.

Trust comment: Randomized prospective 12-month study with direct bone density and turnover measures but modest sample size.

Study Details

PMID:34980546
Participants:51
Impact:+5.24% ±6.48% (Group A; significant vs Group B)
Trust score:4/5

trabecular vBMD

1 evidences

Adding collagen peptides to calcium + vitamin D for 12 months increased trabecular bone mass and vBMD at the tibia, prevented spine aBMD decline, and reduced bone turnover versus calcium + vitamin D alone.

Trust comment: Randomized prospective 12-month study with direct bone density and turnover measures but modest sample size.

Study Details

PMID:34980546
Participants:51
Impact:+2.54% ±3.43% (Group A; p=0.02 vs Group B)
Trust score:4/5

spinal aBMD

1 evidences

Adding collagen peptides to calcium + vitamin D for 12 months increased trabecular bone mass and vBMD at the tibia, prevented spine aBMD decline, and reduced bone turnover versus calcium + vitamin D alone.

Trust comment: Randomized prospective 12-month study with direct bone density and turnover measures but modest sample size.

Study Details

PMID:34980546
Participants:51
Impact:increased (mean aBMD at the spine higher; p=0.01 vs Group B)
Trust score:4/5

maximum simulated keratometry (K steep)

1 evidences

Epithelium-off CXL produced greater flattening of maximum keratometry at 24 months than transepithelial CXL, with no significant difference in corrected visual acuity.

Trust comment: Prospective randomized trial with 24-month follow-up and objective topographic/visual outcomes; good design and follow-up rate.

Study Details

PMID:27388250
Participants:131
Impact:epithelium-off: −1.52±0.66 D vs transepithelial: −0.54±0.58 D (greater improvement with epithelium-off; p=0.032)
Trust score:4/5

best spectacle-corrected visual acuity (BSCVA)

2 evidences

Corneal collagen cross-linking halted progression of keratoconus over 3 years, flattening Kmax and improving visual acuity compared with controls.

Trust comment: Large randomized controlled trial with 3-year follow-up and objective clinical endpoints, providing robust evidence of efficacy.

Study Details

PMID:24393351
Participants:94
Impact:improved by −0.09 logMAR at 36 months (p=0.006)
Trust score:5/5

Epithelium-off CXL produced greater flattening of maximum keratometry at 24 months than transepithelial CXL, with no significant difference in corrected visual acuity.

Trust comment: Prospective randomized trial with 24-month follow-up and objective topographic/visual outcomes; good design and follow-up rate.

Study Details

PMID:27388250
Participants:131
Impact:no significant difference between groups (−0.18±0.09 vs −0.14±0.08 logMAR; p=0.4978)
Trust score:4/5

probing pocket depth

2 evidences

Split-mouth randomized study in 40 patients comparing scaling/root planing alone versus adjunctive collagen-based tetracycline fibers for chronic periodontitis over 3 months.

Trust comment: Direct clinical use of a collagen-based delivery matrix in humans with a randomized split-mouth design; moderate quality but short follow-up and adjunctive antibiotic confounds collagen-specific effects.

Study Details

PMID:25044345
Participants:40
Impact:Greater reduction with collagen-based tetracycline adjunct versus scaling/root planing alone over 3 months (reported clinically significant)
Trust score:3/5

Collagen membranes (native vs ribosome-crosslinked) gave similar clinical improvements in periodontal defect regeneration at 6 months.

Trust comment: Randomized clinical trial with objective periodontal endpoints and adequate sample size, 6-month follow-up.

Study Details

PMID:38962931
Participants:80
Impact:NCM 4.3 ±1.1 mm; RCCM 4.2 ±1.0 mm (improved from baseline, no between-group difference)
Trust score:4/5

erythema

2 evidences

Topical product containing collagen tripeptide improved objective skin barrier measures and reduced symptoms of sensitive atopic skin versus placebo over 4 weeks.

Trust comment: Randomized double-blind placebo-controlled human trial but small (n=40) and short duration (4 weeks), so moderate confidence.

Study Details

PMID:19496838
Participants:40
Impact:decreased (P<0.0006)
Trust score:3/5

Double-blind randomized trial of tretinoin 0.05% lotion vs vehicle (vehicle contained soluble collagen among other hydrators) for chest photorejuvenation; both active and vehicle groups improved similarly by 180 days with mild, transient erythema higher in active at day 90.

Trust comment: Randomized double-blind vehicle-controlled human trial but small sample and vehicle contained collagen, complicating attribution of effects to tretinoin vs vehicle.

Study Details

PMID:35674757
Participants:29
Impact:Active had significantly more erythema at day 90 (P<0.001); at day 180 active 0.50±0.73 vs vehicle 0.09±0.30
Trust score:4/5

overall complication rate

2 evidences

RCT comparing ADM with vs without basement membrane in immediate prepectoral breast reconstruction: no significant differences in overall complications or shape change; seromas more frequent with basement membrane (10% vs 0%).

Trust comment: Randomized single‑blind trial with moderate sample size directly assessing collagen-containing matrix modifications; limited by borderline/non-significant P for seroma and overall outcome similarity.

Study Details

PMID:39314097
Participants:56
Impact:no significant difference between groups
Trust score:3/5

Randomized trial comparing two acellular dermal matrices (used as collagen-containing grafts) in staged breast reconstruction; similar complication rates but AlloDerm allowed faster expansion.

Trust comment: Largest randomized trial in this surgical context (n=128) with clear endpoints; applicable to collagen-containing acellular matrices used clinically.

Study Details

PMID:25539349
Participants:128
Impact:similar between AlloDerm and DermaMatrix (33.6% vs 38.8%; p = 0.52)
Trust score:4/5

time to completion of expansion

1 evidences

Randomized trial comparing two acellular dermal matrices (used as collagen-containing grafts) in staged breast reconstruction; similar complication rates but AlloDerm allowed faster expansion.

Trust comment: Largest randomized trial in this surgical context (n=128) with clear endpoints; applicable to collagen-containing acellular matrices used clinically.

Study Details

PMID:25539349
Participants:128
Impact:AlloDerm faster: 42 days vs 70 days (p < 0.001)
Trust score:4/5

tissue expander loss

1 evidences

Randomized trial comparing two acellular dermal matrices (used as collagen-containing grafts) in staged breast reconstruction; similar complication rates but AlloDerm allowed faster expansion.

Trust comment: Largest randomized trial in this surgical context (n=128) with clear endpoints; applicable to collagen-containing acellular matrices used clinically.

Study Details

PMID:25539349
Participants:128
Impact:trend toward fewer losses with AlloDerm (5% vs 11.2%; p = 0.11)
Trust score:4/5

epithelial thickness profile regularization

1 evidences

Prospective study showing modest flattening of maximum keratometry and regularization of epithelial thickness profile 6 months after epithelium-off CXL.

Trust comment: Prospective single-center study with adequate sample size (n=93); direct clinical measurements but focused on surgical cross-linking effects rather than collagen supplementation.

Study Details

PMID:29889294
Participants:93
Impact:modest regularization across central 5 mm at 6 months
Trust score:3/5

stromal demarcation line depth

1 evidences

Pulsed accelerated corneal cross-linking produced a deeper stromal demarcation line than continuous accelerated CXL at 3 months.

Trust comment: Controlled clinical comparison with 70 eyes and clear quantitative endpoint, though limited to 3-month outcome.

Study Details

PMID:27027629
Participants:70
Impact:pulsed: 201.11 ± 27.76 µm vs continuous: 159.88 ± 20.86 µm (P < .001)
Trust score:4/5

2D periapical healing (Rud and Molven)

1 evidences

Adding allograft plus collagen membrane increased labial bone regeneration at 1 year compared with surgery alone.

Trust comment: Randomized controlled design with objective imaging endpoints but relatively small sample (30 patients).

Study Details

PMID:40246609
Participants:30
Impact:study group 100% vs control 86.6% (P = .143)
Trust score:4/5

3D periapical healing (modified PENN 3D)

1 evidences

Adding allograft plus collagen membrane increased labial bone regeneration at 1 year compared with surgery alone.

Trust comment: Randomized controlled design with objective imaging endpoints but relatively small sample (30 patients).

Study Details

PMID:40246609
Participants:30
Impact:80% success in both groups
Trust score:4/5

labial alveolar bone regeneration

1 evidences

Adding allograft plus collagen membrane increased labial bone regeneration at 1 year compared with surgery alone.

Trust comment: Randomized controlled design with objective imaging endpoints but relatively small sample (30 patients).

Study Details

PMID:40246609
Participants:30
Impact:study group 17.64 ± 19.76% vs control 4.74 ± 13.14% (P = .023)
Trust score:4/5

buccal soft tissue thickness (GT) increase

1 evidences

Both treatments increased tissue thickness, but connective tissue graft gave greater thickness gain while the collagen matrix resulted in less pain, shorter chair time, and higher satisfaction.

Trust comment: Randomized controlled clinical trial with 60 patients and blinded measurement, providing clinically relevant comparative outcomes.

Study Details

PMID:28548210
Participants:60
Impact:XCM 0.9 ± 0.2 mm vs CTG 1.2 ± 0.3 mm; difference 0.3 mm favoring CTG (p = .0001)
Trust score:4/5

keratinized tissue (KT) amount

1 evidences

Both treatments increased tissue thickness, but connective tissue graft gave greater thickness gain while the collagen matrix resulted in less pain, shorter chair time, and higher satisfaction.

Trust comment: Randomized controlled clinical trial with 60 patients and blinded measurement, providing clinically relevant comparative outcomes.

Study Details

PMID:28548210
Participants:60
Impact:no significant difference between XCM and CTG
Trust score:4/5

post-operative pain and recovery

1 evidences

Both treatments increased tissue thickness, but connective tissue graft gave greater thickness gain while the collagen matrix resulted in less pain, shorter chair time, and higher satisfaction.

Trust comment: Randomized controlled clinical trial with 60 patients and blinded measurement, providing clinically relevant comparative outcomes.

Study Details

PMID:28548210
Participants:60
Impact:XCM associated with less postoperative pain, less painkiller intake, shorter chair time, and higher satisfaction (all p < .05)
Trust score:4/5

arachidonic acid-induced platelet aggregation

1 evidences

Daily willow bark (salicin) modestly reduced platelet aggregation compared with placebo but far less than aspirin; no effect on collagen-induced aggregation.

Trust comment: Randomized double-blind but small groups and limited clinical outcome linkage; laboratory aggregation endpoints are clear.

Study Details

PMID:11345689
Participants:51
Impact:willow 61% vs placebo 78% (≈−17 percentage points vs placebo)
Trust score:3/5

lumbar spine bone mineral density (BMD)

3 evidences

Randomized substudy comparing tamoxifen, exemestane, and anastrozole over 2 years; tamoxifen was associated with lower bone turnover markers (NTX and BAP) versus the two aromatase inhibitors, with BMD trends favoring tamoxifen though not always significant.

Trust comment: Randomized substudy with objective bone markers but limited sample size reduces precision for BMD comparisons.

Study Details

PMID:21430407
Participants:68
Impact:higher in tamoxifen vs exemestane/anastrozole but intergroup differences not statistically significant at 2 years
Trust score:3/5

IV zoledronic acid after ACDF shortened time to osteogenesis, promoted fusion, lowered a collagen degradation marker (CTX) and increased lumbar spine BMD, with improved neck disability scores.

Trust comment: Randomized controlled human study with objective biochemical and BMD outcomes but moderate single-center sample size.

Study Details

PMID:31079567
Participants:43
Impact:increased in ZA group at 12 months (significant)
Trust score:4/5

Randomized placebo-controlled trial of 50 mg DHEA daily for 1 year showing hormonal changes and modest bone benefits in women but not men.

Trust comment: Large randomized placebo-controlled trial with sex-specific biochemical and BMD endpoints; well conducted.

Study Details

PMID:18084691
Participants:225
Impact:positive effect in women after 12 months (p=0.03)
Trust score:4/5

average recession coverage (ARC)

1 evidences

Using a collagen matrix gave good root coverage but resulted in less complete coverage than connective tissue grafts at 6 months.

Trust comment: Randomized human trial directly testing a collagen matrix but small sample and short follow-up limit generalizability.

Study Details

PMID:27424564
Participants:28
Impact:Control (CTG) 95% vs collagen matrix (CM) 91% at 6 months (P<0.05)
Trust score:3/5

complete recession coverage (CRC)

1 evidences

Using a collagen matrix gave good root coverage but resulted in less complete coverage than connective tissue grafts at 6 months.

Trust comment: Randomized human trial directly testing a collagen matrix but small sample and short follow-up limit generalizability.

Study Details

PMID:27424564
Participants:28
Impact:Control 71.4% (10/14) vs CM 14.3% (2/14) at 6 months (P<0.05)
Trust score:3/5

mean recession depth

1 evidences

Using a collagen matrix gave good root coverage but resulted in less complete coverage than connective tissue grafts at 6 months.

Trust comment: Randomized human trial directly testing a collagen matrix but small sample and short follow-up limit generalizability.

Study Details

PMID:27424564
Participants:28
Impact:Control 0.21 mm vs CM 0.39 mm after 6 months (P<0.05)
Trust score:3/5

PIIINP (procollagen type III N-terminal propeptide)

1 evidences

In post-MI patients, eplerenone lowered a blood marker of collagen turnover (PIIINP) when baseline levels were high.

Trust comment: Randomized double-blind trial but this is a secondary analysis on ~52% subset, limiting full generalizability.

Study Details

PMID:28852839
Participants:526
Impact:-0.50 ng/mL between-group change when baseline > median (0.13 ±1.48 vs -0.37 ±1.56 ng/mL; p=0.008)
Trust score:4/5

B-type natriuretic peptide (BNP)

1 evidences

In mild-moderate heart failure, spironolactone lowered BNP and a blood marker of collagen turnover (PIIINP) but worsened renal function and self-reported quality of life over 3 months.

Trust comment: Randomized, double-blind trial measuring a collagen turnover marker (PIIINP) with significant changes, but small sample and short duration limit generalizability.

Study Details

PMID:17126073
Participants:40
Impact:decreased by 53.4 pg/mL in spironolactone group vs +3.3 pg/mL in placebo (P=0.04)
Trust score:3/5

percent defect fill

1 evidences

Randomized study comparing a synthetic PEG hydrogel membrane vs standard collagen membrane for guided bone regeneration around implants; regenerated bone was similar and both membranes performed comparably after 6 months.

Trust comment: Randomized clinical trial in humans but small sample size (n=37) and short-term (6 months); directly compares a collagen membrane as clinical control.

Study Details

PMID:19191793
Participants:37
Impact:PEG: 94.9%; collagen: 96.4% (comparable)
Trust score:3/5

serum osteocalcin (OC)

1 evidences

Randomized feeding study: the DASH diet lowered bone turnover markers and sodium reduction decreased calcium excretion and some bone markers; vitamin D was discussed but not tested.

Trust comment: Large randomized feeding study with controlled diets and clear biomarker changes; shows dietary effects on collagen-derived bone turnover markers (high trust for biomarker outcomes).

Study Details

PMID:14519796
Participants:186
Impact:-8% to -11% on DASH diet (P<0.001)
Trust score:4/5

SD volume (PLLA group)

1 evidences

PLLA injections (a collagen-stimulating filler) reduced stretch-mark area and volume and increased type III collagen without notable inflammation.

Trust comment: Prospective randomized study with objective imaging and histology, but modest sample size and limited follow-up.

Study Details

PMID:40662320
Participants:40
Impact:−1.96 mm³ (T4 vs T0; mean ± s.d. −1.96 ±1.53)
Trust score:4/5

SD area of influence (PLLA group)

1 evidences

PLLA injections (a collagen-stimulating filler) reduced stretch-mark area and volume and increased type III collagen without notable inflammation.

Trust comment: Prospective randomized study with objective imaging and histology, but modest sample size and limited follow-up.

Study Details

PMID:40662320
Participants:40
Impact:−49.43 mm² (T4 vs T0; mean ± s.d. −49.43 ±25.16)
Trust score:4/5

Type III collagen PD (PLLA group)

1 evidences

PLLA injections (a collagen-stimulating filler) reduced stretch-mark area and volume and increased type III collagen without notable inflammation.

Trust comment: Prospective randomized study with objective imaging and histology, but modest sample size and limited follow-up.

Study Details

PMID:40662320
Participants:40
Impact:+4.01 percentage points (T4 11.02% vs T0 7.01%)
Trust score:4/5

Bone-specific alkaline phosphatase

1 evidences

In healthy adults, 8 weeks of high-dose simvastatin (80 mg/day) lowered a serum bone formation marker but did not change a urinary collagen resorption marker.

Trust comment: Randomized trial in 55 healthy adults with clear marker measurements but small sample and short duration.

Study Details

PMID:16088363
Participants:55
Impact:decrease (significant vs other regimens)
Trust score:3/5

Fistula recurrence rate (12 months)

1 evidences

Collagen plug repair had a substantially higher fistula recurrence rate than advancement flap at 12 months; pain improved in both groups.

Trust comment: Large randomized multicentre trial directly testing a collagen product with clear clinical endpoints and adequate follow-up.

Study Details

PMID:28489253
Participants:94
Impact:Plug 66% (27/41) vs flap 38% (15/40)
Trust score:4/5

Anal pain

1 evidences

Collagen plug repair had a substantially higher fistula recurrence rate than advancement flap at 12 months; pain improved in both groups.

Trust comment: Large randomized multicentre trial directly testing a collagen product with clear clinical endpoints and adequate follow-up.

Study Details

PMID:28489253
Participants:94
Impact:Reduced after operation in both groups (no between-group difference reported)
Trust score:4/5

Anal incontinence

1 evidences

Collagen plug repair had a substantially higher fistula recurrence rate than advancement flap at 12 months; pain improved in both groups.

Trust comment: Large randomized multicentre trial directly testing a collagen product with clear clinical endpoints and adequate follow-up.

Study Details

PMID:28489253
Participants:94
Impact:No change during follow-up
Trust score:4/5

Calibrated IBS (myocardial fibrosis signal)

1 evidences

Losartan prevented increases in ultrasonic fibrosis signal seen with other agents and reduced a serum marker ratio consistent with decreased type I collagen turnover.

Trust comment: Randomized comparison with objective imaging and biochemical collagen markers, moderate sample size; findings biologically plausible.

Study Details

PMID:16471172
Participants:39
Impact:No increase after 6 months with losartan (−31.2 to −31.3 dB), whereas enalapril and amlodipine showed significant increases
Trust score:4/5

Procollagen type I carboxy-terminal peptide / collagen type I telopeptide ratio

1 evidences

Losartan prevented increases in ultrasonic fibrosis signal seen with other agents and reduced a serum marker ratio consistent with decreased type I collagen turnover.

Trust comment: Randomized comparison with objective imaging and biochemical collagen markers, moderate sample size; findings biologically plausible.

Study Details

PMID:16471172
Participants:39
Impact:Reduced from 42.6 to 34.4 (p = 0.038) with losartan
Trust score:4/5

Antihypertensive effect

1 evidences

Losartan prevented increases in ultrasonic fibrosis signal seen with other agents and reduced a serum marker ratio consistent with decreased type I collagen turnover.

Trust comment: Randomized comparison with objective imaging and biochemical collagen markers, moderate sample size; findings biologically plausible.

Study Details

PMID:16471172
Participants:39
Impact:Comparable among losartan, enalapril and amlodipine (no significant differences)
Trust score:4/5

bone alkaline phosphatase (bone ALP)

2 evidences

Randomized double-blind trial in postmenopausal women showed risedronate (daily or once-weekly) strongly reduced bone formation and resorption markers over 6 months.

Trust comment: Randomized, double-blind active-controlled trial (n=102) with clear percent changes reported for key bone markers.

Study Details

PMID:20180356
Participants:102
Impact:−22.1% at 3 months; −46.5% at 6 months
Trust score:4/5

Risedronate (daily or weekly) markedly lowered bone turnover markers (CTX and bone ALP) over 3–6 months in postmenopausal women with osteoporosis.

Trust comment: Randomized, double-blind controlled trial with adequate sample size and clear biochemical endpoints.

Study Details

PMID:19927782
Participants:102
Impact:−22.1% at 3 months; −46.5% at 6 months
Trust score:4/5

lumbar BMD

2 evidences

In elderly osteoporotic women, alendronate increased lumbar BMD and reduced bone resorption more than etidronate; both treatments reduced back pain.

Trust comment: Open-label head-to-head prospective study with small sample but clear biochemical and BMD differences.

Study Details

PMID:16385649
Participants:50
Impact:+9.3% (alendronate) vs +2.7% (etidronate) at 12 months
Trust score:3/5

Alendronate reduced pain and improved pain-related quality of life and increased lumbar BMD more than alfacalcidol in postmenopausal osteoporotic women.

Trust comment: Randomized comparative crossover but open-label and small sample, limiting robustness.

Study Details

PMID:20458350
Participants:34
Impact:increased from 0.637 to 0.659 g/cm² (P < 0.001)
Trust score:3/5

Improvement in Stamey urinary incontinence grade

1 evidences

Compared CaHA vs bovine dermal collagen injections for female stress urinary incontinence; both tolerated and showed improvement at 12 months.

Trust comment: Large randomized multicenter single-blind trial with 12-month follow-up and clear endpoints; some attrition (231/296 with 12-month data).

Study Details

PMID:17482925
Participants:231
Impact:57.0% of collagen patients improved ≥1 Stamey grade at 12 months
Trust score:4/5

Required only one injection

1 evidences

Compared CaHA vs bovine dermal collagen injections for female stress urinary incontinence; both tolerated and showed improvement at 12 months.

Trust comment: Large randomized multicenter single-blind trial with 12-month follow-up and clear endpoints; some attrition (231/296 with 12-month data).

Study Details

PMID:17482925
Participants:231
Impact:26.1% of collagen patients required only one injection during study
Trust score:4/5

Total injected volume

1 evidences

Compared CaHA vs bovine dermal collagen injections for female stress urinary incontinence; both tolerated and showed improvement at 12 months.

Trust comment: Large randomized multicenter single-blind trial with 12-month follow-up and clear endpoints; some attrition (231/296 with 12-month data).

Study Details

PMID:17482925
Participants:231
Impact:Average total volume for collagen = 6.6 mL
Trust score:4/5

Serum PTH

1 evidences

Daily high-calcium mineral water (596 mg Ca) for 6 months lowered PTH and multiple bone turnover markers; adding 400 IU vitamin D provided no additional reduction.

Trust comment: Randomized double-blind placebo-controlled trial with large completed sample and objective biochemical endpoints.

Study Details

PMID:15744450
Participants:152
Impact:-14.1% (HCaMW vs placebo)
Trust score:4/5

Root coverage at 3 years

1 evidences

Randomized trial comparing xenogenic collagen matrix vs connective tissue graft for gingival recession over 36 months; collagen matrix provided less root coverage and was not non-inferior to graft.

Trust comment: Randomized multicentre trial with 36-month follow-up and objective outcomes; non-inferiority not demonstrated for CMX.

Study Details

PMID:33817812
Participants:125
Impact:CMX = 1.5 ± 1.5 mm; CTG = 2.0 ± 1.0 mm (difference 0.32 mm, 95% CI -0.02 to 0.65)
Trust score:4/5

Stability of root coverage

1 evidences

Randomized trial comparing xenogenic collagen matrix vs connective tissue graft for gingival recession over 36 months; collagen matrix provided less root coverage and was not non-inferior to graft.

Trust comment: Randomized multicentre trial with 36-month follow-up and objective outcomes; non-inferiority not demonstrated for CMX.

Study Details

PMID:33817812
Participants:125
Impact:No differences between CMX and CTG from 6 to 36 months
Trust score:4/5

Recovery and morbidity

1 evidences

Randomized trial comparing xenogenic collagen matrix vs connective tissue graft for gingival recession over 36 months; collagen matrix provided less root coverage and was not non-inferior to graft.

Trust comment: Randomized multicentre trial with 36-month follow-up and objective outcomes; non-inferiority not demonstrated for CMX.

Study Details

PMID:33817812
Participants:125
Impact:Previously reported shorter recovery and lower morbidity for CMX (as noted by authors)
Trust score:4/5

Implant success rate

3 evidences

Immediate implants with buccal defects filled using DBBM + collagen membrane versus tuberosity bone showed similar ridge alterations, clinical parameters and patient-reported outcomes at 1 year.

Trust comment: Randomized trial but small sample (31 patients); clinically relevant outcomes and 1-year follow-up, but limited power.

Study Details

PMID:35830145
Participants:31
Impact:100% in both groups at 1 year
Trust score:3/5

Randomized clinical study of two graft materials with the same collagen barrier showed 100% implant survival and similar clinical and radiographic outcomes at 1-year post-loading.

Trust comment: Small randomized clinical study; collagen barrier was used in both arms so it does not isolate collagen effect.

Study Details

PMID:22672611
Participants:27
Impact:similar success (84.6% vs 83.3%)
Trust score:3/5

Randomized trial of equine-derived collagenated xenogeneic bone block (CXBB) versus autogenous bone block (ABB) for lateral ridge augmentation; 1-year implant survival and clinical/aesthetic outcomes showed no statistically significant differences.

Trust comment: Randomized controlled clinical study with 50 patients and 1-year follow-up; moderate quality but limited sample size for subgroup outcomes.

Study Details

PMID:37846853
Participants:50
Impact:53.6% (CXBB) vs 63.6% (ABB)
Trust score:4/5

Facial-palatal ridge thickness (FPT) change

1 evidences

Immediate implants with buccal defects filled using DBBM + collagen membrane versus tuberosity bone showed similar ridge alterations, clinical parameters and patient-reported outcomes at 1 year.

Trust comment: Randomized trial but small sample (31 patients); clinically relevant outcomes and 1-year follow-up, but limited power.

Study Details

PMID:35830145
Participants:31
Impact:No significant difference between DBBM+collagen membrane and tuberosity bone (1-year)
Trust score:3/5

Pink esthetic score

1 evidences

Immediate implants with buccal defects filled using DBBM + collagen membrane versus tuberosity bone showed similar ridge alterations, clinical parameters and patient-reported outcomes at 1 year.

Trust comment: Randomized trial but small sample (31 patients); clinically relevant outcomes and 1-year follow-up, but limited power.

Study Details

PMID:35830145
Participants:31
Impact:DBBM+collagen = 11.5 ± 1.7 (no significant difference vs tuberosity)
Trust score:3/5

corneal hysteresis (CH)

1 evidences

Randomized clinical trial measuring corneal biomechanics up to 1 year after corneal collagen cross-linking (CXL); no meaningful change in measured biomechanical indices at 1 year.

Trust comment: Prospective randomized controlled clinical trial with objective biomechanical measures but single-center and measured by ORA which may have limited sensitivity.

Study Details

PMID:21993470
Participants:69
Impact:≈+0.05 units (no significant change; P=0.78)
Trust score:4/5

time to haemostasis

2 evidences

Patients receiving PTFE vascular grafts were randomized to collagen-containing TachoComb H patches or standard compression; time to haemostasis was shorter with the patch.

Trust comment: Randomized controlled trial with a small sample but a clear, statistically significant reduction in time to haemostasis.

Study Details

PMID:15079782
Participants:24
Impact:decreased (median 300 s with TachoComb H vs 660 s control; P=0.0134)
Trust score:4/5

Randomized multicentre trial in vascular surgery showing collagen patch with fibrin components reduced time to haemostasis and local blood loss versus compresses.

Trust comment: Prospective randomized multicentre design with significant clinical endpoints, but moderate sample size.

Study Details

PMID:11052282
Participants:60
Impact:326.0 s vs 514.3 s (−188.3 s; ≈−36.6%; P=0.006)
Trust score:4/5

Intraoperative blood loss

3 evidences

Randomized multicentre trial in vascular surgery showing collagen patch with fibrin components reduced time to haemostasis and local blood loss versus compresses.

Trust comment: Prospective randomized multicentre design with significant clinical endpoints, but moderate sample size.

Study Details

PMID:11052282
Participants:60
Impact:median 24.5 g vs 57.3 g (−32.8 g; ≈−57.2%; P=0.045)
Trust score:4/5

Randomized trial comparing woven vs collagen-impregnated knitted Dacron arterial grafts; knitted grafts had lower intraoperative blood loss but otherwise similar performance and patency at 1 year.

Trust comment: Large randomized trial with 267 patients and 1-year follow-up; pragmatic surgical endpoints and statistically reported differences give moderate-high trust.

Study Details

PMID:9667705
Participants:267
Impact:knitted grafts lower by 327 ml (1690 vs 1363 ml; P=0.049)
Trust score:4/5

Using rhBMP-2 on an absorbable collagen sponge with interbody cages yielded higher fusion rates and less operative time and blood loss than autograft, avoiding donor-site morbidity.

Trust comment: Prospective randomized multicenter trial with objective radiographic endpoints; however collagen was used as a carrier for rhBMP-2, so effects cannot be attributed solely to collagen.

Study Details

PMID:12394656
Participants:279
Impact:reduced by 43.3 mL (109.8 vs 153.1 mL)
Trust score:4/5

puncture-site hemostasis time

1 evidences

Multicenter randomized trial showing a percutaneous collagen hemostasis device substantially reduced puncture-site hemostasis time and shortened time to ambulation versus manual compression, without increasing major complications.

Trust comment: Large multicenter randomized trial with clear, clinically relevant endpoints; some subgroup complexity but overall reliable.

Study Details

PMID:10745611
Participants:165
Impact:4.1 min vs 17.6 min (≈−13.5 min; ≈−76.7%; P<0.0001)
Trust score:4/5

steep keratometry (K2)

1 evidences

Observer-masked RCT in adolescents showing corneal cross-linking (CXL) substantially slowed keratoconus progression and improved keratometry and visual acuity at 18 months versus standard care.

Trust comment: Well-designed observer-masked randomized controlled trial with clinically meaningful endpoints and clear effect sizes.

Study Details

PMID:33892046
Participants:60
Impact:adjusted mean difference −3.0 D at 18 months (95% CI −4.9 to −1.1 D; P=0.002)
Trust score:5/5

keratoconus progression rate

1 evidences

Observer-masked RCT in adolescents showing corneal cross-linking (CXL) substantially slowed keratoconus progression and improved keratometry and visual acuity at 18 months versus standard care.

Trust comment: Well-designed observer-masked randomized controlled trial with clinically meaningful endpoints and clear effect sizes.

Study Details

PMID:33892046
Participants:60
Impact:CXL 7% vs standard care 43% (absolute −36 percentage points; odds ratio 0.1; P=0.004)
Trust score:5/5

visual acuity (uncorrected)

1 evidences

Observer-masked RCT in adolescents showing corneal cross-linking (CXL) substantially slowed keratoconus progression and improved keratometry and visual acuity at 18 months versus standard care.

Trust comment: Well-designed observer-masked randomized controlled trial with clinically meaningful endpoints and clear effect sizes.

Study Details

PMID:33892046
Participants:60
Impact:adjusted difference −0.31 logMAR favoring CXL (P=0.002)
Trust score:5/5

countermovement jump (CMJ) recovery

1 evidences

Small double-blind randomized trial in males: short-term collagen peptide supplementation modestly improved jump recovery and tended to reduce muscle soreness but did not affect inflammation or bone turnover markers.

Trust comment: Randomized double-blind trial but small sample (n=24) limiting power; objective measures but several null outcomes.

Study Details

PMID:30783776
Participants:24
Impact:CP 89.96% vs CON 78.67% of baseline at 48 h (≈+11.3 percentage points; P=0.050)
Trust score:3/5

bone turnover markers (β-CTX, P1NP)

1 evidences

Small double-blind randomized trial in males: short-term collagen peptide supplementation modestly improved jump recovery and tended to reduce muscle soreness but did not affect inflammation or bone turnover markers.

Trust comment: Randomized double-blind trial but small sample (n=24) limiting power; objective measures but several null outcomes.

Study Details

PMID:30783776
Participants:24
Impact:no change (P>0.05)
Trust score:3/5

Keratometry (Km)

1 evidences

Two CXL methods in progressive keratoconus were compared over 24 months; both stabilized disease but standard (epi-off) CXL produced greater corneal flattening and deeper stromal effects.

Trust comment: Randomized controlled trial with 2-year follow-up and objective measures; sample size moderate and methods clearly reported.

Study Details

PMID:27040458
Participants:119
Impact:-2.15 D (standard CXL) vs -0.97 D (transepithelial iontophoresis) over 24 months
Trust score:4/5

Demarcation line depth

1 evidences

Two CXL methods in progressive keratoconus were compared over 24 months; both stabilized disease but standard (epi-off) CXL produced greater corneal flattening and deeper stromal effects.

Trust comment: Randomized controlled trial with 2-year follow-up and objective measures; sample size moderate and methods clearly reported.

Study Details

PMID:27040458
Participants:119
Impact:Standard: ~292 ±14 μm vs Transepithelial: ~172 ±16 μm (early postoperative)
Trust score:4/5

Uncorrected and corrected visual acuity (UCVA/CDVA)

1 evidences

In pediatric keratoconus, both conventional and accelerated CXL improved vision and reduced corneal steepness with no progression over 3 years; differences were most evident at 1 year.

Trust comment: Prospective randomized contralateral-eye design in pediatric patients with 3-year follow-up; moderate sample size but robust within-patient comparison.

Study Details

PMID:29564806
Participants:34
Impact:Both UCVA and CDVA improved after CXL (accelerated group showed better mean LogMAR UCVA/CDVA at 12 months)
Trust score:4/5

Disease progression

1 evidences

In pediatric keratoconus, both conventional and accelerated CXL improved vision and reduced corneal steepness with no progression over 3 years; differences were most evident at 1 year.

Trust comment: Prospective randomized contralateral-eye design in pediatric patients with 3-year follow-up; moderate sample size but robust within-patient comparison.

Study Details

PMID:29564806
Participants:34
Impact:No keratoconus progression observed over 36 months
Trust score:4/5

MRI defect filling (≥50%)

1 evidences

Adding a porcine-derived collagen scaffold (C-ACT) to microfracture led to better MRI repair (defect filling, integration) and improved pain/function outcomes versus microfracture alone through 24 months.

Trust comment: Multicenter randomized controlled trial with objective MRI and patient-reported outcomes and adequate sample size for orthopaedic RCT.

Study Details

PMID:31785390
Participants:100
Impact:Higher odds with C-ACT at 12 months (OR 3.984; P=0.0377)
Trust score:4/5

Repaired tissue / reference cartilage (RT/RC) ratio ≥1

1 evidences

Adding a porcine-derived collagen scaffold (C-ACT) to microfracture led to better MRI repair (defect filling, integration) and improved pain/function outcomes versus microfracture alone through 24 months.

Trust comment: Multicenter randomized controlled trial with objective MRI and patient-reported outcomes and adequate sample size for orthopaedic RCT.

Study Details

PMID:31785390
Participants:100
Impact:More likely in C-ACT group (OR 11.37; P=0.0126)
Trust score:4/5

Pain improvement (VAS 20% rate) and KOOS pain MCID

1 evidences

Adding a porcine-derived collagen scaffold (C-ACT) to microfracture led to better MRI repair (defect filling, integration) and improved pain/function outcomes versus microfracture alone through 24 months.

Trust comment: Multicenter randomized controlled trial with objective MRI and patient-reported outcomes and adequate sample size for orthopaedic RCT.

Study Details

PMID:31785390
Participants:100
Impact:VAS 20% improvement OR 2.808 at 24 months; KOOS pain MCID achieved in 77.8% (C-ACT) vs 52.3% (microfracture) at 12 months (P=0.0116)
Trust score:4/5

total corneal density

1 evidences

Both accelerated and conventional corneal collagen cross-linking increased corneal density at 6 months, especially in anterior and middle layers, with no major difference between methods.

Trust comment: Small randomized study with objective densitometry outcomes but limited sample size.

Study Details

PMID:29931571
Participants:23
Impact:+ (significant increase at 6 months, P = 0.002)
Trust score:3/5

anterior corneal layer density

1 evidences

Both accelerated and conventional corneal collagen cross-linking increased corneal density at 6 months, especially in anterior and middle layers, with no major difference between methods.

Trust comment: Small randomized study with objective densitometry outcomes but limited sample size.

Study Details

PMID:29931571
Participants:23
Impact:+ (significant increase, P < 0.001)
Trust score:3/5

middle corneal layer density

1 evidences

Both accelerated and conventional corneal collagen cross-linking increased corneal density at 6 months, especially in anterior and middle layers, with no major difference between methods.

Trust comment: Small randomized study with objective densitometry outcomes but limited sample size.

Study Details

PMID:29931571
Participants:23
Impact:+ (significant increase, P = 0.035)
Trust score:3/5

myofibrillar protein synthesis rate

1 evidences

Fifteen grams hydrolyzed collagen twice daily during 1 week of intense resistance training raised some plasma collagen-related amino acids but did not increase muscle myofibrillar or connective protein synthesis rates.

Trust comment: Randomized, double-blind trial with direct biochemical measurements but small sample and short intervention.

Study Details

PMID:39086044
Participants:25
Impact:no change (no increase with collagen supplementation)
Trust score:4/5

muscle connective protein synthesis rate

1 evidences

Fifteen grams hydrolyzed collagen twice daily during 1 week of intense resistance training raised some plasma collagen-related amino acids but did not increase muscle myofibrillar or connective protein synthesis rates.

Trust comment: Randomized, double-blind trial with direct biochemical measurements but small sample and short intervention.

Study Details

PMID:39086044
Participants:25
Impact:no change (no increase with collagen supplementation)
Trust score:4/5

implant surface contact with peri-implant radiopaque area

1 evidences

At 12 months both transcrestal and lateral sinus floor elevation (latter with a resorbable collagen membrane) achieved near-complete radiographic implant embedding and minimal marginal bone loss.

Trust comment: Bi-center randomized trial with objective radiographic endpoints and one-year follow-up.

Study Details

PMID:31240743
Participants:54
Impact:median 100% contact at 12 months (no intergroup difference)
Trust score:4/5

graft maturation (radiographic)

1 evidences

At 12 months both transcrestal and lateral sinus floor elevation (latter with a resorbable collagen membrane) achieved near-complete radiographic implant embedding and minimal marginal bone loss.

Trust comment: Bi-center randomized trial with objective radiographic endpoints and one-year follow-up.

Study Details

PMID:31240743
Participants:54
Impact:radiographic aspect suggestive of advanced maturation at 12 months
Trust score:4/5

patient self-rated voice

1 evidences

Both bovine collagen injections and hylan B gel improved patients' voice and glottal closure at 12 months; collagen showed improvement but hylan B gel preserved vibration and increased phonation time more.

Trust comment: Prospective randomized trial with objective voice measures and 12-month follow-up, though some nonrandomized cases were included.

Study Details

PMID:12461343
Participants:83
Impact:+ (significant improvement at 12 months with collagen)
Trust score:4/5

glottal closure (videostroboscopy)

2 evidences

Both bovine collagen injections and hylan B gel improved patients' voice and glottal closure at 12 months; collagen showed improvement but hylan B gel preserved vibration and increased phonation time more.

Trust comment: Prospective randomized trial with objective voice measures and 12-month follow-up, though some nonrandomized cases were included.

Study Details

PMID:12461343
Participants:83
Impact:+ (significant improvement with collagen)
Trust score:4/5

Randomized trial comparing hylan B gel vs bovine cross-linked collagen injections for glottal insufficiency showed both improved voice and glottal closure; collagen showed more resorption/trend to more loss.

Trust comment: Direct randomized clinical comparison of collagen injections with moderate sample size and 2-year follow-up but with substantial dropout, limiting strength.

Study Details

PMID:15768820
Participants:70
Impact:significant improvement in both groups
Trust score:3/5

maximum phonation time

1 evidences

Both bovine collagen injections and hylan B gel improved patients' voice and glottal closure at 12 months; collagen showed improvement but hylan B gel preserved vibration and increased phonation time more.

Trust comment: Prospective randomized trial with objective voice measures and 12-month follow-up, though some nonrandomized cases were included.

Study Details

PMID:12461343
Participants:83
Impact:no significant increase for collagen group (hylan group showed significant increase)
Trust score:4/5

time to controlled bleeding

2 evidences

The collagen-based CoStasis hemostat produced higher hemostatic success and much faster bleeding control than standard manual compression across multiple surgical specialties.

Trust comment: Large randomized controlled trial with objective, clinically relevant endpoints and clear superiority signal.

Study Details

PMID:11283536
Participants:318
Impact:median 42 s (CoStasis) vs 150 s (control)
Trust score:5/5

A sprayable collagen-thrombin-plasma composite stopped diffuse liver bleeding faster and more reliably than a collagen sponge applied with pressure.

Trust comment: Multicenter randomized controlled trial with clear, clinically relevant endpoints and complete reporting of outcomes.

Study Details

PMID:11030881
Participants:67
Impact:median 62 s (experimental) vs 250 s (control)
Trust score:5/5

time to complete hemostasis

2 evidences

The collagen-based CoStasis hemostat produced higher hemostatic success and much faster bleeding control than standard manual compression across multiple surgical specialties.

Trust comment: Large randomized controlled trial with objective, clinically relevant endpoints and clear superiority signal.

Study Details

PMID:11283536
Participants:318
Impact:median 75 s (CoStasis) vs 252 s (control)
Trust score:5/5

A sprayable collagen-thrombin-plasma composite stopped diffuse liver bleeding faster and more reliably than a collagen sponge applied with pressure.

Trust comment: Multicenter randomized controlled trial with clear, clinically relevant endpoints and complete reporting of outcomes.

Study Details

PMID:11030881
Participants:67
Impact:median 150 s (experimental) vs 360 s (control)
Trust score:5/5

ipsilateral stroke incidence

1 evidences

In this randomized trial, PTFE patching had fewer ipsilateral strokes and less late recurrent stenosis than collagen-impregnated Dacron (Hemashield).

Trust comment: Randomized trial with substantial follow-up and clear outcome measures; moderate-high quality though follow-up mean 26 months.

Study Details

PMID:12796586
Participants:180
Impact:Hemashield 8% (all ipsilateral strokes) vs PTFE 0% (higher with Hemashield)
Trust score:4/5

freedom from >=70% recurrent stenosis (36 months)

1 evidences

In this randomized trial, PTFE patching had fewer ipsilateral strokes and less late recurrent stenosis than collagen-impregnated Dacron (Hemashield).

Trust comment: Randomized trial with substantial follow-up and clear outcome measures; moderate-high quality though follow-up mean 26 months.

Study Details

PMID:12796586
Participants:180
Impact:Hemashield 78% vs PTFE 100% (higher recurrent stenosis with Hemashield; multivariate significant)
Trust score:4/5

stroke-free survival (36 months)

1 evidences

In this randomized trial, PTFE patching had fewer ipsilateral strokes and less late recurrent stenosis than collagen-impregnated Dacron (Hemashield).

Trust comment: Randomized trial with substantial follow-up and clear outcome measures; moderate-high quality though follow-up mean 26 months.

Study Details

PMID:12796586
Participants:180
Impact:Hemashield 89% vs PTFE 100% (lower stroke-free survival with Hemashield)
Trust score:4/5

peri-implant marginal bone loss (PBL)

1 evidences

At 1 year, titanium meshes plus collagen membranes and reinforced PTFE membranes showed similar peri-implant bone loss and stable hard/soft tissues.

Trust comment: Randomized clinical trial with reported completion data (30 patients) and objective measures, rated as good quality for surgical device comparison.

Study Details

PMID:33017060
Participants:30
Impact:mean marginal bone loss: Group A 0.67 mm vs Group B 0.61 mm; no significant difference
Trust score:4/5

change in PBL from baseline to 1 year

1 evidences

At 1 year, titanium meshes plus collagen membranes and reinforced PTFE membranes showed similar peri-implant bone loss and stable hard/soft tissues.

Trust comment: Randomized clinical trial with reported completion data (30 patients) and objective measures, rated as good quality for surgical device comparison.

Study Details

PMID:33017060
Participants:30
Impact:overall change 0.12 to 0.76 mm
Trust score:4/5

hard and soft tissue stability

1 evidences

At 1 year, titanium meshes plus collagen membranes and reinforced PTFE membranes showed similar peri-implant bone loss and stable hard/soft tissues.

Trust comment: Randomized clinical trial with reported completion data (30 patients) and objective measures, rated as good quality for surgical device comparison.

Study Details

PMID:33017060
Participants:30
Impact:stable in both groups with <1.0 mm bone loss in first year
Trust score:4/5

compression time

1 evidences

Topical collagen sealing after femoral artery access reduced compression time, shortened bedrest, and lowered bleeding rates versus pressure dressing.

Trust comment: Randomized trial in 100 patients with clear clinically relevant endpoints and statistically significant differences.

Study Details

PMID:10745612
Participants:100
Impact:collagen 4.3 min vs pressure dressing 42.3 min (≈ −38 min)
Trust score:4/5

bleeding/large hematoma incidence

1 evidences

Topical collagen sealing after femoral artery access reduced compression time, shortened bedrest, and lowered bleeding rates versus pressure dressing.

Trust comment: Randomized trial in 100 patients with clear clinically relevant endpoints and statistically significant differences.

Study Details

PMID:10745612
Participants:100
Impact:collagen 4/50 (8%) vs pressure 11/50 (22%) (lower with collagen, P < 0.05)
Trust score:4/5

duration of bedrest

1 evidences

Topical collagen sealing after femoral artery access reduced compression time, shortened bedrest, and lowered bleeding rates versus pressure dressing.

Trust comment: Randomized trial in 100 patients with clear clinically relevant endpoints and statistically significant differences.

Study Details

PMID:10745612
Participants:100
Impact:reduced with collagen (earlier ambulation reported)
Trust score:4/5

index of surface variance (ISV)

1 evidences

One year after corneal collagen crosslinking, several corneal shape indices improved significantly, indicating improved corneal shape though visual acuity changes did not correlate.

Trust comment: Prospective clinical trial with 1-year follow-up and objective topographic measures; good quality though correlation with vision was absent.

Study Details

PMID:21700105
Participants:71
Impact:significant improvement at 1 year (P < .001)
Trust score:4/5

index of vertical asymmetry (IVA)

1 evidences

One year after corneal collagen crosslinking, several corneal shape indices improved significantly, indicating improved corneal shape though visual acuity changes did not correlate.

Trust comment: Prospective clinical trial with 1-year follow-up and objective topographic measures; good quality though correlation with vision was absent.

Study Details

PMID:21700105
Participants:71
Impact:significant improvement at 1 year (P < .001)
Trust score:4/5

keratoconus index (KI) and minimum radius of curvature (Rmin)

1 evidences

One year after corneal collagen crosslinking, several corneal shape indices improved significantly, indicating improved corneal shape though visual acuity changes did not correlate.

Trust comment: Prospective clinical trial with 1-year follow-up and objective topographic measures; good quality though correlation with vision was absent.

Study Details

PMID:21700105
Participants:71
Impact:significant improvement at 1 year (P < .001)
Trust score:4/5

clinical attachment level gain

3 evidences

Collagen membranes (native vs ribosome-crosslinked) gave similar clinical improvements in periodontal defect regeneration at 6 months.

Trust comment: Randomized clinical trial with objective periodontal endpoints and adequate sample size, 6-month follow-up.

Study Details

PMID:38962931
Participants:80
Impact:NCM +3.1 ±1.5 mm; RCCM +2.9 ±1.5 mm (no significant difference)
Trust score:4/5

Use of a dual anti-collagen membrane for guided tissue regeneration produced greater 1-year clinical attachment gains and bone density increases than an atelocollagen membrane; results were stable to 6 years.

Trust comment: Randomized clinical trial but very small number of patients/teeth limits external validity despite long-term follow-up.

Study Details

PMID:21163010
Participants:24
Impact:Gain 3.93 ± 1.74 mm (dual membrane) vs 2.25 ± 1.90 mm (atelocollagen) at 1 year (P=0.044)
Trust score:3/5

Using a collagen membrane with bone graft produced similar tooth-supporting tissue gain as the alternative treatment over 12 months.

Trust comment: Randomized allocation with 12-month follow-up and objective clinical endpoints, but modest sample size limits precision.

Study Details

PMID:24835417
Participants:40
Impact:EMD+DBBM +3.8 mm vs CM+DBBM +3.7 mm (no significant difference)
Trust score:4/5

bone fill percentage

1 evidences

Collagen membranes (native vs ribosome-crosslinked) gave similar clinical improvements in periodontal defect regeneration at 6 months.

Trust comment: Randomized clinical trial with objective periodontal endpoints and adequate sample size, 6-month follow-up.

Study Details

PMID:38962931
Participants:80
Impact:NCM 102.3 ±53.5%; RCCM 92.3 ±40.1% (p>0.05)
Trust score:4/5

ulcer area

1 evidences

Topical collagen biomaterial (Collost) plus standard care produced greater wound area reduction and higher rates of epithelialization vs standard therapy over 4 weeks.

Trust comment: Multicenter randomized trial showing clear wound-area and healing advantages for topical collagen, though follow-up was short (4 weeks).

Study Details

PMID:29953106
Participants:75
Impact:Collost: 13.5 → 2.1 cm²; control: 12.5 → 7.0 cm² (greater reduction with Collost)
Trust score:4/5

complete epithelialization rate

1 evidences

Topical collagen biomaterial (Collost) plus standard care produced greater wound area reduction and higher rates of epithelialization vs standard therapy over 4 weeks.

Trust comment: Multicenter randomized trial showing clear wound-area and healing advantages for topical collagen, though follow-up was short (4 weeks).

Study Details

PMID:29953106
Participants:75
Impact:Collost 21.1% vs control 14.7% at 4 weeks
Trust score:4/5

ineffective treatment frequency

1 evidences

Topical collagen biomaterial (Collost) plus standard care produced greater wound area reduction and higher rates of epithelialization vs standard therapy over 4 weeks.

Trust comment: Multicenter randomized trial showing clear wound-area and healing advantages for topical collagen, though follow-up was short (4 weeks).

Study Details

PMID:29953106
Participants:75
Impact:Collost 7.9% vs control 32.4% (fewer ineffective outcomes)
Trust score:4/5

marginal bone level change

1 evidences

ARP using collagen-containing DBBM-C and collagen matrix did not change 1-year marginal bone loss compared with natural healing but had more early soft-tissue exposure.

Trust comment: Randomized trial but small completed sample (22) and primary endpoint non-significant; objective measures reported.

Study Details

PMID:38807310
Participants:22
Impact:Treatment 2.09 ±1.03 mm vs control 1.58 ±0.73 mm (p=0.339; no significant difference)
Trust score:3/5

early soft-tissue exposure

1 evidences

ARP using collagen-containing DBBM-C and collagen matrix did not change 1-year marginal bone loss compared with natural healing but had more early soft-tissue exposure.

Trust comment: Randomized trial but small completed sample (22) and primary endpoint non-significant; objective measures reported.

Study Details

PMID:38807310
Participants:22
Impact:Test 33% vs control 0% (p=0.047; increased exposure in ARP group)
Trust score:3/5

soft tissue recession

1 evidences

ARP using collagen-containing DBBM-C and collagen matrix did not change 1-year marginal bone loss compared with natural healing but had more early soft-tissue exposure.

Trust comment: Randomized trial but small completed sample (22) and primary endpoint non-significant; objective measures reported.

Study Details

PMID:38807310
Participants:22
Impact:Control mean recession 0.36 ±0.84 mm; test group no recession observed (p=0.2)
Trust score:3/5

alveolar width

1 evidences

Multicentre RCT comparing dPTFE vs collagen membrane for lateral bone augmentation at anterior maxilla; similar alveolar width outcomes but higher infection with dPTFE.

Trust comment: Randomized multicentre trial with complete 1-year follow-up; small sample size but appropriate design and clear infection signal.

Study Details

PMID:40298001
Participants:36
Impact:no significant difference; estimated mean difference 0.65 mm (95% CI -0.82 to 2.12), p=0.381
Trust score:4/5

implant integration / marginal bone loss

1 evidences

Multicentre RCT comparing dPTFE vs collagen membrane for lateral bone augmentation at anterior maxilla; similar alveolar width outcomes but higher infection with dPTFE.

Trust comment: Randomized multicentre trial with complete 1-year follow-up; small sample size but appropriate design and clear infection signal.

Study Details

PMID:40298001
Participants:36
Impact:implants integrated uneventfully with minimal marginal bone loss (no numeric values)
Trust score:4/5

maximum keratometric reading (Kmax)

1 evidences

In keratoconus patients, both conventional and accelerated corneal collagen cross-linking using methylcellulose-riboflavin improved visual acuity and maximum keratometry at 2 years with no difference between protocols.

Trust comment: Prospective randomized clinical trial with 2-year follow-up and objective ophthalmologic endpoints, but moderate sample size.

Study Details

PMID:30365412
Participants:40
Impact:statistically significant improvement vs baseline in both groups at 2 years
Trust score:4/5

dermal collagen amount

1 evidences

Low-dose oral isotretinoin given thrice weekly for 3 months increased dermal collagen content and improved clinical signs of photoaging in women.

Trust comment: Randomized small clinical study with objective histologic measures but no placebo control and limited sample size.

Study Details

PMID:18811602
Participants:30
Impact:significant increase (10 mg: mean 37.8%→44.4%, p=0.029; 20 mg: mean 36.6%→41.9%, p=0.01)
Trust score:3/5

elastic fiber amount

1 evidences

Low-dose oral isotretinoin given thrice weekly for 3 months increased dermal collagen content and improved clinical signs of photoaging in women.

Trust comment: Randomized small clinical study with objective histologic measures but no placebo control and limited sample size.

Study Details

PMID:18811602
Participants:30
Impact:trend toward decrease (10 mg: 15.3%→12.0%, p=0.014; 20 mg: 15.5%→14.0%, p=0.125)
Trust score:3/5

clinical skin appearance (texture, wrinkles, color)

1 evidences

Low-dose oral isotretinoin given thrice weekly for 3 months increased dermal collagen content and improved clinical signs of photoaging in women.

Trust comment: Randomized small clinical study with objective histologic measures but no placebo control and limited sample size.

Study Details

PMID:18811602
Participants:30
Impact:reported improvement by physicians and patients
Trust score:3/5

rate of sufficient bone regeneration for implant restoration

1 evidences

In patients needing large vertical maxillary augmentation, composite grafts containing rhBMP-2 on an acellular collagen sponge performed similarly to 100% autogenous grafts with slightly more viable new bone and less donor-site morbidity.

Trust comment: Randomized open-label clinical trial with histologic endpoints and moderate sample size; some graft losses reported but overall robust comparison.

Study Details

PMID:24066341
Participants:40
Impact:autogenous 18/18 (100%); composite grafts 17/18 (97.4%) after early losses
Trust score:4/5

viable new bone fraction (histology)

1 evidences

In patients needing large vertical maxillary augmentation, composite grafts containing rhBMP-2 on an acellular collagen sponge performed similarly to 100% autogenous grafts with slightly more viable new bone and less donor-site morbidity.

Trust comment: Randomized open-label clinical trial with histologic endpoints and moderate sample size; some graft losses reported but overall robust comparison.

Study Details

PMID:24066341
Participants:40
Impact:composite grafts 59% ± 12% vs autogenous grafts 54% ± 10% viable new bone
Trust score:4/5

surgical morbidity

1 evidences

In patients needing large vertical maxillary augmentation, composite grafts containing rhBMP-2 on an acellular collagen sponge performed similarly to 100% autogenous grafts with slightly more viable new bone and less donor-site morbidity.

Trust comment: Randomized open-label clinical trial with histologic endpoints and moderate sample size; some graft losses reported but overall robust comparison.

Study Details

PMID:24066341
Participants:40
Impact:composite grafts associated with less blood loss and shorter surgical time but greater/longer edema
Trust score:4/5

keratinized tissue width

4 evidences

Using two types of xenogeneic collagen matrices with bone graft helped maintain soft tissues and limited ridge resorption after tooth extraction, with small increases in gingival thickness.

Trust comment: Randomized controlled prospective study but very small completed sample (n=23), reducing precision and external validity.

Study Details

PMID:26745614
Participants:23
Impact:−0.5 mm (decrease) after healing
Trust score:3/5

A xenogeneic collagen matrix worked as well as connective tissue graft to produce keratinized gum tissue and patients reported less pain and shorter surgery time.

Trust comment: Randomized controlled trial with objective clinical measures but small sample (n=24) limits precision.

Study Details

PMID:22092380
Participants:24
Impact:2.8 mm at 6 months (CM); 2.75 mm at 6 months (CTG); inter-group difference not significant
Trust score:4/5

Adding a xenogeneic collagen matrix to coronally advanced flap surgery increased keratinized tissue width and gingival thickness vs flap alone, while root coverage and patient satisfaction were similar at 12 months.

Trust comment: Randomized controlled trial with 45 patients and objective clinical measures; moderate sample size limits power for some outcomes.

Study Details

PMID:27717210
Participants:45
Impact:+1.05 mm (test: 1.97 → 3.02 mm) vs +0.64 mm (control: 2.00 → 2.64 mm); p=0.0413
Trust score:4/5

Adding i-PRF to autogenous demineralized dentin graft did not change alveolar ridge width loss but reduced patient-reported pain and better preserved keratinized tissue at 6 months.

Trust comment: Randomized clinical trial with objective radiographic and histologic outcomes; modest sample size and partial blinding.

Study Details

PMID:39429193
Participants:22
Impact:better preserved with i-PRF (mean reduction 0.12 mm vs 0.58 mm; p=0.008)
Trust score:4/5

vestibular depth

1 evidences

A xenogeneic collagen matrix worked as well as connective tissue graft to produce keratinized gum tissue and patients reported less pain and shorter surgery time.

Trust comment: Randomized controlled trial with objective clinical measures but small sample (n=24) limits precision.

Study Details

PMID:22092380
Participants:24
Impact:increased from 2.2 to 5.1 mm at 6 months (+2.9 mm)
Trust score:4/5

patient-reported pain

1 evidences

A xenogeneic collagen matrix worked as well as connective tissue graft to produce keratinized gum tissue and patients reported less pain and shorter surgery time.

Trust comment: Randomized controlled trial with objective clinical measures but small sample (n=24) limits precision.

Study Details

PMID:22092380
Participants:24
Impact:decrease (less pain reported with CM; not statistically significant)
Trust score:4/5

wound healing time

2 evidences

Placing a gentamicin-containing collagen sponge into the wound after pilonidal sinus surgery sped healing and reduced infections and recurrences compared with oral antibiotics alone.

Trust comment: Prospective randomized study with clearly reported clinical outcomes and adequate sample size (80), though numeric effect sizes not provided for each outcome in the text.

Study Details

PMID:20819439
Participants:80
Impact:shorter mean healing time (significant)
Trust score:4/5

A matrix therapy agent (RGTA) after corneal collagen cross-linking sped corneal epithelial wound healing compared with hyaluronic acid drops.

Trust comment: Double-masked randomized trial with objective OCT and photographic measures and significant differences; moderate sample size.

Study Details

PMID:27584715
Participants:40
Impact:4.4 vs 6.1 days (mean difference 1.7 days faster with RGTA; P = .008)
Trust score:4/5

defect size (OCT)

1 evidences

A matrix therapy agent (RGTA) after corneal collagen cross-linking sped corneal epithelial wound healing compared with hyaluronic acid drops.

Trust comment: Double-masked randomized trial with objective OCT and photographic measures and significant differences; moderate sample size.

Study Details

PMID:27584715
Participants:40
Impact:12.4 vs 23.9 mm² (mean difference 11.6 mm² smaller with RGTA; P = .045)
Trust score:4/5

elastic fiber density

1 evidences

Adding cross-linked hyaluronic acid to connective tissue grafts did not change root coverage but increased elastic fibers and produced a modest (non-significant) increase in collagen density.

Trust comment: Randomized split-mouth RCT with histologic and clinical endpoints but small sample and primary intervention was hyaluronic acid rather than a collagen product.

Study Details

PMID:38808976
Participants:24
Impact:increase; statistically significant (P = 0.0419)
Trust score:3/5

collagen fiber density

2 evidences

Adding cross-linked hyaluronic acid to connective tissue grafts did not change root coverage but increased elastic fibers and produced a modest (non-significant) increase in collagen density.

Trust comment: Randomized split-mouth RCT with histologic and clinical endpoints but small sample and primary intervention was hyaluronic acid rather than a collagen product.

Study Details

PMID:38808976
Participants:24
Impact:moderate increase; not statistically significant (P = 0.300)
Trust score:3/5

Randomized triple-blind trial: plasma (argon) cleaning of titanium abutments increased cell-covered area, altered collagen fiber density/orientation, and reduced contamination versus untreated abutments.

Trust comment: Triple-blinded RCT with objective histology but small sample and some outcomes only trend-level significant.

Study Details

PMID:27552929
Participants:30
Impact:increased in plasma group (significant in internal area, P<0.05)
Trust score:3/5

periprosthetic bone mineral density (BMD)

1 evidences

Alendronate prevented periprosthetic BMD loss around femoral implants and reduced serum N-terminal telopeptides of type-1 collagen; alfacalcidol preserved lumbar spine BMD but did not prevent periprosthetic loss.

Trust comment: Human clinical study with clear BMD and collagen turnover markers; relevant to collagen metabolism but not an intervention using collagen itself.

Study Details

PMID:21776573
Participants:60
Impact:Alendronate maintained BMD in all regions; alfacalcidol did not prevent periprosthetic loss (Region 7 deficits persisted in some groups)
Trust score:3/5

serum alkaline phosphatase

1 evidences

Low-dose cyclical gallium nitrate reduced serum alkaline phosphatase and urinary markers of collagen turnover at higher doses in Paget's disease.

Trust comment: Pilot multicenter trial with clear dose-response biochemical effects but limited duration and heterogeneous prior therapies in participants.

Study Details

PMID:7852526
Participants:49
Impact:+0.5% (0.05 mg/kg) / -24% (0.25 mg/kg) / -31% (0.5 mg/kg) at 12 weeks
Trust score:3/5

collagen volume fraction (CVF)

1 evidences

Losartan reduced myocardial collagen content and serum PIP compared with amlodipine, suggesting inhibition of collagen type I synthesis and regression of myocardial fibrosis.

Trust comment: Randomized study with biopsy-proven fibrosis and correlated serum biomarker, but small sample and some dropouts limit generalizability.

Study Details

PMID:11457746
Participants:30
Impact:decreased from 5.65%±2.03% to 3.96%±1.46% in losartan-treated patients (P < 0.01)
Trust score:4/5

serum carboxy-terminal propeptide of procollagen type I (PIP)

1 evidences

Losartan reduced myocardial collagen content and serum PIP compared with amlodipine, suggesting inhibition of collagen type I synthesis and regression of myocardial fibrosis.

Trust comment: Randomized study with biopsy-proven fibrosis and correlated serum biomarker, but small sample and some dropouts limit generalizability.

Study Details

PMID:11457746
Participants:30
Impact:decreased from 127±30 to 99±26 µg/L in losartan group (P < 0.01)
Trust score:4/5

blood pressure control

1 evidences

Losartan reduced myocardial collagen content and serum PIP compared with amlodipine, suggesting inhibition of collagen type I synthesis and regression of myocardial fibrosis.

Trust comment: Randomized study with biopsy-proven fibrosis and correlated serum biomarker, but small sample and some dropouts limit generalizability.

Study Details

PMID:11457746
Participants:30
Impact:time-course changes in blood pressure were similar between groups (no difference)
Trust score:4/5

hypertensive phase incidence

1 evidences

In a randomized multicenter trial, adding an Ologen collagen matrix to Ahmed valve surgery did not improve IOP control, medication need, hypertensive phase incidence, or 1-year success compared with standard surgery.

Trust comment: Randomized multicenter clinical trial in humans with clear outcomes, but relatively small sample and only 1-year follow-up limiting power for small differences.

Study Details

PMID:30816124
Participants:56
Impact:55% in Ologen group vs 56% in control (no significant difference, p=0.947)
Trust score:4/5

success rate at 1 year

1 evidences

In a randomized multicenter trial, adding an Ologen collagen matrix to Ahmed valve surgery did not improve IOP control, medication need, hypertensive phase incidence, or 1-year success compared with standard surgery.

Trust comment: Randomized multicenter clinical trial in humans with clear outcomes, but relatively small sample and only 1-year follow-up limiting power for small differences.

Study Details

PMID:30816124
Participants:56
Impact:Ologen 69.2% vs control 76.7% (no significant difference, Log Rank p=0.531)
Trust score:4/5

Visual acuity

3 evidences

Accelerated and standard corneal collagen crosslinking produced similar 6-month outcomes for keratoconus (visual acuity, refraction, topography); central corneal thickness was higher in the standard group.

Trust comment: Prospective randomized clinical trial with 62 eyes (31 patients) and 6-month follow-up; well-designed but short-term.

Study Details

PMID:25804580
Participants:31
Impact:no significant difference between accelerated and standard groups at 6 months (uncorrected and corrected distance VA)
Trust score:4/5

Collagen cross-linking provided short-term symptomatic relief, reduced central corneal thickness and caused anterior stromal compaction in PBK patients.

Trust comment: Prospective interventional study with objective measures but small sample and limited duration of effect.

Study Details

PMID:23953101
Participants:24
Impact:improved at 1 month (from 1.925 to 1.75, P=0.010)
Trust score:3/5

Randomized study of nonpenetrating deep sclerectomy with a collagen implant, comparing adjunctive mitomycin C versus no MMC in glaucoma patients.

Trust comment: Small randomized trial (n=26) with 24-month follow-up but limited sample size reduces generalizability.

Study Details

PMID:14750756
Participants:26
Impact:unchanged throughout follow-up
Trust score:3/5

corneal curvature (Kmax / mean K)

1 evidences

Accelerated and standard corneal collagen crosslinking produced similar 6-month outcomes for keratoconus (visual acuity, refraction, topography); central corneal thickness was higher in the standard group.

Trust comment: Prospective randomized clinical trial with 62 eyes (31 patients) and 6-month follow-up; well-designed but short-term.

Study Details

PMID:25804580
Participants:31
Impact:no significant difference in changes between groups at 6 months
Trust score:4/5

objective recurrence rate

1 evidences

Randomized study comparing porcine collagen graft (Pelvicol) vs conventional repair showed no improvement in POP-Q stage at 12 months despite slightly better Ba point improvement with graft.

Trust comment: Randomized prospective controlled human study with 12-month follow-up; moderate sample size limits longer-term conclusions.

Study Details

PMID:20165833
Participants:61
Impact:control 15% (4/31) vs Pelvicol graft 7% (2/30) at 12 months
Trust score:4/5

Ba point improvement

1 evidences

Randomized study comparing porcine collagen graft (Pelvicol) vs conventional repair showed no improvement in POP-Q stage at 12 months despite slightly better Ba point improvement with graft.

Trust comment: Randomized prospective controlled human study with 12-month follow-up; moderate sample size limits longer-term conclusions.

Study Details

PMID:20165833
Participants:61
Impact:mean improvement control 6.0 cm vs graft 7.0 cm (p < 0.05) at 3 and 12 months
Trust score:4/5

POP-Q stage

1 evidences

Randomized study comparing porcine collagen graft (Pelvicol) vs conventional repair showed no improvement in POP-Q stage at 12 months despite slightly better Ba point improvement with graft.

Trust comment: Randomized prospective controlled human study with 12-month follow-up; moderate sample size limits longer-term conclusions.

Study Details

PMID:20165833
Participants:61
Impact:no overall improvement in POP-Q stage with Pelvicol graft
Trust score:4/5

probing depth reduction (buccal)

1 evidences

Adding a collagen-enriched bovine-derived xenograft to M-MIST improved probing depth reduction, clinical attachment gain and radiographic bone volume at 2 years versus M-MIST alone.

Trust comment: Randomized controlled trial with 2-year follow-up and objective clinical/radiographic endpoints but modest sample size.

Study Details

PMID:40386833
Participants:38
Impact:+~1.0 mm more reduction (3.95 ±1.39 mm vs 2.95 ±1.51 mm; p=0.041)
Trust score:4/5

clinical attachment level gain (buccal)

1 evidences

Adding a collagen-enriched bovine-derived xenograft to M-MIST improved probing depth reduction, clinical attachment gain and radiographic bone volume at 2 years versus M-MIST alone.

Trust comment: Randomized controlled trial with 2-year follow-up and objective clinical/radiographic endpoints but modest sample size.

Study Details

PMID:40386833
Participants:38
Impact:+~1.05 mm more gain (3.58 mm vs 2.53 mm; p=0.043)
Trust score:4/5

radiographic bone volume gain

1 evidences

Adding a collagen-enriched bovine-derived xenograft to M-MIST improved probing depth reduction, clinical attachment gain and radiographic bone volume at 2 years versus M-MIST alone.

Trust comment: Randomized controlled trial with 2-year follow-up and objective clinical/radiographic endpoints but modest sample size.

Study Details

PMID:40386833
Participants:38
Impact:+9.14 mm^3 more (17.77 ±11.44 mm^3 vs 8.63 ±7.10 mm^3; p=0.011)
Trust score:4/5

duration of surgery

1 evidences

In 40 patients undergoing sinus augmentation, covering the lateral window with a collagen membrane produced comparable bone formation, surgical outcomes, and patient discomfort to bony wall repositioning.

Trust comment: Prospective randomized clinical and histological study with complete clinical follow-up but loss of 11/40 biopsies for histology.

Study Details

PMID:35593928
Participants:40
Impact:45.8 ± 11.3 min (bony wall) vs 49.2 ± 11.3 min (collagen membrane); no significant difference
Trust score:4/5

drain duration

1 evidences

No statistically significant differences were found between Alloderm-RTU and DermACELL in drain duration or rates of minor/major complications in immediate subpectoral implant-based breast reconstruction.

Trust comment: Prospective randomized trial with objective outcomes though single-center, open-label design and modest enrollment limit generalizability.

Study Details

PMID:33704185
Participants:59
Impact:no significant difference (10.8 days vs 9.2 days; p=0.16)
Trust score:4/5

minor complication rate

1 evidences

No statistically significant differences were found between Alloderm-RTU and DermACELL in drain duration or rates of minor/major complications in immediate subpectoral implant-based breast reconstruction.

Trust comment: Prospective randomized trial with objective outcomes though single-center, open-label design and modest enrollment limit generalizability.

Study Details

PMID:33704185
Participants:59
Impact:no significant difference (36.8% vs 32.5%; p=0.57)
Trust score:4/5

major complication rate (reoperation)

1 evidences

No statistically significant differences were found between Alloderm-RTU and DermACELL in drain duration or rates of minor/major complications in immediate subpectoral implant-based breast reconstruction.

Trust comment: Prospective randomized trial with objective outcomes though single-center, open-label design and modest enrollment limit generalizability.

Study Details

PMID:33704185
Participants:59
Impact:no significant difference (15.8% vs 7.5%; p=0.30)
Trust score:4/5

primary composite endpoint risk (per 10 μg/L PICP)

1 evidences

Higher peripheral collagen turnover markers were associated with increased composite death/hospitalization in univariable analyses but were not independent predictors in multivariable models.

Trust comment: Well-sized biomarker substudy nested in a clinical trial, but associations did not remain after multivariable adjustment.

Study Details

PMID:21750125
Participants:334
Impact:HR 1.09 per 10 μg/L increase (95% CI 1.052–1.13; P<0.0001)
Trust score:3/5

osteopontin (per 10 nmol/L)

1 evidences

Higher peripheral collagen turnover markers were associated with increased composite death/hospitalization in univariable analyses but were not independent predictors in multivariable models.

Trust comment: Well-sized biomarker substudy nested in a clinical trial, but associations did not remain after multivariable adjustment.

Study Details

PMID:21750125
Participants:334
Impact:HR 1.084 per 10 nmol/L increase (95% CI 1.026–1.15; P=0.004)
Trust score:3/5

PIIINP (per 10 μg/L)

1 evidences

Higher peripheral collagen turnover markers were associated with increased composite death/hospitalization in univariable analyses but were not independent predictors in multivariable models.

Trust comment: Well-sized biomarker substudy nested in a clinical trial, but associations did not remain after multivariable adjustment.

Study Details

PMID:21750125
Participants:334
Impact:HR 2.47 per 10 μg/L (95% CI 0.97–6.33; P=0.059, borderline)
Trust score:3/5

complete success rate (6 months)

1 evidences

Trabeculectomy with porcine Ologen collagen implant produced similar overall success rates to MMC-augmented trabeculectomy, with comparable IOP control but more transient hyphema in the Ologen group.

Trust comment: Prospective randomized pilot study but small sample size, pilot design and ~50% loss to follow-up at 2 years limit reliability.

Study Details

PMID:23571259
Participants:28
Impact:no significant difference (100% vs 93.8%; p>0.5)
Trust score:3/5

IOP at 6 months

1 evidences

Trabeculectomy with porcine Ologen collagen implant produced similar overall success rates to MMC-augmented trabeculectomy, with comparable IOP control but more transient hyphema in the Ologen group.

Trust comment: Prospective randomized pilot study but small sample size, pilot design and ~50% loss to follow-up at 2 years limit reliability.

Study Details

PMID:23571259
Participants:28
Impact:MMC lower at 6 months (statistically significant, p=0.01)
Trust score:3/5

hyphema incidence

1 evidences

Trabeculectomy with porcine Ologen collagen implant produced similar overall success rates to MMC-augmented trabeculectomy, with comparable IOP control but more transient hyphema in the Ologen group.

Trust comment: Prospective randomized pilot study but small sample size, pilot design and ~50% loss to follow-up at 2 years limit reliability.

Study Details

PMID:23571259
Participants:28
Impact:higher in Ologen group (significant increase among early complications)
Trust score:3/5

≥50% reduction in leakage/incontinence episodes

1 evidences

Collagen gel injections reduced urinary leakage and incontinence in women with stress urinary incontinence with similar efficacy to a hydrogel at 12 months.

Trust comment: Large multicenter randomized single-blind trial with objective and subjective outcomes and 1-year follow-up; comparator-controlled.

Study Details

PMID:24704117
Participants:345
Impact:55.4% of collagen patients achieved ≥50% decrease at 12 months
Trust score:4/5

Zero stress incontinence episodes

1 evidences

Collagen gel injections reduced urinary leakage and incontinence in women with stress urinary incontinence with similar efficacy to a hydrogel at 12 months.

Trust comment: Large multicenter randomized single-blind trial with objective and subjective outcomes and 1-year follow-up; comparator-controlled.

Study Details

PMID:24704117
Participants:345
Impact:50% of collagen patients had zero episodes at 12 months
Trust score:4/5

Patient-reported cured or improved

1 evidences

Collagen gel injections reduced urinary leakage and incontinence in women with stress urinary incontinence with similar efficacy to a hydrogel at 12 months.

Trust comment: Large multicenter randomized single-blind trial with objective and subjective outcomes and 1-year follow-up; comparator-controlled.

Study Details

PMID:24704117
Participants:345
Impact:70% of collagen patients reported cured or improved
Trust score:4/5

Dimensional bone changes (height/width)

1 evidences

Adding 10% collagen to deproteinized bovine bone mineral produced similar dimensional and histological outcomes to the material without collagen after 5 months.

Trust comment: Randomized clinical trial but small sample size (22 sites) and short follow-up; outcomes are radiographic/histologic surrogates.

Study Details

PMID:27335267
Participants:22
Impact:No statistically significant difference between DBBM and DBBM-C
Trust score:3/5

Histological composition (new bone / connective tissue / residual graft)

1 evidences

Adding 10% collagen to deproteinized bovine bone mineral produced similar dimensional and histological outcomes to the material without collagen after 5 months.

Trust comment: Randomized clinical trial but small sample size (22 sites) and short follow-up; outcomes are radiographic/histologic surrogates.

Study Details

PMID:27335267
Participants:22
Impact:No significant difference between groups
Trust score:3/5

Deployment success rate (Angio-Seal)

1 evidences

An anchor-collagen based closure device (Angio-Seal) had high deployment success, low vascular complications, and reduced nursing time compared with manual compression.

Trust comment: Large consecutive-patient comparison but not fully randomized; clinically relevant endpoints reported.

Study Details

PMID:16261778
Participants:463
Impact:98% success
Trust score:3/5

Vascular complications (Angio-Seal)

1 evidences

An anchor-collagen based closure device (Angio-Seal) had high deployment success, low vascular complications, and reduced nursing time compared with manual compression.

Trust comment: Large consecutive-patient comparison but not fully randomized; clinically relevant endpoints reported.

Study Details

PMID:16261778
Participants:463
Impact:4.0% of patients
Trust score:3/5

Nursing time for access management (Angio-Seal)

1 evidences

An anchor-collagen based closure device (Angio-Seal) had high deployment success, low vascular complications, and reduced nursing time compared with manual compression.

Trust comment: Large consecutive-patient comparison but not fully randomized; clinically relevant endpoints reported.

Study Details

PMID:16261778
Participants:463
Impact:9.9 minutes
Trust score:3/5

Maximum keratometry (K-max)

1 evidences

Corneal collagen cross-linking slowed or halted keratoconus progression in treated eyes versus the untreated contralateral eyes at 1 year.

Trust comment: Prospective randomized contralateral-eye design with complete 1-year data for 26 patients, but modest sample size and some loss to follow-up.

Study Details

PMID:26180474
Participants:26
Impact:Treated: −0.22 D; Control: +0.41 D (between-group difference P=0.002)
Trust score:4/5

Proportion with >0.5 D K-max decrease

1 evidences

Corneal collagen cross-linking slowed or halted keratoconus progression in treated eyes versus the untreated contralateral eyes at 1 year.

Trust comment: Prospective randomized contralateral-eye design with complete 1-year data for 26 patients, but modest sample size and some loss to follow-up.

Study Details

PMID:26180474
Participants:26
Impact:>20% of treated eyes had >0.5 D decrease
Trust score:4/5

Treatment failure rate

1 evidences

Corneal collagen cross-linking slowed or halted keratoconus progression in treated eyes versus the untreated contralateral eyes at 1 year.

Trust comment: Prospective randomized contralateral-eye design with complete 1-year data for 26 patients, but modest sample size and some loss to follow-up.

Study Details

PMID:26180474
Participants:26
Impact:12% of treated eyes classified as failed (>0.5 D increase)
Trust score:4/5

Tomographic dimensional changes (ridge volume/height)

1 evidences

Socket sealing with collagen matrix or membrane produced similar dimensional and histologic outcomes to other sealing approaches over 4–6 months.

Trust comment: Randomized pilot clinical trial with small groups (n total=22); limited power for small differences.

Study Details

PMID:37083911
Participants:22
Impact:No significant differences between socket sealing approaches
Trust score:3/5

Histologic hard and soft tissue formation

1 evidences

Socket sealing with collagen matrix or membrane produced similar dimensional and histologic outcomes to other sealing approaches over 4–6 months.

Trust comment: Randomized pilot clinical trial with small groups (n total=22); limited power for small differences.

Study Details

PMID:37083911
Participants:22
Impact:No detectable impact of sealing approach
Trust score:3/5

prevention of recession

1 evidences

Long-term follow-up in patients comparing collagen matrix to traditional graft; collagen matrix performed similarly for preventing recession and had better tissue match and patient preference.

Trust comment: Randomized split-mouth clinical trial with long 6–8 year follow-up but modest sample remaining (23), supporting moderate–high trust.

Study Details

PMID:33345312
Participants:23
Impact:no significant difference (ΔRec ≈ -0.07 mm CMX vs -0.17 mm FGG; P=0.71)
Trust score:4/5

tissue texture and color match

1 evidences

Long-term follow-up in patients comparing collagen matrix to traditional graft; collagen matrix performed similarly for preventing recession and had better tissue match and patient preference.

Trust comment: Randomized split-mouth clinical trial with long 6–8 year follow-up but modest sample remaining (23), supporting moderate–high trust.

Study Details

PMID:33345312
Participants:23
Impact:significantly better with collagen matrix
Trust score:4/5

patient preference/pain

1 evidences

Long-term follow-up in patients comparing collagen matrix to traditional graft; collagen matrix performed similarly for preventing recession and had better tissue match and patient preference.

Trust comment: Randomized split-mouth clinical trial with long 6–8 year follow-up but modest sample remaining (23), supporting moderate–high trust.

Study Details

PMID:33345312
Participants:23
Impact:patients preferred collagen matrix over free gingival graft
Trust score:4/5

maximum keratometry (K)

3 evidences

Clinical trial of corneal collagen cross-linking showing greater corneal flattening and vision improvement when the ectatic cone was centrally located.

Trust comment: Prospective randomized controlled clinical trial with 99 eyes/76 patients and quantitative outcomes; good quality for clinical intervention.

Study Details

PMID:22692521
Participants:76
Impact:decrease overall -1.60±3.40 D; central cones -2.60±4.50 D, paracentral -1.10±2.50 D, peripheral -0.40±1.20 D
Trust score:4/5

In patients with keratoconus, intracorneal ring segments plus corneal collagen crosslinking improved corneal topography and vision substantially; concurrent versus sequential timing showed equivalent outcomes.

Trust comment: Large randomized clinical trial (198 patients) with objective refractive and visual outcomes and 6-month follow-up.

Study Details

PMID:30928252
Participants:198
Impact:Mean decrease −2.5 D
Trust score:5/5

In 179 subjects with post-refractive corneal ectasia, corneal collagen crosslinking (CXL) reduced progression and improved vision at 1 year versus sham.

Trust comment: Prospective, randomized, multicenter controlled trial with substantial sample size and clear clinically meaningful endpoints.

Study Details

PMID:28655538
Participants:179
Impact:treatment ↓0.7 D from baseline; treatment vs control difference 1.3 D at 1 year (P<0.0001)
Trust score:5/5

disease activity (swollen joint count)

1 evidences

Replacing methotrexate with daily oral collagen type II (0.5 mg) worsened disease activity in patients with long-standing rheumatoid arthritis.

Trust comment: Randomized, double-blind comparative trial with clear clinical endpoints in 92 patients, providing moderate-high quality evidence for this intervention.

Study Details

PMID:9825751
Participants:92
Impact:increased significantly when methotrexate was substituted with 0.5 mg daily collagen type II (highly significant, P<0.0001)
Trust score:4/5

Achilles tendon cross-sectional area

1 evidences

Specific collagen peptide supplementation (5 g/day) combined with resistance training increased Achilles tendon size and muscle thickness more than placebo in young men.

Trust comment: Randomized, placebo-controlled trial with objective morphological outcomes but small sample size (n=40), giving moderately strong evidence.

Study Details

PMID:35403756
Participants:40
Impact:+11.0% (SCP) vs +4.7% (placebo), p=0.002
Trust score:4/5

muscle thickness (plantar flexors)

1 evidences

Specific collagen peptide supplementation (5 g/day) combined with resistance training increased Achilles tendon size and muscle thickness more than placebo in young men.

Trust comment: Randomized, placebo-controlled trial with objective morphological outcomes but small sample size (n=40), giving moderately strong evidence.

Study Details

PMID:35403756
Participants:40
Impact:+7.3% (SCP) vs +2.7% (placebo), p=0.014
Trust score:4/5

tendon stiffness

1 evidences

Specific collagen peptide supplementation (5 g/day) combined with resistance training increased Achilles tendon size and muscle thickness more than placebo in young men.

Trust comment: Randomized, placebo-controlled trial with objective morphological outcomes but small sample size (n=40), giving moderately strong evidence.

Study Details

PMID:35403756
Participants:40
Impact:increased in both groups with no significant difference between groups
Trust score:4/5

anterior keratocyte density

1 evidences

Traditional corneal cross-linking produced greater corneal structural changes (decreased keratocyte density, more edema/activation, deeper persistent stromal line) than transepithelial CXL.

Trust comment: Randomized eye-level study showing structural effects of corneal cross-linking (which targets corneal collagen); relevant to collagen structure but not to supplementation.

Study Details

PMID:23538618
Participants:35
Impact:significant decrease in traditional CXL group (P = 0.001); no significant change in transepithelial group
Trust score:3/5

stromal edema and keratocyte activation

1 evidences

Traditional corneal cross-linking produced greater corneal structural changes (decreased keratocyte density, more edema/activation, deeper persistent stromal line) than transepithelial CXL.

Trust comment: Randomized eye-level study showing structural effects of corneal cross-linking (which targets corneal collagen); relevant to collagen structure but not to supplementation.

Study Details

PMID:23538618
Participants:35
Impact:more evident after traditional CXL (P = 0.001)
Trust score:3/5

hyperreflective stromal line

1 evidences

Traditional corneal cross-linking produced greater corneal structural changes (decreased keratocyte density, more edema/activation, deeper persistent stromal line) than transepithelial CXL.

Trust comment: Randomized eye-level study showing structural effects of corneal cross-linking (which targets corneal collagen); relevant to collagen structure but not to supplementation.

Study Details

PMID:23538618
Participants:35
Impact:deeper and more persistent in traditional CXL group (P < 0.001)
Trust score:3/5

serum pro-c1α1 (type I collagen synthesis biomarker)

1 evidences

Eight weeks of daily Shilajit (500 or 1000 mg) increased serum pro-c1α1, a marker of type I collagen synthesis, compared with placebo.

Trust comment: Randomized controlled trial with biomarker outcomes in 35 men; small sample but randomized design and clear biomarker changes increase confidence.

Study Details

PMID:36546868
Participants:35
Impact:Low dose: 42.5 → 82.3 ng/mL; High dose: 42.7 → 113.1 ng/mL (significant; Low p=0.008, High p=0.007)
Trust score:4/5

proportion exceeding minimal clinically important difference

1 evidences

Eight weeks of daily Shilajit (500 or 1000 mg) increased serum pro-c1α1, a marker of type I collagen synthesis, compared with placebo.

Trust comment: Randomized controlled trial with biomarker outcomes in 35 men; small sample but randomized design and clear biomarker changes increase confidence.

Study Details

PMID:36546868
Participants:35
Impact:75% (high dose) vs 30% (placebo), p = 0.03
Trust score:4/5

visual acuity (logMAR)

1 evidences

Compared conventional (Dresden) vs accelerated corneal collagen cross-linking in progressive keratoconus; conventional protocol produced greater topographic flattening and some visual improvement at 6 months.

Trust comment: Small clinical comparative study with short (6-month) follow-up and limited sample size; outcomes measured objectively but power is limited.

Study Details

PMID:28230557
Participants:25
Impact:improved in conventional group (from 0.17 to 0.08; ≈ -0.09 logMAR)
Trust score:3/5

maximum keratometry

1 evidences

Compared conventional (Dresden) vs accelerated corneal collagen cross-linking in progressive keratoconus; conventional protocol produced greater topographic flattening and some visual improvement at 6 months.

Trust comment: Small clinical comparative study with short (6-month) follow-up and limited sample size; outcomes measured objectively but power is limited.

Study Details

PMID:28230557
Participants:25
Impact:decreased by 0.55 ± 0.89 D in conventional group
Trust score:3/5

mean keratometry

1 evidences

Compared conventional (Dresden) vs accelerated corneal collagen cross-linking in progressive keratoconus; conventional protocol produced greater topographic flattening and some visual improvement at 6 months.

Trust comment: Small clinical comparative study with short (6-month) follow-up and limited sample size; outcomes measured objectively but power is limited.

Study Details

PMID:28230557
Participants:25
Impact:decreased by 0.44 ± 0.63 D in conventional group
Trust score:3/5

uncorrected distance visual acuity (logMAR)

1 evidences

In keratoconus patients, corneal collagen cross-linking combined with intrastromal ring segments produced additional refractive and uncorrected visual acuity benefits at 1 year compared with cross-linking alone.

Trust comment: Prospective randomized pilot with objective ophthalmic measures and 1-year follow-up, but modest sample size limits generalizability.

Study Details

PMID:31707858
Participants:30
Impact:additional improvement of 0.16 logMAR in combined procedure (p=0.035)
Trust score:4/5

cylindrical power

1 evidences

In keratoconus patients, corneal collagen cross-linking combined with intrastromal ring segments produced additional refractive and uncorrected visual acuity benefits at 1 year compared with cross-linking alone.

Trust comment: Prospective randomized pilot with objective ophthalmic measures and 1-year follow-up, but modest sample size limits generalizability.

Study Details

PMID:31707858
Participants:30
Impact:improved by 1.16 D with combined procedure (p=0.014)
Trust score:4/5

spherical equivalent

1 evidences

In keratoconus patients, corneal collagen cross-linking combined with intrastromal ring segments produced additional refractive and uncorrected visual acuity benefits at 1 year compared with cross-linking alone.

Trust comment: Prospective randomized pilot with objective ophthalmic measures and 1-year follow-up, but modest sample size limits generalizability.

Study Details

PMID:31707858
Participants:30
Impact:improved by 1.40 D with combined procedure (p=0.038)
Trust score:4/5

new bone formation (8 weeks)

1 evidences

Randomized study of extraction socket treatments found that collagen plug alone (control) had more new bone and organic matrix at 8 weeks than grafted sites; adding growth factors led to faster graft particle turnover.

Trust comment: Randomized clinical histomorphometric study with moderate sample size and short (8-week) endpoint; findings relevant but limited by short follow-up.

Study Details

PMID:24683578
Participants:41
Impact:greater in collagen plug control sites compared with grafted sites
Trust score:3/5

residual graft particles

2 evidences

Randomized clinical trial comparing flapped vs flapless socket grafting with porcine bone and collagen membrane found similar histological outcomes after 3 months.

Trust comment: Randomized clinical trial with quantitative histomorphometry (34 patients); reasonable quality for histologic endpoints.

Study Details

PMID:24580835
Participants:34
Impact:~18.4% (no difference between groups)
Trust score:4/5

Randomized study of extraction socket treatments found that collagen plug alone (control) had more new bone and organic matrix at 8 weeks than grafted sites; adding growth factors led to faster graft particle turnover.

Trust comment: Randomized clinical histomorphometric study with moderate sample size and short (8-week) endpoint; findings relevant but limited by short follow-up.

Study Details

PMID:24683578
Participants:41
Impact:reduced when graft was combined with PRP or rhPDGF-BB (faster turnover)
Trust score:3/5

overall vital bone at 8 weeks

1 evidences

Randomized study of extraction socket treatments found that collagen plug alone (control) had more new bone and organic matrix at 8 weeks than grafted sites; adding growth factors led to faster graft particle turnover.

Trust comment: Randomized clinical histomorphometric study with moderate sample size and short (8-week) endpoint; findings relevant but limited by short follow-up.

Study Details

PMID:24683578
Participants:41
Impact:all modalities achieved significant new vital bone
Trust score:3/5

implant survival rate

2 evidences

Using a collagen membrane to cover sinus grafts improved implant survival, particularly for implants loaded at 6–9 months.

Trust comment: Direct clinical use of a collagen barrier with modest sample size and non-randomized clinical report design; moderate relevance but limited power.

Study Details

PMID:11669254
Participants:29
Impact:higher with collagen membrane (93.1% M+ vs 78.1% M-)
Trust score:3/5

Porcine collagen membrane performed as well as a PEG membrane for guided bone regeneration around single-tooth implants at 5 years.

Trust comment: Randomized controlled clinical trial with 5-year follow-up and objective CBCT outcomes; moderate sample size.

Study Details

PMID:24299007
Participants:32
Impact:100% (both groups at 5 years)
Trust score:4/5

buccal vertical bone gain

1 evidences

Porcine collagen membrane performed as well as a PEG membrane for guided bone regeneration around single-tooth implants at 5 years.

Trust comment: Randomized controlled clinical trial with 5-year follow-up and objective CBCT outcomes; moderate sample size.

Study Details

PMID:24299007
Participants:32
Impact:+4.3 mm (collagen group mean gain over 5 years)
Trust score:4/5

mucosal thickness

1 evidences

Porcine collagen membrane performed as well as a PEG membrane for guided bone regeneration around single-tooth implants at 5 years.

Trust comment: Randomized controlled clinical trial with 5-year follow-up and objective CBCT outcomes; moderate sample size.

Study Details

PMID:24299007
Participants:32
Impact:1.4 mm (collagen group mean)
Trust score:4/5

epithelial thickness

1 evidences

Corneal collagen cross-linking led to significant epithelial thinning and a more regular epithelial thickness profile, with no consistent stromal changes at 1–3 months.

Trust comment: Prospective clinical imaging study with objective OCT measurements but limited sample and short-term follow-up.

Study Details

PMID:24763478
Participants:30
Impact:decreased in multiple regions to ~49.3 μm (significant)
Trust score:3/5

epithelial thickness variability

1 evidences

Corneal collagen cross-linking led to significant epithelial thinning and a more regular epithelial thickness profile, with no consistent stromal changes at 1–3 months.

Trust comment: Prospective clinical imaging study with objective OCT measurements but limited sample and short-term follow-up.

Study Details

PMID:24763478
Participants:30
Impact:SD decreased by 3–6 μm (more regularized) at 3 months
Trust score:3/5

stromal thickness

1 evidences

Corneal collagen cross-linking led to significant epithelial thinning and a more regular epithelial thickness profile, with no consistent stromal changes at 1–3 months.

Trust comment: Prospective clinical imaging study with objective OCT measurements but limited sample and short-term follow-up.

Study Details

PMID:24763478
Participants:30
Impact:no significant or consistent change
Trust score:3/5

fat-free mass

1 evidences

Daily 15 g specific collagen peptides plus 12-week resistance training increased fat-free mass and reduced fat mass more than placebo in overweight middle-aged men.

Trust comment: Double-blind, randomized, placebo-controlled trial with objective DXA and strength measures; per-protocol sample moderate.

Study Details

PMID:33946565
Participants:61
Impact:+3.42 kg (CP group mean); vs +1.83 kg (placebo); collagen provided ~+1.59 kg additional gain (P = 0.010)
Trust score:4/5

muscle strength (isometric leg press)

1 evidences

Daily 15 g specific collagen peptides plus 12-week resistance training increased fat-free mass and reduced fat mass more than placebo in overweight middle-aged men.

Trust comment: Double-blind, randomized, placebo-controlled trial with objective DXA and strength measures; per-protocol sample moderate.

Study Details

PMID:33946565
Participants:61
Impact:+163 N (~16.3 kg) (CP) vs +100 N (~10 kg) (placebo); between-group difference not statistically significant
Trust score:4/5

myofibrillar protein synthesis (exercised post-prandial)

1 evidences

A post-exercise beverage containing 25 g whey plus 5 g collagen increased plasma amino acids and raised myofibrillar and muscle connective protein synthesis at rest; after exercise it increased myofibrillar but not connective synthesis.

Trust comment: Carefully controlled randomized trial with stable-isotope tracer muscle biopsies; small but mechanistically robust.

Study Details

PMID:39501478
Participants:28
Impact:0.052%·h−1 (BLEND) vs 0.039%·h−1 (PLA); increased
Trust score:4/5

muscle connective protein synthesis (rested post-prandial)

1 evidences

A post-exercise beverage containing 25 g whey plus 5 g collagen increased plasma amino acids and raised myofibrillar and muscle connective protein synthesis at rest; after exercise it increased myofibrillar but not connective synthesis.

Trust comment: Carefully controlled randomized trial with stable-isotope tracer muscle biopsies; small but mechanistically robust.

Study Details

PMID:39501478
Participants:28
Impact:0.062%·h−1 (BLEND) vs 0.051%·h−1 (PLA); increased
Trust score:4/5

plasma glycine availability (post-prandial)

1 evidences

A post-exercise beverage containing 25 g whey plus 5 g collagen increased plasma amino acids and raised myofibrillar and muscle connective protein synthesis at rest; after exercise it increased myofibrillar but not connective synthesis.

Trust comment: Carefully controlled randomized trial with stable-isotope tracer muscle biopsies; small but mechanistically robust.

Study Details

PMID:39501478
Participants:28
Impact:increased (significant rise vs placebo at 30–90 min)
Trust score:4/5

Pain (Visual Analogue Scale, VAS)

1 evidences

Rehab plus oral collagen-containing supplement produced greater and more sustained improvements in pain, disability, and physical QoL than rehab alone.

Trust comment: Randomized human trial but small, unblinded, and supplement contained multiple active ingredients so effects cannot be attributed to collagen alone.

Study Details

PMID:33568038
Participants:60
Impact:greater decrease vs rehabilitation alone (improvement sustained at follow-up)
Trust score:3/5

Disability (Oswestry Disability Index, ODI)

1 evidences

Rehab plus oral collagen-containing supplement produced greater and more sustained improvements in pain, disability, and physical QoL than rehab alone.

Trust comment: Randomized human trial but small, unblinded, and supplement contained multiple active ingredients so effects cannot be attributed to collagen alone.

Study Details

PMID:33568038
Participants:60
Impact:greater improvement vs rehabilitation alone (sustained)
Trust score:3/5

Physical component of quality of life (SF-12 physical)

1 evidences

Rehab plus oral collagen-containing supplement produced greater and more sustained improvements in pain, disability, and physical QoL than rehab alone.

Trust comment: Randomized human trial but small, unblinded, and supplement contained multiple active ingredients so effects cannot be attributed to collagen alone.

Study Details

PMID:33568038
Participants:60
Impact:greater improvement vs rehabilitation alone (sustained)
Trust score:3/5

Pain scores

1 evidences

Collagen cross-linking reduced corneal thickness short-term but provided no sustained improvement in pain, clarity, or vision and had higher rates of recurrent epithelial defects.

Trust comment: Randomized controlled human study with 12-month follow-up; moderate sample size but clear outcome measures and reported harms.

Study Details

PMID:33017120
Participants:42
Impact:no consistent improvement vs control
Trust score:4/5

Recurrent epithelial defect (adverse event)

1 evidences

Collagen cross-linking reduced corneal thickness short-term but provided no sustained improvement in pain, clarity, or vision and had higher rates of recurrent epithelial defects.

Trust comment: Randomized controlled human study with 12-month follow-up; moderate sample size but clear outcome measures and reported harms.

Study Details

PMID:33017120
Participants:42
Impact:12% incidence in CXL group (some required intervention)
Trust score:4/5

Refractive regression (spherical equivalent)

1 evidences

Adding intrastromal collagen cross-linking to hyperopic LASIK reduced long-term regression and gave better uncorrected vision than LASIK alone at 2 years.

Trust comment: Contralateral randomized human study with 2-year follow-up and objective refractive outcomes, though sample is modest.

Study Details

PMID:23447898
Participants:34
Impact:mean regression +0.22 D with CXL vs +0.72 D without CXL at 2 years (less regression with CXL)
Trust score:4/5

Residual cylinder

1 evidences

Adding intrastromal collagen cross-linking to hyperopic LASIK reduced long-term regression and gave better uncorrected vision than LASIK alone at 2 years.

Trust comment: Contralateral randomized human study with 2-year follow-up and objective refractive outcomes, though sample is modest.

Study Details

PMID:23447898
Participants:34
Impact:mean 0.65 D (CXL) vs 0.76 D (no CXL) at 2 years
Trust score:4/5

surgical site infection (SSI) incidence

1 evidences

Adding gentamicin-collagen sponges did not reduce surgical site infections after hemiarthroplasty in elderly patients.

Trust comment: Large multicenter randomized trial with modified ITT analysis and objective clinical endpoints.

Study Details

PMID:25737375
Participants:684
Impact:-0.5 percentage points (4.9% vs 5.4%, no significant difference)
Trust score:5/5

deep SSI incidence

1 evidences

Adding gentamicin-collagen sponges did not reduce surgical site infections after hemiarthroplasty in elderly patients.

Trust comment: Large multicenter randomized trial with modified ITT analysis and objective clinical endpoints.

Study Details

PMID:25737375
Participants:684
Impact:no significant difference (4.3% vs 4.5%, NS)
Trust score:5/5

superficial SSI incidence

1 evidences

Adding gentamicin-collagen sponges did not reduce surgical site infections after hemiarthroplasty in elderly patients.

Trust comment: Large multicenter randomized trial with modified ITT analysis and objective clinical endpoints.

Study Details

PMID:25737375
Participants:684
Impact:no significant difference (0.6% vs 0.8%, NS)
Trust score:5/5

operative time and pain

1 evidences

Porcine-derived collagen matrix (PDCM) produced better root coverage and less pain/time than connective tissue grafts in smokers.

Trust comment: Randomized controlled clinical trial with clear clinical measures but small sample size (28 patients).

Study Details

PMID:36057652
Participants:28
Impact:reduced in PDCM group (significant)
Trust score:4/5

symptomatic relief (discomfort)

1 evidences

Collagen cross-linking provided short-term symptomatic relief, reduced central corneal thickness and caused anterior stromal compaction in PBK patients.

Trust comment: Prospective interventional study with objective measures but small sample and limited duration of effect.

Study Details

PMID:23953101
Participants:24
Impact:improved at 1 month, effect diminished by 3 months
Trust score:3/5

complete hemostasis within 10 min

1 evidences

A collagen-based composite (CoStasis) achieved faster and more complete hemostasis than manual compression with a collagen sponge.

Trust comment: Prospective controlled clinical trial with clear, objective endpoints and large effect sizes, though moderate sample size.

Study Details

PMID:11083396
Participants:47
Impact:100% (CoStasis) vs 48% (control)
Trust score:4/5

complete hemostasis within 2 min

1 evidences

A collagen-based composite (CoStasis) achieved faster and more complete hemostasis than manual compression with a collagen sponge.

Trust comment: Prospective controlled clinical trial with clear, objective endpoints and large effect sizes, though moderate sample size.

Study Details

PMID:11083396
Participants:47
Impact:>60% (CoStasis) vs 5% (control)
Trust score:4/5

time to controlled bleeding / time to complete hemostasis

1 evidences

A collagen-based composite (CoStasis) achieved faster and more complete hemostasis than manual compression with a collagen sponge.

Trust comment: Prospective controlled clinical trial with clear, objective endpoints and large effect sizes, though moderate sample size.

Study Details

PMID:11083396
Participants:47
Impact:significantly faster with CoStasis (P<0.0001)
Trust score:4/5

Treatment duration

1 evidences

Adding UV-A/riboflavin corneal collagen cross-linking sped healing and shortened treatment time for moderate bacterial corneal ulcers.

Trust comment: Randomized controlled trial with clear, significant outcomes but modest sample size (n=32).

Study Details

PMID:25710507
Participants:32
Impact:shorter in CXL group (mean 17.2 ± 4.1 days) vs control (24.7 ± 5.5 days)
Trust score:4/5

Epithelial defect size

1 evidences

Adding UV-A/riboflavin corneal collagen cross-linking sped healing and shortened treatment time for moderate bacterial corneal ulcers.

Trust comment: Randomized controlled trial with clear, significant outcomes but modest sample size (n=32).

Study Details

PMID:25710507
Participants:32
Impact:smaller at days 7 and 14 in CXL group (P = 0.001)
Trust score:4/5

Area of infiltrates

1 evidences

Adding UV-A/riboflavin corneal collagen cross-linking sped healing and shortened treatment time for moderate bacterial corneal ulcers.

Trust comment: Randomized controlled trial with clear, significant outcomes but modest sample size (n=32).

Study Details

PMID:25710507
Participants:32
Impact:smaller at days 7 (P = 0.001) and 14 (P < 0.001) in CXL group
Trust score:4/5

Corneal surface temperature (pre-treatment riboflavin, epi-off)

1 evidences

Corneal collagen crosslinking and riboflavin application altered corneal surface temperature; pre-heated oxygen raised temperature more markedly.

Trust comment: Well-controlled intra-individual randomized design but small sample sizes (14 keratoconus, 12 healthy), limiting precision.

Study Details

PMID:37983864
Participants:26
Impact:decrease of −1.1 ± 1.0°C (p < 0.001)
Trust score:4/5

Corneal surface temperature (during CXL, first half)

1 evidences

Corneal collagen crosslinking and riboflavin application altered corneal surface temperature; pre-heated oxygen raised temperature more markedly.

Trust comment: Well-controlled intra-individual randomized design but small sample sizes (14 keratoconus, 12 healthy), limiting precision.

Study Details

PMID:37983864
Participants:26
Impact:increase of +0.7 ± ~1.0°C (significant for both epi-on and epi-off)
Trust score:4/5

Effect of pre-heated oxygen

1 evidences

Corneal collagen crosslinking and riboflavin application altered corneal surface temperature; pre-heated oxygen raised temperature more markedly.

Trust comment: Well-controlled intra-individual randomized design but small sample sizes (14 keratoconus, 12 healthy), limiting precision.

Study Details

PMID:37983864
Participants:26
Impact:surface temperature increase of +1.8 ± 0.2°C (p < 0.001)
Trust score:4/5

Back pain (face scale)

1 evidences

In elderly osteoporotic women, alendronate increased lumbar BMD and reduced bone resorption more than etidronate; both treatments reduced back pain.

Trust comment: Open-label head-to-head prospective study with small sample but clear biochemical and BMD differences.

Study Details

PMID:16385649
Participants:50
Impact:decreased in both groups
Trust score:3/5

scar severity score

1 evidences

Randomized trial comparing phenol deep peel vs percutaneous collagen induction + TCA for atrophic post-acne scars; both treatments produced large scar improvements.

Trust comment: Small randomized trial with subjective outcome measures and limited sample size, moderate risk of bias.

Study Details

PMID:22397516
Participants:24
Impact:-75.12% (phenol) and -69.43% (PCI + TCA)
Trust score:3/5

hemostasis time

1 evidences

Randomized trial comparing a collagen-based vascular hemostasis device (VasoSeal) to manual compression after PTCA; VasoSeal reduced hemostasis time, ambulation time, and hospital/nursing resource use.

Trust comment: Randomized study with clinically relevant outcomes but abstract lacks detailed effect sizes and is older, limiting precision.

Study Details

PMID:7497486
Participants:101
Impact:significantly reduced with collagen VHD versus manual compression (exact values not reported in abstract)
Trust score:3/5

time to ambulation and hospital stay

1 evidences

Randomized trial comparing a collagen-based vascular hemostasis device (VasoSeal) to manual compression after PTCA; VasoSeal reduced hemostasis time, ambulation time, and hospital/nursing resource use.

Trust comment: Randomized study with clinically relevant outcomes but abstract lacks detailed effect sizes and is older, limiting precision.

Study Details

PMID:7497486
Participants:101
Impact:significantly reduced with VHD (exact values not reported in abstract)
Trust score:3/5

minor groin complications

1 evidences

Randomized trial comparing a collagen-based vascular hemostasis device (VasoSeal) to manual compression after PTCA; VasoSeal reduced hemostasis time, ambulation time, and hospital/nursing resource use.

Trust comment: Randomized study with clinically relevant outcomes but abstract lacks detailed effect sizes and is older, limiting precision.

Study Details

PMID:7497486
Participants:101
Impact:trend toward increase with VHD (no major complications in either arm)
Trust score:3/5

COL3A1-4 allele — ACS risk

1 evidences

Genetic association studies showing COL3A1 polymorphisms influence coronary disease risk; certain alleles were protective while others modified treatment response.

Trust comment: Large multicohort genetic association analysis with consistent effect estimates; good sample size and external validation.

Study Details

PMID:12149201
Participants:2157
Impact:associated with reduced acute coronary syndrome risk (OR = 0.57) and reduced stable angina risk (OR = 0.35)
Trust score:4/5

COL3A1-4 allele — OPUS composite outcome

1 evidences

Genetic association studies showing COL3A1 polymorphisms influence coronary disease risk; certain alleles were protective while others modified treatment response.

Trust comment: Large multicohort genetic association analysis with consistent effect estimates; good sample size and external validation.

Study Details

PMID:12149201
Participants:2157
Impact:associated with reduced composite risk in OPUS cohort (RR = 0.41)
Trust score:4/5

COL3A1-3 allele — treatment interaction

1 evidences

Genetic association studies showing COL3A1 polymorphisms influence coronary disease risk; certain alleles were protective while others modified treatment response.

Trust comment: Large multicohort genetic association analysis with consistent effect estimates; good sample size and external validation.

Study Details

PMID:12149201
Participants:2157
Impact:associated with increased composite risk in orbofiban-treated patients (RR = 1.65) but protective in placebo (RR = 0.53)
Trust score:4/5

integrated myofibrillar protein synthesis (MPS)

1 evidences

In older men, twice-daily whey or pea protein (2×25 g) increased integrated muscle protein synthesis by ~9%, whereas twice-daily collagen (2×25 g) did not change integrated MPS.

Trust comment: Well-conducted double-blind randomized trial with direct measurements of integrated MPS and appropriate controls, though limited to older males and modest sample size.

Study Details

PMID:38762187
Participants:31
Impact:≈+9% in whey and pea (supplemental vs control); no significant change in collagen (P=0.237)
Trust score:5/5

postprandial plasma leucine / EAAs

1 evidences

In older men, twice-daily whey or pea protein (2×25 g) increased integrated muscle protein synthesis by ~9%, whereas twice-daily collagen (2×25 g) did not change integrated MPS.

Trust comment: Well-conducted double-blind randomized trial with direct measurements of integrated MPS and appropriate controls, though limited to older males and modest sample size.

Study Details

PMID:38762187
Participants:31
Impact:greater leucine/EAAs after whey (significantly higher than collagen at multiple timepoints)
Trust score:5/5

mTORC1 / rpS6 / AKT anabolic signaling (acute)

1 evidences

In older men, twice-daily whey or pea protein (2×25 g) increased integrated muscle protein synthesis by ~9%, whereas twice-daily collagen (2×25 g) did not change integrated MPS.

Trust comment: Well-conducted double-blind randomized trial with direct measurements of integrated MPS and appropriate controls, though limited to older males and modest sample size.

Study Details

PMID:38762187
Participants:31
Impact:increased with supplemental protein feeding (supplemental > basal; P<0.001 for several markers)
Trust score:5/5

oral mucositis severity (WHO / OMAS)

1 evidences

Use of a hyaluronic acid spray containing amino acids that are collagen precursors (Mucosamin®), especially with professional oral hygiene, reduced severity and duration of oral mucositis after stem cell transplant.

Trust comment: Moderately sized case-control clinical study showing consistent benefits, but non-randomized group allocation and potential confounding limit certainty.

Study Details

PMID:29921408
Participants:137
Impact:reduced in Mucosamin groups vs controls (WHO and OMAS; p≤0.001 for OMAS; WHO differences significant between groups)
Trust score:3/5

duration of mucositis

1 evidences

Use of a hyaluronic acid spray containing amino acids that are collagen precursors (Mucosamin®), especially with professional oral hygiene, reduced severity and duration of oral mucositis after stem cell transplant.

Trust comment: Moderately sized case-control clinical study showing consistent benefits, but non-randomized group allocation and potential confounding limit certainty.

Study Details

PMID:29921408
Participants:137
Impact:shorter with Mucosamin + professional hygiene vs standard care (Group A vs B p=0.02; vs D p=0.03)
Trust score:3/5

patient-reported pain (VAS)

1 evidences

Use of a hyaluronic acid spray containing amino acids that are collagen precursors (Mucosamin®), especially with professional oral hygiene, reduced severity and duration of oral mucositis after stem cell transplant.

Trust comment: Moderately sized case-control clinical study showing consistent benefits, but non-randomized group allocation and potential confounding limit certainty.

Study Details

PMID:29921408
Participants:137
Impact:lower discomfort reported with Mucosamin combined with hygiene (statistically significant differences reported)
Trust score:3/5

postoperative wound infection rate

2 evidences

In elective colorectal surgery, adding a gentamicin-collagen sponge to systemic antibiotics lowered postoperative wound infection rates compared with systemic antibiotics alone.

Trust comment: Randomized clinical trial with clear clinically meaningful reduction in wound infections; robust sample though older single-study result.

Study Details

PMID:9167147
Participants:221
Impact:5.6% with gentamicin-collagen sponge vs 18.4% control; absolute −12.8 percentage points (p<0.01)
Trust score:4/5

Large randomized trial showing gentamicin-laced collagen tampons placed over prosthetic mesh reduced postoperative wound infections after groin hernia repair.

Trust comment: Large randomized controlled trial showing a clinically meaningful reduction in infections; direct use of collagen as a medical product supports relevance and trustworthiness.

Study Details

PMID:11266253
Participants:595
Impact:0.3% (gentamicin-collagen) vs 2.0% (control); p=0.04
Trust score:4/5

tolerability / adverse events

1 evidences

In elective colorectal surgery, adding a gentamicin-collagen sponge to systemic antibiotics lowered postoperative wound infection rates compared with systemic antibiotics alone.

Trust comment: Randomized clinical trial with clear clinically meaningful reduction in wound infections; robust sample though older single-study result.

Study Details

PMID:9167147
Participants:221
Impact:no adverse events attributable to the gentamicin-collagen sponge reported
Trust score:4/5

alveolar bone width loss

1 evidences

Using an absorbable gentamicin‑impregnated collagen matrix to seal extraction sockets produced very small bone width loss and more blood vessel ingrowth but no statistically significant reduction in resorption overall.

Trust comment: Clinical comparative study with a moderate sample size and objective measurements, but differences were overall non‑significant (borderline in one comparison).

Study Details

PMID:20614049
Participants:125
Impact:0.1 mm loss in collagen+gentamicin group (group C) vs 0.3 mm (group A) and 0.8 mm (group B)
Trust score:3/5

vascular ingrowth

1 evidences

Using an absorbable gentamicin‑impregnated collagen matrix to seal extraction sockets produced very small bone width loss and more blood vessel ingrowth but no statistically significant reduction in resorption overall.

Trust comment: Clinical comparative study with a moderate sample size and objective measurements, but differences were overall non‑significant (borderline in one comparison).

Study Details

PMID:20614049
Participants:125
Impact:increased (qualitative)
Trust score:3/5

keratoconus progression

1 evidences

Epithelium‑off corneal collagen cross‑linking halted keratoconus progression and reduced maximum K, while transepithelial treatment was less effective and many patients progressed.

Trust comment: Prospective randomized controlled trial with 3‑year follow‑up showing clear, statistically significant differences in primary outcomes.

Study Details

PMID:26266436
Participants:70
Impact:epithelium‑off: 0% progressed; transepithelial: 55% progressed (20/36)
Trust score:5/5

left atrial epicardial conduction time (LAECT)

1 evidences

Longer left atrial epicardial conduction time (LAECT) was associated with more AF recurrences; higher interstitial collagen fibre density correlated with shorter LAECT.

Trust comment: Well‑characterized single‑center substudy with invasive electrophysiological and histological measures and 2‑year follow‑up; observational limitations apply.

Study Details

PMID:35264365
Participants:121
Impact:182±43 ms with recurrence vs 147±29 ms without recurrence (≈+35 ms)
Trust score:4/5

AF recurrence risk (per 10 ms LAECT)

1 evidences

Longer left atrial epicardial conduction time (LAECT) was associated with more AF recurrences; higher interstitial collagen fibre density correlated with shorter LAECT.

Trust comment: Well‑characterized single‑center substudy with invasive electrophysiological and histological measures and 2‑year follow‑up; observational limitations apply.

Study Details

PMID:35264365
Participants:121
Impact:HR ≈1.08–1.11 per 10 ms increase
Trust score:4/5

interstitial collagen fibre density

1 evidences

Longer left atrial epicardial conduction time (LAECT) was associated with more AF recurrences; higher interstitial collagen fibre density correlated with shorter LAECT.

Trust comment: Well‑characterized single‑center substudy with invasive electrophysiological and histological measures and 2‑year follow‑up; observational limitations apply.

Study Details

PMID:35264365
Participants:121
Impact:higher density associated with shorter LAECT (~−5 ms per +1 fibre/mm²)
Trust score:4/5

collagen cross‑link ratio

1 evidences

Teriparatide treatment produced bone with lower matrix mineralization, lower mineral crystallinity and reduced collagen cross‑link ratio compared with placebo, resembling younger bone matrix characteristics.

Trust comment: Randomized, double‑blind, placebo‑controlled trial but small biopsy subgroup; molecular measures are robust though sample size is limited.

Study Details

PMID:15914535
Participants:38
Impact:decreased in 20 µg and 40 µg teriparatide groups vs placebo
Trust score:4/5

matrix mineralization (mineral:matrix)

1 evidences

Teriparatide treatment produced bone with lower matrix mineralization, lower mineral crystallinity and reduced collagen cross‑link ratio compared with placebo, resembling younger bone matrix characteristics.

Trust comment: Randomized, double‑blind, placebo‑controlled trial but small biopsy subgroup; molecular measures are robust though sample size is limited.

Study Details

PMID:15914535
Participants:38
Impact:decreased with teriparatide
Trust score:4/5

mineral crystallinity

1 evidences

Teriparatide treatment produced bone with lower matrix mineralization, lower mineral crystallinity and reduced collagen cross‑link ratio compared with placebo, resembling younger bone matrix characteristics.

Trust comment: Randomized, double‑blind, placebo‑controlled trial but small biopsy subgroup; molecular measures are robust though sample size is limited.

Study Details

PMID:15914535
Participants:38
Impact:decreased with teriparatide
Trust score:4/5

vertical bone gain (VBG)

3 evidences

Adding anorganic bovine bone to a collagen membrane (CPRT) produced greater attachment gains and more vertical bone gain than collagen membrane alone after 1 year.

Trust comment: Randomized controlled study with clear clinical and surgical endpoints gives moderate-high trust.

Study Details

PMID:11895280
Participants:34
Impact:test (CPRT): 5.23 ±1.30 mm vs control: 3.82 ±1.28 mm (P<0.01)
Trust score:4/5

Randomized clinical trial in 40 patients comparing d-PTFE (non-resorbable) membranes versus Ti-mesh covered with cross-linked collagen membrane for guided bone regeneration; both achieved similar vertical bone gain and comparable healing complication rates.

Trust comment: Randomized, double-blind clinical trial with 40 patients and predefined outcomes; single-center pilot design limits generalizability but methodology is solid.

Study Details

PMID:28745035
Participants:40
Impact:≈4.2 mm (d-PTFE) vs ≈4.1 mm (Ti mesh + collagen); no significant difference
Trust score:4/5

In this randomized trial, covering customized titanium mesh with a resorbable (cross-linked collagen) membrane tended to reduce healing complications and improve regenerated bone volume compared with mesh alone, though differences were not statistically significant.

Trust comment: - Checklist: - Confirm whether study tests Collagen effect on humans and list top outcomes. - Determine participant count (completed subjects). - Rate study quality (1–5) with brief justification. - Report quantitative change per outcome and give a very short plain-language summary. Justification: This is a randomized, investigator-blinded clinical trial directly testing the effect of adding a resorbable collagen membrane (vs no membrane) with objective measures; good design but small sample (n=30) and many outcomes were not statistically significant, so moderate-high trust (4).

Study Details

PMID:34551168
Participants:30
Impact:observed increase from 4.74 mm to 6.36 mm (+1.62 mm, NS)
Trust score:4/5

overall healing complication rate

1 evidences

Randomized clinical trial in 40 patients comparing d-PTFE (non-resorbable) membranes versus Ti-mesh covered with cross-linked collagen membrane for guided bone regeneration; both achieved similar vertical bone gain and comparable healing complication rates.

Trust comment: Randomized, double-blind clinical trial with 40 patients and predefined outcomes; single-center pilot design limits generalizability but methodology is solid.

Study Details

PMID:28745035
Participants:40
Impact:15.0% (d-PTFE) vs 21.1% (Ti mesh + collagen); no significant difference
Trust score:4/5

surgical complication rate (neurological)

1 evidences

Randomized clinical trial in 40 patients comparing d-PTFE (non-resorbable) membranes versus Ti-mesh covered with cross-linked collagen membrane for guided bone regeneration; both achieved similar vertical bone gain and comparable healing complication rates.

Trust comment: Randomized, double-blind clinical trial with 40 patients and predefined outcomes; single-center pilot design limits generalizability but methodology is solid.

Study Details

PMID:28745035
Participants:40
Impact:5% (d-PTFE) vs 15.8% (Ti mesh + collagen); difference not statistically significant
Trust score:4/5

peri-implant marginal bone level at follow-up

1 evidences

Pilot RCT (27 patients) comparing PRF membranes versus standard DBBM plus resorbable collagen membrane for augmented sites; implant survival similar and PRF group had a slightly better peri-implant marginal bone level at 2-year follow-up.

Trust comment: Randomized pilot RCT with small sample and appropriate clinical/radiographic follow-up; limited power but direct clinical relevance to use of collagen membranes.

Study Details

PMID:33554323
Participants:27
Impact:PRF 0.26 mm vs control 0.68 mm (mean difference −0.43 mm; p=0.03)
Trust score:3/5

clinical performance of restorations (USPHS criteria)

1 evidences

Split-mouth RCT (30 patients enrolled; 24 completed at 5 years) comparing conventional total-etch adhesive versus dentine deproteinization with 10% NaOCl (collagen removal); no difference in clinical performance after 5 years.

Trust comment: Long-term (5-year) randomized split-mouth clinical trial with reasonable follow-up; direct manipulation of dentin collagen and clinically relevant endpoints.

Study Details

PMID:24739486
Participants:24
Impact:no significant difference after 5 years between deproteinization (10% NaOCl) and conventional technique
Trust score:4/5

complete hemostasis within 10 minutes

1 evidences

A sprayable collagen-thrombin-plasma composite stopped diffuse liver bleeding faster and more reliably than a collagen sponge applied with pressure.

Trust comment: Multicenter randomized controlled trial with clear, clinically relevant endpoints and complete reporting of outcomes.

Study Details

PMID:11030881
Participants:67
Impact:100% (38/38) experimental vs 69% (20/29) control
Trust score:5/5

oil secretion

1 evidences

In vivo dermatological evaluation of topical formulations containing lyophilized hydrolyzed blue shark cartilage (collagen) applied to inner wrists of volunteers with skin measurements at baseline, 10 min and 20 min.

Trust comment: Human volunteer dermatological test with 66 participants and objective instrument measures but short-term (minutes) assessment limits clinical relevance for sustained effects.

Study Details

PMID:36286457
Participants:66
Impact:sample F11 significantly reduced oil secretion (reduced vs baseline at 10–20 min)
Trust score:3/5

wrinkle/3D appearance (texture)

1 evidences

In vivo dermatological evaluation of topical formulations containing lyophilized hydrolyzed blue shark cartilage (collagen) applied to inner wrists of volunteers with skin measurements at baseline, 10 min and 20 min.

Trust comment: Human volunteer dermatological test with 66 participants and objective instrument measures but short-term (minutes) assessment limits clinical relevance for sustained effects.

Study Details

PMID:36286457
Participants:66
Impact:formulation F11 improved texture and smoothed 3D wrinkle appearance (10–20 min)
Trust score:3/5

between-group effect on tendinous remodeling

1 evidences

Double-blind placebo-controlled randomized trial in recreationally active young men testing 15 g/day collagen peptides vs placebo during 15 weeks of lower-body resistance training; measured tendon size and mechanical properties.

Trust comment: Well-designed double-blind RCT with objective MRI and mechanical measures but modest sample size; conclusions robust that CP did not outperform placebo.

Study Details

PMID:37436929
Participants:39
Impact:no difference between collagen peptide and placebo groups (no augmentation of RT-induced adaptations)
Trust score:4/5

vastus lateralis aponeurosis area

1 evidences

Double-blind placebo-controlled randomized trial in recreationally active young men testing 15 g/day collagen peptides vs placebo during 15 weeks of lower-body resistance training; measured tendon size and mechanical properties.

Trust comment: Well-designed double-blind RCT with objective MRI and mechanical measures but modest sample size; conclusions robust that CP did not outperform placebo.

Study Details

PMID:37436929
Participants:39
Impact:within-group increases ~CP +10.0%; PLA +9.4% (both significant)
Trust score:4/5

patellar tendon mechanical properties

1 evidences

Double-blind placebo-controlled randomized trial in recreationally active young men testing 15 g/day collagen peptides vs placebo during 15 weeks of lower-body resistance training; measured tendon size and mechanical properties.

Trust comment: Well-designed double-blind RCT with objective MRI and mechanical measures but modest sample size; conclusions robust that CP did not outperform placebo.

Study Details

PMID:37436929
Participants:39
Impact:within-group increases in stiffness (CP +17.3%; PLA +20.9%) and Young's modulus (CP +17.8%; PLA +20.6%); decreases in elongation and strain in both groups
Trust score:4/5

alveolar ridge resorption (vertical and horizontal)

1 evidences

Randomized trial comparing ridge preservation techniques including demineralized bovine bone mineral with 10% collagen plus collagen matrix or soft-tissue graft versus controls; CBCT assessed ridge changes after 6 months.

Trust comment: Randomized controlled clinical trial with CBCT objective outcomes and clear comparative results—moderate to high trustworthiness.

Study Details

PMID:23163915
Participants:40
Impact:DBBM-C with collagen matrix or autogenous soft-tissue graft resulted in less vertical and horizontal ridge changes vs controls (reduced resorption)
Trust score:4/5

localized ridge width changes

1 evidences

Randomized trial comparing ridge preservation techniques including demineralized bovine bone mineral with 10% collagen plus collagen matrix or soft-tissue graft versus controls; CBCT assessed ridge changes after 6 months.

Trust comment: Randomized controlled clinical trial with CBCT objective outcomes and clear comparative results—moderate to high trustworthiness.

Study Details

PMID:23163915
Participants:40
Impact:examples at 1 mm below crest: control −3.3 mm, β‑TCP −6.1 mm, DBBM‑C/CM −1.2 mm, DBBM‑C/PG −1.4 mm
Trust score:4/5

surgical success rate

3 evidences

Randomized trial comparing atelocollagen implant vs mitomycin C during trabeculectomy; the collagen implant group had less pressure reduction and lower surgical success than MMC.

Trust comment: Prospective randomized trial in humans but small sample and single-center limits generalizability.

Study Details

PMID:24401481
Participants:30
Impact:40% (OLO) vs 93.3% (MMC) at 12 months, p=0.01
Trust score:3/5

In phacotrabeculectomy, the collagen matrix implant and mitomycin C produced similar intraocular pressure lowering and success rates at 12 months.

Trust comment: Prospective randomized trial directly testing a collagen matrix implant with clear clinical endpoints; single-centre and nonblinded but well-reported.

Study Details

PMID:30924600
Participants:53
Impact:92.6% (OLO) vs 92.3% (MMC); no significant difference
Trust score:4/5

Postoperative oral prednisolone lowered serum markers of collagen synthesis systemically but did not improve surgical success of Molteno implantation over 6 months.

Trust comment: Randomized clinical trial in humans but small sample and clinical endpoint differences were not statistically significant.

Study Details

PMID:10071149
Participants:22
Impact:no significant improvement (82% control vs 50% prednisolone; p=0.18)
Trust score:3/5

meniscal tissue growth

1 evidences

A multicentre randomized trial found collagen meniscus implants supported new meniscus-like tissue growth and improved activity and reoperation rates in patients with chronic meniscal injury.

Trust comment: Large, multicentre randomized prospective trial with long follow-up and objective surgical/clinical endpoints.

Study Details

PMID:18594088
Participants:311
Impact:significantly increased at 1 year (p = 0.001)
Trust score:5/5

activity level (chronic group)

1 evidences

A multicentre randomized trial found collagen meniscus implants supported new meniscus-like tissue growth and improved activity and reoperation rates in patients with chronic meniscal injury.

Trust comment: Large, multicentre randomized prospective trial with long follow-up and objective surgical/clinical endpoints.

Study Details

PMID:18594088
Participants:311
Impact:significantly improved vs control (p = 0.02)
Trust score:5/5

reoperation rate (chronic group)

1 evidences

A multicentre randomized trial found collagen meniscus implants supported new meniscus-like tissue growth and improved activity and reoperation rates in patients with chronic meniscal injury.

Trust comment: Large, multicentre randomized prospective trial with long follow-up and objective surgical/clinical endpoints.

Study Details

PMID:18594088
Participants:311
Impact:significantly fewer non-protocol reoperations vs control (p = 0.04)
Trust score:5/5

visual acuity (UDVA/CDVA)

1 evidences

In patients with keratoconus, intracorneal ring segments plus corneal collagen crosslinking improved corneal topography and vision substantially; concurrent versus sequential timing showed equivalent outcomes.

Trust comment: Large randomized clinical trial (198 patients) with objective refractive and visual outcomes and 6-month follow-up.

Study Details

PMID:30928252
Participants:198
Impact:UDVA improved by ~2.0 logMAR lines; CDVA improved by ~1.1 lines
Trust score:5/5

Spine BMD (PA and lateral)

1 evidences

Alendronate increased bone mineral density over 2.5 years; all subjects received calcium and vitamin D but the study did not test vitamin D effects.

Trust comment: Double-blind, placebo-controlled randomized clinical trial with clear outcome measures and adequate sample size.

Study Details

PMID:9738515
Participants:120
Impact:+7.8% (PA), +10.6% (lateral) (long-term increases)
Trust score:4/5

Urinary cross-linked collagen (N-telopeptide)

1 evidences

Alendronate increased bone mineral density over 2.5 years; all subjects received calcium and vitamin D but the study did not test vitamin D effects.

Trust comment: Double-blind, placebo-controlled randomized clinical trial with clear outcome measures and adequate sample size.

Study Details

PMID:9738515
Participants:120
Impact:-10% to -53% at 6 months (early decrease correlating with long-term BMD gains)
Trust score:4/5

skin firmness

2 evidences

A 90-day randomized trial found that ortho-silicic acid stabilized by hydrolyzed marine collagen improved skin firmness, hydration, and texture by clinical assessment.

Trust comment: Randomized, placebo-controlled trial but small sample (n=22) and objective imaging did not show statistical differences.

Study Details

PMID:28941141
Participants:22
Impact:improved (clinical evaluation statistically superior to placebo)
Trust score:3/5

Randomized double-blind vehicle-controlled 12-week trial of a topical firming/toning lotion (FTB) in 54 women showed significant improvements in skin firmness, texture, and cellulite and preclinical evidence of increased collagen and elastic fiber formation.

Trust comment: Randomized, double-blind, vehicle-controlled trial with objective instrumentation and preclinical histological/gene-expression support showing increases in collagen-related markers; moderate sample size.

Study Details

PMID:37683065
Participants:54
Impact:significant improvement vs baseline and vehicle at week 12
Trust score:4/5

Fistula formation

1 evidences

Using Alloderm (acellular dermal matrix) in hypospadias repair reduced postoperative fistula rates compared with standard repair.

Trust comment: Randomized controlled trial with a clear, clinically relevant endpoint and moderate sample size showing statistically significant benefit.

Study Details

PMID:34039476
Participants:60
Impact:10% (Alloderm) vs 26.7% (control); statistically lower with Alloderm (P = 0.014)
Trust score:4/5

Recurrence after fistula repair

1 evidences

Using Alloderm (acellular dermal matrix) in hypospadias repair reduced postoperative fistula rates compared with standard repair.

Trust comment: Randomized controlled trial with a clear, clinically relevant endpoint and moderate sample size showing statistically significant benefit.

Study Details

PMID:34039476
Participants:60
Impact:lower incidence in Alloderm group (1 vs 2 in controls reported)
Trust score:4/5

Post-operative complications

1 evidences

Using Alloderm (acellular dermal matrix) in hypospadias repair reduced postoperative fistula rates compared with standard repair.

Trust comment: Randomized controlled trial with a clear, clinically relevant endpoint and moderate sample size showing statistically significant benefit.

Study Details

PMID:34039476
Participants:60
Impact:no significant bleeding or diverticulum in either group
Trust score:4/5

Papillary height

1 evidences

Volume-stable collagen matrix was as effective as connective tissue graft for papilla reconstruction and caused less post-operative pain.

Trust comment: Randomized clinical trial with modest sample showing comparable efficacy and lower post-op pain for the collagen matrix.

Study Details

PMID:40199770
Participants:36
Impact:statistically significant gain from baseline to 6 months in both groups
Trust score:4/5

CP-TP distance (contact point to papilla tip)

1 evidences

Volume-stable collagen matrix was as effective as connective tissue graft for papilla reconstruction and caused less post-operative pain.

Trust comment: Randomized clinical trial with modest sample showing comparable efficacy and lower post-op pain for the collagen matrix.

Study Details

PMID:40199770
Participants:36
Impact:statistically significant reduction from baseline to 6 months in both groups
Trust score:4/5

Post-operative pain (VAS)

1 evidences

Volume-stable collagen matrix was as effective as connective tissue graft for papilla reconstruction and caused less post-operative pain.

Trust comment: Randomized clinical trial with modest sample showing comparable efficacy and lower post-op pain for the collagen matrix.

Study Details

PMID:40199770
Participants:36
Impact:lower in VCMX group vs SCTG (P = 0.044)
Trust score:4/5

Fibrinogen

1 evidences

Randomized comparison of femoral closure devices including AngioSeal (anchor + collagen sponge) showed no device-related differences in systemic inflammatory markers; IL-6 rose at 6 hours in all groups.

Trust comment: Randomized study with biomarker endpoints and adequate reporting showing no device-specific systemic inflammatory effect.

Study Details

PMID:18398639
Participants:77
Impact:no between-group change; no sustained increase at 30 days
Trust score:4/5

complete wound closure rate (6 months)

1 evidences

A skin graft product containing a collagen matrix helped long-standing venous leg ulcers heal faster and in more people than standard compression alone.

Trust comment: Randomized, prospective controlled trial with clear outcomes and reasonable sample size (n=120), supporting moderate-high trust.

Study Details

PMID:10781211
Participants:120
Impact:+28 percentage points (47% vs 19% healed with Graftskin vs control)
Trust score:4/5

likelihood of healing by 6 months

1 evidences

A skin graft product containing a collagen matrix helped long-standing venous leg ulcers heal faster and in more people than standard compression alone.

Trust comment: Randomized, prospective controlled trial with clear outcomes and reasonable sample size (n=120), supporting moderate-high trust.

Study Details

PMID:10781211
Participants:120
Impact:approximately 2x more likely (multivariate analysis, p < 0.005)
Trust score:4/5

radiographic bone level change (6 years)

1 evidences

At 6 years, using a resorbable collagen barrier gave similar bone levels and no more complications than a nonresorbable titanium-reinforced barrier.

Trust comment: Double-blind randomized design with long follow-up is strong, but very small sample (n=22) limits power and generalizability.

Study Details

PMID:25032771
Participants:22
Impact:no significant difference (mean 1.33 mm resorbable vs 1.00 mm nonresorbable; adjusted diff 0.15 mm, p = 0.5713)
Trust score:3/5

implant failures and complications

1 evidences

At 6 years, using a resorbable collagen barrier gave similar bone levels and no more complications than a nonresorbable titanium-reinforced barrier.

Trust comment: Double-blind randomized design with long follow-up is strong, but very small sample (n=22) limits power and generalizability.

Study Details

PMID:25032771
Participants:22
Impact:none reported after loading
Trust score:3/5

grip strength

1 evidences

Randomized, double-blind 24-week pilot trial in knee OA patients comparing HC-II (type II collagen hydrolysate), EC-HC-II (chicken essence + HC-II), glucosamine, and placebo; HC-II reduced early pain and EC-HC-II increased fat-free mass and grip strength versus some comparators.

Trust comment: Randomized, double-blind human trial directly testing type II collagen hydrolysate; pilot study with moderate sample size and some endpoints lacking detailed effect sizes.

Study Details

PMID:36918892
Participants:151
Impact:EC-HC-II: significantly greater grip strength at 24 weeks versus glucosamine (p=0.002)
Trust score:4/5

duration of drainage

2 evidences

Topical type I collagen powder showed a non-significant trend to less overall drainage; in patients with >10 nodes removed it significantly reduced lymphorrhea volume and duration.

Trust comment: Randomized controlled trial (n=80) with clinically relevant endpoints; subgroup benefit when >10 nodes removed but overall primary outcomes not significant.

Study Details

PMID:21614910
Participants:80
Impact:no overall difference; significantly shorter in subgroup with >10 nodes excised
Trust score:4/5

Randomized prospective single-center study testing a collagen-based sealant patch (TachoSil) versus standard care in RLND for melanoma; patch reduced drainage duration and increased % drainage-free at day 21.

Trust comment: Randomized prospective study with adequate sample (n=70) and significant primary endpoint, though single-center and potential center-specific practices.

Study Details

PMID:23253298
Participants:70
Impact:mean 20.1 vs 23.3 days (ITT); ~3.2 days shorter with collagen patch (P=0.010)
Trust score:4/5

drainage-free incidence at day 21

1 evidences

Randomized prospective single-center study testing a collagen-based sealant patch (TachoSil) versus standard care in RLND for melanoma; patch reduced drainage duration and increased % drainage-free at day 21.

Trust comment: Randomized prospective study with adequate sample (n=70) and significant primary endpoint, though single-center and potential center-specific practices.

Study Details

PMID:23253298
Participants:70
Impact:86% vs 67% (CSP vs standard); +19 percentage points (P=0.049)
Trust score:4/5

daily drainage volume (day 21)

1 evidences

Randomized prospective single-center study testing a collagen-based sealant patch (TachoSil) versus standard care in RLND for melanoma; patch reduced drainage duration and increased % drainage-free at day 21.

Trust comment: Randomized prospective study with adequate sample (n=70) and significant primary endpoint, though single-center and potential center-specific practices.

Study Details

PMID:23253298
Participants:70
Impact:trend lower with CSP (25.7 vs 39.7 cc), not statistically significant (P=0.058)
Trust score:4/5

lymphocele incidence

2 evidences

Randomized pilot study in endometrial cancer patients undergoing pelvic lymphadenectomy: application of a collagen patch (TachoSil) reduced lymphocele formation and symptomatic cases.

Trust comment: Randomized pilot trial (n=58) with clinically relevant endpoints but modest size and pilot design.

Study Details

PMID:21987409
Participants:58
Impact:7/30 vs 16/28 (TachoSil vs control); fewer lymphoceles with patch
Trust score:3/5

Use of a fibrinogen/coagulation-factor coated collagen patch (TachoSil) at lymphadenectomy sites was associated with lower drainage volume and fewer lymphoceles compared with historical controls.

Trust comment: Matched case-control with small sample and historical controls; suggests benefit but limited by non-randomized design.

Study Details

PMID:23574881
Participants:55
Impact:decreased (~19% vs ~52%; absolute −32 percentage points; 5/26 vs 15/29)
Trust score:3/5

symptomatic lymphoceles

2 evidences

Randomized pilot study in endometrial cancer patients undergoing pelvic lymphadenectomy: application of a collagen patch (TachoSil) reduced lymphocele formation and symptomatic cases.

Trust comment: Randomized pilot trial (n=58) with clinically relevant endpoints but modest size and pilot design.

Study Details

PMID:21987409
Participants:58
Impact:3 vs 9 (TachoSil vs control); fewer symptomatic cases with patch
Trust score:3/5

Use of a fibrinogen/coagulation-factor coated collagen patch (TachoSil) at lymphadenectomy sites was associated with lower drainage volume and fewer lymphoceles compared with historical controls.

Trust comment: Matched case-control with small sample and historical controls; suggests benefit but limited by non-randomized design.

Study Details

PMID:23574881
Participants:55
Impact:fewer symptomatic cases (2 vs 5; no statistical difference reported)
Trust score:3/5

need for percutaneous drainage

1 evidences

Randomized pilot study in endometrial cancer patients undergoing pelvic lymphadenectomy: application of a collagen patch (TachoSil) reduced lymphocele formation and symptomatic cases.

Trust comment: Randomized pilot trial (n=58) with clinically relevant endpoints but modest size and pilot design.

Study Details

PMID:21987409
Participants:58
Impact:1 vs 4 (TachoSil vs control)
Trust score:3/5

Gingival thickness (GT)

2 evidences

Porcine collagen matrix used with a tunnel technique reduced surgery time and morbidity but provided less complete root coverage than palatal connective tissue grafts; both improved gingival measures at 12 months.

Trust comment: Randomized split-mouth clinical trial with objective measurements but small sample size (22 patients).

Study Details

PMID:23627374
Participants:22
Impact:Test (CM): 0.8 ±0.2 → 1.0 ±0.3 mm (+0.2 mm); Control (CTG): 0.8 ±0.3 → 1.3 ±0.4 mm (+0.5 mm) (p<0.05)
Trust score:4/5

In PAOO patients, collagen barrier membrane (control) increased gingival thickness modestly at 6 months, but CGF membrane produced a larger increase; both groups showed bone parameter changes.

Trust comment: Randomized controlled trial directly comparing a collagen barrier membrane (control) to CGF membrane with objective CBCT measures and 6-month follow-up; single-center and modest sample size limit external generalizability.

Study Details

PMID:34814921
Participants:40
Impact:control (collagen membrane) increased from 0.94±0.19 to 1.02±0.16 mm at 6 months (+0.08 mm); CGF increased to 1.31±0.33 mm (+0.37 mm); intergroup p<0.01
Trust score:4/5

Patient morbidity / duration of surgery

1 evidences

Porcine collagen matrix used with a tunnel technique reduced surgery time and morbidity but provided less complete root coverage than palatal connective tissue grafts; both improved gingival measures at 12 months.

Trust comment: Randomized split-mouth clinical trial with objective measurements but small sample size (22 patients).

Study Details

PMID:23627374
Participants:22
Impact:Reduced with collagen matrix versus connective tissue graft (p<0.05)
Trust score:4/5

wound closure

1 evidences

A collagen-laminin dermal matrix (Dermalix) accelerated wound closure and reduced oxidative stress markers versus standard wound care in Wagner 1–2 diabetic foot ulcers over 4 weeks.

Trust comment: Prospective randomized comparative clinical device study (n=48) with biochemical and clinical endpoints; open-label which may introduce bias.

Study Details

PMID:32131656
Participants:48
Impact:Dx 57.82% vs SWC 26.63% at 4 weeks (≈2-fold faster closure)
Trust score:4/5

Inflammation / apoptosis markers

1 evidences

A collagen-laminin dermal matrix (Dermalix) accelerated wound closure and reduced oxidative stress markers versus standard wound care in Wagner 1–2 diabetic foot ulcers over 4 weeks.

Trust comment: Prospective randomized comparative clinical device study (n=48) with biochemical and clinical endpoints; open-label which may introduce bias.

Study Details

PMID:32131656
Participants:48
Impact:Decreased TNF and caspase-3 levels (statistically significant)
Trust score:4/5

Oxidative stress (GSH/GSSG)

1 evidences

A collagen-laminin dermal matrix (Dermalix) accelerated wound closure and reduced oxidative stress markers versus standard wound care in Wagner 1–2 diabetic foot ulcers over 4 weeks.

Trust comment: Prospective randomized comparative clinical device study (n=48) with biochemical and clinical endpoints; open-label which may introduce bias.

Study Details

PMID:32131656
Participants:48
Impact:Improved reduced/oxidized glutathione ratio and decreased lipid peroxidation (statistically significant)
Trust score:4/5

Anti-BP180 IgG level

1 evidences

In bullous pemphigoid patients, higher IgG autoantibodies against BP180 (a noncollagenous domain of type XVII collagen) were associated with lower functional status and higher 1-year mortality.

Trust comment: Large prospective serological substudy (n=143) nested in a randomized trial; associations observational but clinically relevant.

Study Details

PMID:29607480
Participants:143
Impact:Higher levels associated with increased 1-year mortality
Trust score:4/5

Karnofsky score

1 evidences

In bullous pemphigoid patients, higher IgG autoantibodies against BP180 (a noncollagenous domain of type XVII collagen) were associated with lower functional status and higher 1-year mortality.

Trust comment: Large prospective serological substudy (n=143) nested in a randomized trial; associations observational but clinically relevant.

Study Details

PMID:29607480
Participants:143
Impact:High anti-BP180 and anti-BP230 IgG associated with lower Karnofsky scores
Trust score:4/5

Adverse events profile

1 evidences

In bullous pemphigoid patients, higher IgG autoantibodies against BP180 (a noncollagenous domain of type XVII collagen) were associated with lower functional status and higher 1-year mortality.

Trust comment: Large prospective serological substudy (n=143) nested in a randomized trial; associations observational but clinically relevant.

Study Details

PMID:29607480
Participants:143
Impact:Higher total IgE associated with fewer adverse events (reported association)
Trust score:4/5

Topographic inferior–superior (I–S) difference

1 evidences

In patients with keratoconus, intracorneal ring segments plus corneal collagen crosslinking improved corneal topography and vision substantially; concurrent versus sequential timing showed equivalent outcomes.

Trust comment: Large randomized clinical trial (198 patients) with objective refractive and visual outcomes and 6-month follow-up.

Study Details

PMID:30928252
Participants:198
Impact:Improved by 3.9 D
Trust score:5/5

Serum collagen level

1 evidences

In chronic hepatitis C patients, drinking 4 cups of coffee/day reduced markers of oxidative damage and serum collagen levels, and increased telomere length versus abstinence over 30 days.

Trust comment: Randomized crossover trial (n=40) with biochemical endpoints; modest size but randomized design supports findings.

Study Details

PMID:23238034
Participants:40
Impact:Decreased: 56 ± 9 vs 86 ± 21 ng/mL during coffee vs abstinence (p=0.04)
Trust score:4/5

8-hydroxydeoxyguanosine (oxidative DNA damage)

1 evidences

In chronic hepatitis C patients, drinking 4 cups of coffee/day reduced markers of oxidative damage and serum collagen levels, and increased telomere length versus abstinence over 30 days.

Trust comment: Randomized crossover trial (n=40) with biochemical endpoints; modest size but randomized design supports findings.

Study Details

PMID:23238034
Participants:40
Impact:Decreased: 15 ± 3 vs 44 ± 16 per 10^5 deoxyguanosine during coffee vs abstinence (p=0.05)
Trust score:4/5

Telomere length

1 evidences

In chronic hepatitis C patients, drinking 4 cups of coffee/day reduced markers of oxidative damage and serum collagen levels, and increased telomere length versus abstinence over 30 days.

Trust comment: Randomized crossover trial (n=40) with biochemical endpoints; modest size but randomized design supports findings.

Study Details

PMID:23238034
Participants:40
Impact:Increased during coffee intake (0.68 ± 0.06 vs 0.48 ± 0.04 AU; p=0.006)
Trust score:4/5

goblet cell density (superior conjunctiva)

1 evidences

Corneal cross-linking reduced goblet cell density on the superior conjunctiva; topical riboflavin improved epithelial cell morphology in another group, with no difference in total scores between groups.

Trust comment: Controlled clinical comparison on human eyes with simple cytologic endpoints; moderate sample size and short follow-up.

Study Details

PMID:20622670
Participants:40
Impact:decreased after corneal collagen cross-linking (P=0.008)
Trust score:3/5

epithelial cell morphology (temporal conjunctiva)

1 evidences

Corneal cross-linking reduced goblet cell density on the superior conjunctiva; topical riboflavin improved epithelial cell morphology in another group, with no difference in total scores between groups.

Trust comment: Controlled clinical comparison on human eyes with simple cytologic endpoints; moderate sample size and short follow-up.

Study Details

PMID:20622670
Participants:40
Impact:improved with topical riboflavin (better cell-to-cell contact, P=0.003; reduced keratinization, P=0.034)
Trust score:3/5

total impression cytology score

1 evidences

Corneal cross-linking reduced goblet cell density on the superior conjunctiva; topical riboflavin improved epithelial cell morphology in another group, with no difference in total scores between groups.

Trust comment: Controlled clinical comparison on human eyes with simple cytologic endpoints; moderate sample size and short follow-up.

Study Details

PMID:20622670
Participants:40
Impact:no difference between groups after treatment
Trust score:3/5

mature cross-link HHL

1 evidences

Six months of oestradiol in postmenopausal women decreased total vaginal collagen and markers of aged collagen while increasing immature cross-links and MMP-2 expression, indicating stimulated collagen turnover.

Trust comment: Double-blind placebo-controlled biopsy study with clear biochemical endpoints and good completion rate (49 of 55), providing reliable evidence on collagen metabolism.

Study Details

PMID:11950190
Participants:49
Impact:decreased with oestradiol (P=0.0009)
Trust score:4/5

immature cross-link HLKNL and MMP-2 expression

1 evidences

Six months of oestradiol in postmenopausal women decreased total vaginal collagen and markers of aged collagen while increasing immature cross-links and MMP-2 expression, indicating stimulated collagen turnover.

Trust comment: Double-blind placebo-controlled biopsy study with clear biochemical endpoints and good completion rate (49 of 55), providing reliable evidence on collagen metabolism.

Study Details

PMID:11950190
Participants:49
Impact:HLKNL increased (P=0.0191); Pro-MMP-2 increased (P=0.0017)
Trust score:4/5

successful topical hemostasis rate (≤10 min)

1 evidences

Two collagen-based topical hemostatic sponges achieved similar rates of hemostasis during cardiothoracic surgery; one had better handling characteristics.

Trust comment: Prospective randomized clinical trial in surgical patients with a practical endpoint; moderate size but industry product comparison limits generalizability.

Study Details

PMID:10327079
Participants:60
Impact:Hemostagene 75% vs Helistat 77% (no significant difference)
Trust score:3/5

handling characteristics

1 evidences

Two collagen-based topical hemostatic sponges achieved similar rates of hemostasis during cardiothoracic surgery; one had better handling characteristics.

Trust comment: Prospective randomized clinical trial in surgical patients with a practical endpoint; moderate size but industry product comparison limits generalizability.

Study Details

PMID:10327079
Participants:60
Impact:Hemostagene rated easier to handle
Trust score:3/5

maximum keratometry (max K)

1 evidences

Corneal collagen crosslinking improved vision and corneal curvature over one year versus sham (riboflavin alone), with many patients gaining lines of vision and mean K values decreasing.

Trust comment: Prospective randomized controlled trial with a sham control and reasonable sample size; well-reported clinical outcomes.

Study Details

PMID:21183110
Participants:71
Impact:decrease of 1.7 ± 3.9 D overall (P < .001); keratoconus subgroup −2.0 ± 4.4 D (P = .002)
Trust score:4/5

perineal wound complications

1 evidences

Local gentamicin–collagen applied during abdominoperineal resection did not reduce perineal wound complications nor change cancer recurrence rates.

Trust comment: Multicentre randomized controlled trial (n=102) directly tested a gentamicin–collagen product with adequate follow-up.

Study Details

PMID:22889358
Participants:102
Impact:no statistically significant difference vs control
Trust score:4/5

cancer recurrence

1 evidences

Local gentamicin–collagen applied during abdominoperineal resection did not reduce perineal wound complications nor change cancer recurrence rates.

Trust comment: Multicentre randomized controlled trial (n=102) directly tested a gentamicin–collagen product with adequate follow-up.

Study Details

PMID:22889358
Participants:102
Impact:no statistically significant difference vs control
Trust score:4/5

collagen III expression

1 evidences

31 renal-allograft recipients randomized to cyclosporine reduction with or without rapamycin; rapamycin group had a fall in GFR and increases in collagen III expression and TIMP-2 without histological improvement in interstitial fibrosis.

Trust comment: Small randomized trial that directly measured collagen III expression and histological fibrosis; limited sample size and short follow-up reduce confidence but outcomes are directly collagen-related.

Study Details

PMID:12660500
Participants:31
Impact:increased over 6 months in rapamycin patients
Trust score:3/5

skin sagging (Ezure scale)

1 evidences

Mechanical skin stimulation produced clinically improved radiance/relief and increased fibroblast migration and MMP-9 synthesis, with a trend toward improved sagging.

Trust comment: Randomized, double-blinded controlled trial (n=30) with clinical, histologic, and biochemical endpoints showing consistent signals though sample size is moderate.

Study Details

PMID:25673979
Participants:30
Impact:improvement in 73% treated vs 53% control (P=0.108) — trend, not statistically significant
Trust score:4/5

skin radiance/color scores

1 evidences

Mechanical skin stimulation produced clinically improved radiance/relief and increased fibroblast migration and MMP-9 synthesis, with a trend toward improved sagging.

Trust comment: Randomized, double-blinded controlled trial (n=30) with clinical, histologic, and biochemical endpoints showing consistent signals though sample size is moderate.

Study Details

PMID:25673979
Participants:30
Impact:significant improvement on treated side vs control (P<0.05)
Trust score:4/5

MMP-9 synthesis

1 evidences

Mechanical skin stimulation produced clinically improved radiance/relief and increased fibroblast migration and MMP-9 synthesis, with a trend toward improved sagging.

Trust comment: Randomized, double-blinded controlled trial (n=30) with clinical, histologic, and biochemical endpoints showing consistent signals though sample size is moderate.

Study Details

PMID:25673979
Participants:30
Impact:significant increase (+115.4%, P<0.05)
Trust score:4/5

uncorrected distance visual acuity

2 evidences

At 4 years, standard corneal cross-linking produced greater anterior corneal flattening than accelerated CXL (especially for peripheral cones); differences in visual acuity were not statistically significant.

Trust comment: Randomized clinical trial with 4-year follow-up (62 eyes) reporting robust long-term topographic and clinical outcomes; relevant to corneal collagen biomechanics.

Study Details

PMID:30943777
Participants:62
Impact:improvement: standard 0.19±0.30 vs accelerated 0.08±0.35 logMAR (not significant, p=0.283)
Trust score:4/5

Adding transepithelial corneal collagen cross-linking to intracorneal ring surgery improved vision and reduced spherical refractive error more than ring surgery alone.

Trust comment: Randomized study but small sample (29 patients, 40 eyes) with short-term follow-up reported; methods acceptable but limited power.

Study Details

PMID:26356750
Participants:29
Impact:statistically significant improvement
Trust score:3/5

anterior Kmax-3 mm reduction

1 evidences

At 4 years, standard corneal cross-linking produced greater anterior corneal flattening than accelerated CXL (especially for peripheral cones); differences in visual acuity were not statistically significant.

Trust comment: Randomized clinical trial with 4-year follow-up (62 eyes) reporting robust long-term topographic and clinical outcomes; relevant to corneal collagen biomechanics.

Study Details

PMID:30943777
Participants:62
Impact:standard −1.35±1.39 D vs accelerated −0.36±1.10 D (p=0.011)
Trust score:4/5

anterior Kmax-8 mm reduction

1 evidences

At 4 years, standard corneal cross-linking produced greater anterior corneal flattening than accelerated CXL (especially for peripheral cones); differences in visual acuity were not statistically significant.

Trust comment: Randomized clinical trial with 4-year follow-up (62 eyes) reporting robust long-term topographic and clinical outcomes; relevant to corneal collagen biomechanics.

Study Details

PMID:30943777
Participants:62
Impact:standard −1.50±1.82 D vs accelerated −0.37±1.58 D (p=0.029)
Trust score:4/5

pad loss (quantified pad test)

1 evidences

Permacol (porcine dermal collagen) injections improved urinary stress incontinence measures more than Macroplastique, with effects sustained to 6 months.

Trust comment: Randomized prospective trial with 6-month follow-up but small sample (n=50) and relatively short follow-up, limiting generalizability.

Study Details

PMID:15378234
Participants:50
Impact:Permacol: 64% improved; 60% dry at 6 weeks vs Macroplastique: 54% improved; 41.6% dry (Permacol sustained at 6 months; Macroplastique not sustained)
Trust score:3/5

Stamey score (subjective incontinence grade)

1 evidences

Permacol (porcine dermal collagen) injections improved urinary stress incontinence measures more than Macroplastique, with effects sustained to 6 months.

Trust comment: Randomized prospective trial with 6-month follow-up but small sample (n=50) and relatively short follow-up, limiting generalizability.

Study Details

PMID:15378234
Participants:50
Impact:Permacol: 64% reduction at 6 weeks vs Macroplastique: 46% reduction
Trust score:3/5

King's College Quality (KCQ) score

1 evidences

Permacol (porcine dermal collagen) injections improved urinary stress incontinence measures more than Macroplastique, with effects sustained to 6 months.

Trust comment: Randomized prospective trial with 6-month follow-up but small sample (n=50) and relatively short follow-up, limiting generalizability.

Study Details

PMID:15378234
Participants:50
Impact:Permacol: 60% reduction at 6 weeks vs Macroplastique: 42% reduction; Permacol maintained at 6 months
Trust score:3/5

crestal ridge width

1 evidences

Using two types of xenogeneic collagen matrices with bone graft helped maintain soft tissues and limited ridge resorption after tooth extraction, with small increases in gingival thickness.

Trust comment: Randomized controlled prospective study but very small completed sample (n=23), reducing precision and external validity.

Study Details

PMID:26745614
Participants:23
Impact:reduction of −1.8 mm (CM) and −2.0 mm (ECM); differences between matrices not significant)
Trust score:3/5

facial wrinkle severity (including crow's feet)

1 evidences

A 12-week oral chicken sternal cartilage (BioCell Collagen) supplement increased skin collagen and elasticity and reduced wrinkle severity versus placebo.

Trust comment: Well-designed double-blind placebo-controlled RCT with objective measures and 113 completers, though industry/product-specific formulation may limit independent replication.

Study Details

PMID:31221944
Participants:113
Impact:significant reduction (facial lines P=.019; crow's feet P=.05)
Trust score:4/5

cutaneous collagen content

1 evidences

A 12-week oral chicken sternal cartilage (BioCell Collagen) supplement increased skin collagen and elasticity and reduced wrinkle severity versus placebo.

Trust comment: Well-designed double-blind placebo-controlled RCT with objective measures and 113 completers, though industry/product-specific formulation may limit independent replication.

Study Details

PMID:31221944
Participants:113
Impact:increased by 12% (P<.001)
Trust score:4/5

Patient-rated voice improvement

1 evidences

Randomized trial comparing hylan B gel vs bovine cross-linked collagen injections for glottal insufficiency showed both improved voice and glottal closure; collagen showed more resorption/trend to more loss.

Trust comment: Direct randomized clinical comparison of collagen injections with moderate sample size and 2-year follow-up but with substantial dropout, limiting strength.

Study Details

PMID:15768820
Participants:70
Impact:significant improvement in both groups
Trust score:3/5

Resorption at injected vocal fold edge

1 evidences

Randomized trial comparing hylan B gel vs bovine cross-linked collagen injections for glottal insufficiency showed both improved voice and glottal closure; collagen showed more resorption/trend to more loss.

Trust comment: Direct randomized clinical comparison of collagen injections with moderate sample size and 2-year follow-up but with substantial dropout, limiting strength.

Study Details

PMID:15768820
Participants:70
Impact:greater for collagen (trend, p=0.05)
Trust score:3/5

procollagen type I (PINP)

1 evidences

Two weeks of calf intermittent pneumatic compression (IPC) during immobilization markedly increased markers of collagen type I production in healing Achilles tendons but did not change clinical outcomes at 3 or 12 months.

Trust comment: Randomized, single-blind controlled trial with clear biomarker endpoints (microdialysis) though collagen marker analysis used a modest subset (n=14 vs n=19).

Study Details

PMID:28668970
Participants:33
Impact:+69% in healing Achilles tendon (IPC vs plaster cast); +49% in intact AT (IPC vs control)
Trust score:4/5

procollagen type III (PIIINP)

1 evidences

Two weeks of calf intermittent pneumatic compression (IPC) during immobilization markedly increased markers of collagen type I production in healing Achilles tendons but did not change clinical outcomes at 3 or 12 months.

Trust comment: Randomized, single-blind controlled trial with clear biomarker endpoints (microdialysis) though collagen marker analysis used a modest subset (n=14 vs n=19).

Study Details

PMID:28668970
Participants:33
Impact:no significant difference between groups
Trust score:4/5

patient-reported/functional outcomes

1 evidences

Two weeks of calf intermittent pneumatic compression (IPC) during immobilization markedly increased markers of collagen type I production in healing Achilles tendons but did not change clinical outcomes at 3 or 12 months.

Trust comment: Randomized, single-blind controlled trial with clear biomarker endpoints (microdialysis) though collagen marker analysis used a modest subset (n=14 vs n=19).

Study Details

PMID:28668970
Participants:33
Impact:no significant difference at 3 and 12 months
Trust score:4/5

P1NP (procollagen type I N-terminal propeptide)

2 evidences

Small randomized study in postmenopausal osteopenic women: adding bioactive collagen peptides to calcium+vitamin D lowered bone turnover markers over 3 months compared with calcium+vitamin D alone.

Trust comment: Randomized prospective study with objective biochemical endpoints but modest sample size and short (3-month) follow-up limiting longer-term conclusions.

Study Details

PMID:32131366
Participants:43
Impact:-13.1% within collagen-peptide group; between-groups % change -13.1% vs -2.1% (p=0.011)
Trust score:3/5

In 45 postmenopausal osteopenic women, a 12-week supervised walking program improved function and increased bone turnover markers (P1NP, CTX) with osteocalcin rising in the exercise group; both groups received vitamin D and calcium.

Trust comment: Randomized controlled single-blind trial with objective laboratory outcomes; confounded by universal vitamin D/calcium supplementation and modest sample size.

Study Details

PMID:40259282
Participants:45
Impact:Increased +168.2 ng/ml (exercise group 0→12w; p<0.001); increased +156.2 ng/ml (control; p<0.001)
Trust score:4/5

CTX (C-terminal telopeptide of collagen I)

1 evidences

Small randomized study in postmenopausal osteopenic women: adding bioactive collagen peptides to calcium+vitamin D lowered bone turnover markers over 3 months compared with calcium+vitamin D alone.

Trust comment: Randomized prospective study with objective biochemical endpoints but modest sample size and short (3-month) follow-up limiting longer-term conclusions.

Study Details

PMID:32131366
Participants:43
Impact:-11.4% within collagen-peptide group (trend, p=0.058); between-groups p=0.079
Trust score:3/5

collagen production (dermal fibroblasts)

1 evidences

A designed tetrapeptide (GEKG) increased collagen production in vitro and showed significant reduction in skin roughness (wrinkles) in a 30-participant clinical evaluation.

Trust comment: Randomized, placebo-controlled clinical assessments with objective wrinkle measurement but small sample sizes (n=10 pilot for molecular in vivo; n=30 for wrinkle assessment).

Study Details

PMID:21692860
Participants:30
Impact:increased at mRNA and protein levels (in vitro and in vivo pilot n=10)
Trust score:3/5

skin roughness (wrinkles)

1 evidences

A designed tetrapeptide (GEKG) increased collagen production in vitro and showed significant reduction in skin roughness (wrinkles) in a 30-participant clinical evaluation.

Trust comment: Randomized, placebo-controlled clinical assessments with objective wrinkle measurement but small sample sizes (n=10 pilot for molecular in vivo; n=30 for wrinkle assessment).

Study Details

PMID:21692860
Participants:30
Impact:significant decrease vs placebo in 30 volunteers (3D surface roughness)
Trust score:3/5

β-CTX-I (bone resorption marker)

1 evidences

4-year randomized trial (SONIA 2) in alkaptonuria patients showing nitisinone alters trajectories of type I (bone) and type II (cartilage) collagen turnover biomarkers.

Trust comment: Large multicentre randomized controlled study with long follow-up and appropriate biomarker analyses, though open-label and no placebo limit blinding.

Study Details

PMID:37446173
Participants:138
Impact:+19% at 1 year in nitisinone-treated patients vs controls (95% CI 5–36%) then returned to control levels
Trust score:4/5

PTH

1 evidences

In postmenopausal volunteers with low vitamin D, oral calcium produced marked suppression of bone resorption marker CTX (greater than vitamin D alone); vitamin D alone raised serum 25OHD but had smaller CTX effects.

Trust comment: Small randomized crossover human study with clear biomarker measurements but limited sample size.

Study Details

PMID:20349229
Participants:22
Impact:suppressed similarly by calcium and vitamin D
Trust score:3/5

implant stability (Periotest)

1 evidences

Compared salivary CTXI and implant stability (Periotest) in 40 patients randomized to early vs delayed implant loading; CTXI was essentially undetectable while early loading showed improved mechanical stability at 1 month.

Trust comment: Randomized controlled single-center study with clear endpoints but small sample and biomarker (salivary CTXI) largely undetectable, limiting biomarker conclusions.

Study Details

PMID:40604796
Participants:40
Impact:median decreased from 1.50 to 0.00 (−1.50 units) in early group; p=0.023 (improved stability)
Trust score:3/5

salivary CTXI (C-terminal telopeptide of type I collagen)

1 evidences

Compared salivary CTXI and implant stability (Periotest) in 40 patients randomized to early vs delayed implant loading; CTXI was essentially undetectable while early loading showed improved mechanical stability at 1 month.

Trust comment: Randomized controlled single-center study with clear endpoints but small sample and biomarker (salivary CTXI) largely undetectable, limiting biomarker conclusions.

Study Details

PMID:40604796
Participants:40
Impact:undetectable/very low; early median −1.42→−1.49 (p=0.23, ns); delayed −1.45→−1.43 (p=0.03 minimal change)
Trust score:3/5

skin hydration (face)

1 evidences

Randomized double-blind placebo-controlled trial (72 women) of daily 5 g tuna collagen peptides for 8 weeks: improved skin hydration, reduced TEWL, increased elasticity and skin density versus placebo; effects partly sustained 2 weeks after stopping.

Trust comment: Well-designed randomized double-blind placebo-controlled trial with complete follow-up (n=72); industry funding declared but investigators report no conflicts; moderate-to-high internal validity.

Study Details

PMID:39075819
Participants:72
Impact:increased from 47.6 to 72.6 A.U. at 8 weeks (+25.0 A.U.; relative +68.2% vs baseline); significant vs placebo
Trust score:4/5

transepidermal water loss (TEWL, face)

1 evidences

Randomized double-blind placebo-controlled trial (72 women) of daily 5 g tuna collagen peptides for 8 weeks: improved skin hydration, reduced TEWL, increased elasticity and skin density versus placebo; effects partly sustained 2 weeks after stopping.

Trust comment: Well-designed randomized double-blind placebo-controlled trial with complete follow-up (n=72); industry funding declared but investigators report no conflicts; moderate-to-high internal validity.

Study Details

PMID:39075819
Participants:72
Impact:relative change −10.4% at 8 weeks (reduced TEWL vs baseline; improved barrier)
Trust score:4/5

skin elasticity (VE, face)

1 evidences

Randomized double-blind placebo-controlled trial (72 women) of daily 5 g tuna collagen peptides for 8 weeks: improved skin hydration, reduced TEWL, increased elasticity and skin density versus placebo; effects partly sustained 2 weeks after stopping.

Trust comment: Well-designed randomized double-blind placebo-controlled trial with complete follow-up (n=72); industry funding declared but investigators report no conflicts; moderate-to-high internal validity.

Study Details

PMID:39075819
Participants:72
Impact:increased from 4.8 to 5.2 MPa at 8 weeks (relative +16.2% vs baseline); significant vs placebo
Trust score:4/5

Corrected distance visual acuity (CDVA) improvement (≥2 lines)

1 evidences

Cohort study of corneal collagen crosslinking (CXL) finding that worse preoperative vision and higher maximum K predict greater improvement after CXL.

Trust comment: Reasonable-sized clinical cohort directly addressing a collagen-targeted ophthalmic procedure (CXL); observational design and using eyes as units limit causal strength.

Study Details

PMID:23889865
Participants:104
Impact:OR 5.9 if preoperative CDVA 20/40 or worse
Trust score:3/5

Topographic flattening (max K decrease ≥2.0 D)

1 evidences

Cohort study of corneal collagen crosslinking (CXL) finding that worse preoperative vision and higher maximum K predict greater improvement after CXL.

Trust comment: Reasonable-sized clinical cohort directly addressing a collagen-targeted ophthalmic procedure (CXL); observational design and using eyes as units limit causal strength.

Study Details

PMID:23889865
Participants:104
Impact:OR 5.4 if preoperative maximum K ≥55.0 D
Trust score:3/5

Worsening of visual acuity/topography

1 evidences

Cohort study of corneal collagen crosslinking (CXL) finding that worse preoperative vision and higher maximum K predict greater improvement after CXL.

Trust comment: Reasonable-sized clinical cohort directly addressing a collagen-targeted ophthalmic procedure (CXL); observational design and using eyes as units limit causal strength.

Study Details

PMID:23889865
Participants:104
Impact:no preoperative characteristics significantly predicted worsening
Trust score:3/5

Serum C-terminal telopeptide of type I collagen (CTX)

1 evidences

Randomized feeding study: the DASH diet lowered bone turnover markers and sodium reduction decreased calcium excretion and some bone markers; vitamin D was discussed but not tested.

Trust comment: Large randomized feeding study with controlled diets and clear biomarker changes; shows dietary effects on collagen-derived bone turnover markers (high trust for biomarker outcomes).

Study Details

PMID:14519796
Participants:186
Impact:-16% to -18% on DASH diet (P<0.001)
Trust score:4/5

PRO-C1 (type I collagen formation)

1 evidences

4-year randomized trial (SONIA 2) in alkaptonuria patients showing nitisinone alters trajectories of type I (bone) and type II (cartilage) collagen turnover biomarkers.

Trust comment: Large multicentre randomized controlled study with long follow-up and appropriate biomarker analyses, though open-label and no placebo limit blinding.

Study Details

PMID:37446173
Participants:138
Impact:+40% at 1 year in treated patients vs controls (95% CI 19–65%) then returned to control levels
Trust score:4/5

CTX-II/Creat (urine; cartilage remodelling)

1 evidences

4-year randomized trial (SONIA 2) in alkaptonuria patients showing nitisinone alters trajectories of type I (bone) and type II (cartilage) collagen turnover biomarkers.

Trust comment: Large multicentre randomized controlled study with long follow-up and appropriate biomarker analyses, though open-label and no placebo limit blinding.

Study Details

PMID:37446173
Participants:138
Impact:suppressed by ~27% at Year 3 and ~26% at Year 4 in treated patients vs controls
Trust score:4/5

corrected distance visual acuity

1 evidences

PACK-CXL added to antimicrobials did not shorten healing time but had fewer serious complications (no perforations or recurrences) than antimicrobials alone.

Trust comment: Prospective clinical trial with modest sample size; unclear randomization and some baseline differences limit strength.

Study Details

PMID:24576886
Participants:40
Impact:-0.03 (1.64 vs 1.67; no significant change, P = 0.68)
Trust score:3/5

complication rate (corneal perforation/recurrence)

1 evidences

PACK-CXL added to antimicrobials did not shorten healing time but had fewer serious complications (no perforations or recurrences) than antimicrobials alone.

Trust comment: Prospective clinical trial with modest sample size; unclear randomization and some baseline differences limit strength.

Study Details

PMID:24576886
Participants:40
Impact:-21 percentage points (0% PACK-CXL vs 21% control; fewer perforations/recurrences with PACK-CXL)
Trust score:3/5

radiographic defect bone level (DBL) gain

1 evidences

L-PRF+IBB was non-inferior to collagen membrane+IBB for clinical attachment gain and produced less gingival recession, though it had slightly less probing-depth reduction.

Trust comment: Randomized non-inferiority trial with balanced groups and 12-month follow-up; results reported with CIs.

Study Details

PMID:33547808
Participants:62
Impact:+0.65 mm (CM+IBB - L-PRF+IBB = -0.648 mm, favoring L-PRF+IBB)
Trust score:4/5

6-minute walk distance

1 evidences

Eplerenone did not improve exercise capacity but significantly reduced serum markers of collagen turnover and improved diastolic function.

Trust comment: Randomized, double-blind, placebo-controlled trial but small sample size limits precision.

Study Details

PMID:21807324
Participants:44
Impact:no change (similar improvements in eplerenone and placebo; P = .91)
Trust score:4/5

procollagen type I aminoterminal peptide

1 evidences

Eplerenone did not improve exercise capacity but significantly reduced serum markers of collagen turnover and improved diastolic function.

Trust comment: Randomized, double-blind, placebo-controlled trial but small sample size limits precision.

Study Details

PMID:21807324
Participants:44
Impact:significant decrease (P = .009)
Trust score:4/5

carboxy-terminal telopeptide of collagen type I

1 evidences

Eplerenone did not improve exercise capacity but significantly reduced serum markers of collagen turnover and improved diastolic function.

Trust comment: Randomized, double-blind, placebo-controlled trial but small sample size limits precision.

Study Details

PMID:21807324
Participants:44
Impact:significant decrease (P = .026)
Trust score:4/5

diastolic function (E/E')

1 evidences

Eplerenone did not improve exercise capacity but significantly reduced serum markers of collagen turnover and improved diastolic function.

Trust comment: Randomized, double-blind, placebo-controlled trial but small sample size limits precision.

Study Details

PMID:21807324
Participants:44
Impact:improved (P = .01)
Trust score:4/5

insulin-like growth factor I (IGF-I)

1 evidences

MK-677 raised IGF-I and bone-turnover markers and, when combined with alendronate, lessened alendronate's suppression of bone formation and increased femoral neck BMD more than alendronate alone.

Trust comment: Large multicenter randomized double-blind placebo-controlled study with long follow-up, though some site-specific effects noted.

Study Details

PMID:11238495
Participants:292
Impact:+39% to +45% (increase vs baseline; P < 0.05)
Trust score:4/5

urinary N-telopeptide cross-links (NTx)

1 evidences

MK-677 raised IGF-I and bone-turnover markers and, when combined with alendronate, lessened alendronate's suppression of bone formation and increased femoral neck BMD more than alendronate alone.

Trust comment: Large multicenter randomized double-blind placebo-controlled study with long follow-up, though some site-specific effects noted.

Study Details

PMID:11238495
Participants:292
Impact:+41% (increase with MK-677 vs baseline) and combination mitigated alendronate suppression (-52% vs -61%)
Trust score:4/5

femoral neck bone mineral density (BMD)

3 evidences

In renal transplant recipients, adding alendronate to calcium and calcitriol increased femoral neck BMD and decreased bone resorption marker NTx versus calcium+calcitriol alone in the short term.

Trust comment: Randomized clinical comparison but small sample and short-term follow-up limit generalizability.

Study Details

PMID:19100422
Participants:46
Impact:significant increase (P < .05) with alendronate vs control
Trust score:3/5

Pyridoxamine tended to raise a bone formation marker, increased femoral neck BMD, and slightly lowered HbA1c in older women with T2D.

Trust comment: Double-blind RCT with modest sample size showing significant BMD and HbA1c changes, though some outcomes are borderline.

Study Details

PMID:39376018
Participants:55
Impact:+2.6% with PM vs -0.9% placebo (between-groups P=0.007)
Trust score:4/5

MK-677 raised IGF-I and bone-turnover markers and, when combined with alendronate, lessened alendronate's suppression of bone formation and increased femoral neck BMD more than alendronate alone.

Trust comment: Large multicenter randomized double-blind placebo-controlled study with long follow-up, though some site-specific effects noted.

Study Details

PMID:11238495
Participants:292
Impact:+4.2% (MK-677 + alendronate) vs +2.5% (alendronate alone); P < 0.05
Trust score:4/5

lumbar spine BMD (L2-L4)

1 evidences

Transdermal estradiol+levonorgestrel increased BMD (lumbar spine, hip, total body) and reduced bone turnover markers over 2 years.

Trust comment: Prospective 2-year study with adequate sample size and consistent biomarker and BMD changes; well-reported safety data.

Study Details

PMID:15653003
Participants:212
Impact:+8% (increase vs placebo; P < 0.001)
Trust score:4/5

urinary CrossLaps (uCTX)

1 evidences

Transdermal estradiol+levonorgestrel increased BMD (lumbar spine, hip, total body) and reduced bone turnover markers over 2 years.

Trust comment: Prospective 2-year study with adequate sample size and consistent biomarker and BMD changes; well-reported safety data.

Study Details

PMID:15653003
Participants:212
Impact:-65% (decrease from baseline; P < 0.001)
Trust score:4/5

anterior corneal total HOAs

1 evidences

Corneal collagen crosslinking significantly reduced corneal and ocular higher-order aberrations at 1 year, suggesting improved corneal shape.

Trust comment: Prospective randomized controlled clinical trial with objective imaging outcomes and decent sample size (eyes and fellow-eye controls).

Study Details

PMID:22322165
Participants:73
Impact:decrease of -0.41 μm (4.68 → 4.27 μm; -8.8%; P < .001)
Trust score:4/5

anterior corneal total coma

1 evidences

Corneal collagen crosslinking significantly reduced corneal and ocular higher-order aberrations at 1 year, suggesting improved corneal shape.

Trust comment: Prospective randomized controlled clinical trial with objective imaging outcomes and decent sample size (eyes and fellow-eye controls).

Study Details

PMID:22322165
Participants:73
Impact:decrease of -0.39 μm (4.40 → 4.01 μm; P < .001)
Trust score:4/5

total ocular HOAs

1 evidences

Corneal collagen crosslinking significantly reduced corneal and ocular higher-order aberrations at 1 year, suggesting improved corneal shape.

Trust comment: Prospective randomized controlled clinical trial with objective imaging outcomes and decent sample size (eyes and fellow-eye controls).

Study Details

PMID:22322165
Participants:73
Impact:decrease of -0.21 μm (2.80 → 2.59 μm; -7.5%; P = .01)
Trust score:4/5

spherical refraction

1 evidences

Adding transepithelial corneal collagen cross-linking to intracorneal ring surgery improved vision and reduced spherical refractive error more than ring surgery alone.

Trust comment: Randomized study but small sample (29 patients, 40 eyes) with short-term follow-up reported; methods acceptable but limited power.

Study Details

PMID:26356750
Participants:29
Impact:greater reduction with TE-CXL (statistically significant at 3 and 6 months)
Trust score:3/5

topographic/refractive progression

1 evidences

Adding transepithelial corneal collagen cross-linking to intracorneal ring surgery improved vision and reduced spherical refractive error more than ring surgery alone.

Trust comment: Randomized study but small sample (29 patients, 40 eyes) with short-term follow-up reported; methods acceptable but limited power.

Study Details

PMID:26356750
Participants:29
Impact:reduced progression with addition of TE-CXL
Trust score:3/5

procollagen Type 1 N-terminal propeptide

1 evidences

An exercise program (10,000 steps plus jumps) decreased bone resorption markers and increased bone mineral density over 6 months in premenopausal women.

Trust comment: Randomized controlled trial with objective biochemical and BMD endpoints and reasonable completion rate, though moderate sample size.

Study Details

PMID:37917954
Participants:42
Impact:-6.74 μg/L (difference at 3 months, p=0.023)
Trust score:4/5

C-terminal telopeptide of Type I collagen

1 evidences

An exercise program (10,000 steps plus jumps) decreased bone resorption markers and increased bone mineral density over 6 months in premenopausal women.

Trust comment: Randomized controlled trial with objective biochemical and BMD endpoints and reasonable completion rate, though moderate sample size.

Study Details

PMID:37917954
Participants:42
Impact:-83 ng/L (difference at 3 months, p=0.043)
Trust score:4/5

bone mineral density (femoral neck / total hip / lumbar spine)

1 evidences

An exercise program (10,000 steps plus jumps) decreased bone resorption markers and increased bone mineral density over 6 months in premenopausal women.

Trust comment: Randomized controlled trial with objective biochemical and BMD endpoints and reasonable completion rate, though moderate sample size.

Study Details

PMID:37917954
Participants:42
Impact:+0.024 / +0.036 / +0.026 g/cm² at 6 months (p=0.016, p=0.004, p=0.020)
Trust score:4/5

pain (postoperative)

1 evidences

Using cold (4°C) riboflavin during corneal cross-linking significantly reduced early postoperative pain and related symptoms versus room-temperature riboflavin.

Trust comment: Prospective randomized clinical trial with adequate sample size and registered protocol; outcomes are patient-reported but differences are consistent and significant.

Study Details

PMID:33264161
Participants:98
Impact:−4.28 points at 2 hours (3.80 vs 8.08); sustained lower pain on days 1,2,4 (all p<0.05)
Trust score:4/5

tearing (postoperative)

1 evidences

Using cold (4°C) riboflavin during corneal cross-linking significantly reduced early postoperative pain and related symptoms versus room-temperature riboflavin.

Trust comment: Prospective randomized clinical trial with adequate sample size and registered protocol; outcomes are patient-reported but differences are consistent and significant.

Study Details

PMID:33264161
Participants:98
Impact:3.56 points lower at 2 hours (1.56 vs 8.29, p<0.05)
Trust score:4/5

photophobia (postoperative)

1 evidences

Using cold (4°C) riboflavin during corneal cross-linking significantly reduced early postoperative pain and related symptoms versus room-temperature riboflavin.

Trust comment: Prospective randomized clinical trial with adequate sample size and registered protocol; outcomes are patient-reported but differences are consistent and significant.

Study Details

PMID:33264161
Participants:98
Impact:−2.39 points at 2 hours (5.44 vs 7.83, p<0.05)
Trust score:4/5

sub-epithelial corneal nerve fiber density

1 evidences

A topical ω-3 fatty acid microemulsion after epi-off corneal cross-linking sped nerve fiber regeneration and improved symptoms faster than hyaluronic acid alone.

Trust comment: Prospective randomized study with objective confocal microscopy outcomes and clear statistical differences, but modest sample size.

Study Details

PMID:31571089
Participants:40
Impact:Group A 6.0 vs Group B 1.0 at 3 months (difference ≈+5.0, p=0.0001)
Trust score:4/5

ocular surface disease index (OSDI)

1 evidences

A topical ω-3 fatty acid microemulsion after epi-off corneal cross-linking sped nerve fiber regeneration and improved symptoms faster than hyaluronic acid alone.

Trust comment: Prospective randomized study with objective confocal microscopy outcomes and clear statistical differences, but modest sample size.

Study Details

PMID:31571089
Participants:40
Impact:OSDI 13 vs 28 at 3 months (≈−15 points in treatment vs control)
Trust score:4/5

nerve reflectivity/tortuosity

1 evidences

A topical ω-3 fatty acid microemulsion after epi-off corneal cross-linking sped nerve fiber regeneration and improved symptoms faster than hyaluronic acid alone.

Trust comment: Prospective randomized study with objective confocal microscopy outcomes and clear statistical differences, but modest sample size.

Study Details

PMID:31571089
Participants:40
Impact:no significant difference
Trust score:4/5

maximum simulated keratometry (Kmax)

1 evidences

Corneal collagen cross-linking halted progression of keratoconus over 3 years, flattening Kmax and improving visual acuity compared with controls.

Trust comment: Large randomized controlled trial with 3-year follow-up and objective clinical endpoints, providing robust evidence of efficacy.

Study Details

PMID:24393351
Participants:94
Impact:flattened by −0.72 to −1.03 D in treated eyes (−1.03±0.19 D at 36 months, p<0.001)
Trust score:5/5

uncorrected visual acuity (UCVA)

1 evidences

Corneal collagen cross-linking halted progression of keratoconus over 3 years, flattening Kmax and improving visual acuity compared with controls.

Trust comment: Large randomized controlled trial with 3-year follow-up and objective clinical endpoints, providing robust evidence of efficacy.

Study Details

PMID:24393351
Participants:94
Impact:improved by −0.15 logMAR at 36 months (p=0.009)
Trust score:5/5

mean recession reduction (mm)

1 evidences

Both techniques with acellular dermal matrix improved root coverage; coronally positioned flap gave higher mean coverage than the tunnel technique at 4 months.

Trust comment: Randomized, masked clinical trial but small sample (n=24) and short (4-month) follow-up limits generalizability.

Study Details

PMID:18533779
Participants:24
Impact:tunnel technique: mean gain 2.4 mm (78% coverage)
Trust score:3/5

continence improvement (Stamey grade and pad weight)

1 evidences

Durasphere and bovine collagen produced equivalent improvements in continence at 12 months, with Durasphere requiring less injected volume.

Trust comment: Large multicenter randomized double-blind trial with objective endpoints, supporting reliable results.

Study Details

PMID:11445471
Participants:355
Impact:no difference between Durasphere and bovine collagen at 12 months (equivalent efficacy)
Trust score:4/5

injected material volume

1 evidences

Durasphere and bovine collagen produced equivalent improvements in continence at 12 months, with Durasphere requiring less injected volume.

Trust comment: Large multicenter randomized double-blind trial with objective endpoints, supporting reliable results.

Study Details

PMID:11445471
Participants:355
Impact:Durasphere 4.83 mL vs bovine collagen 6.23 mL (P<0.001) — less material required with Durasphere
Trust score:4/5

corneal nerve parameters (CNFD, CNFL, CNBD, CTBD)

1 evidences

After corneal collagen crosslinking, high‑molecular‑weight hyaluronic acid eye drops accelerated nerve regeneration and faster recovery of corneal sensitivity compared with low‑molecular‑weight HA or no tears.

Trust comment: Randomized allocation with objective confocal microscopy and sensitivity measures, moderate sample (55 patients, 63 eyes); not double-blind and LMW formulation contained trehalose (limitation).

Study Details

PMID:40157723
Participants:55
Impact:faster recovery in HMW-HA group at 3–6 months (parameters returned to similar values by 12 months)
Trust score:4/5

corneal sensitivity

1 evidences

After corneal collagen crosslinking, high‑molecular‑weight hyaluronic acid eye drops accelerated nerve regeneration and faster recovery of corneal sensitivity compared with low‑molecular‑weight HA or no tears.

Trust comment: Randomized allocation with objective confocal microscopy and sensitivity measures, moderate sample (55 patients, 63 eyes); not double-blind and LMW formulation contained trehalose (limitation).

Study Details

PMID:40157723
Participants:55
Impact:HMW-HA returned to baseline by 3 months vs 6 months for LMW-HA and later for control
Trust score:4/5

dendritic cell (DC) density

1 evidences

After corneal collagen crosslinking, high‑molecular‑weight hyaluronic acid eye drops accelerated nerve regeneration and faster recovery of corneal sensitivity compared with low‑molecular‑weight HA or no tears.

Trust comment: Randomized allocation with objective confocal microscopy and sensitivity measures, moderate sample (55 patients, 63 eyes); not double-blind and LMW formulation contained trehalose (limitation).

Study Details

PMID:40157723
Participants:55
Impact:lower DC density in HMW-HA vs LMW-HA at 3 months (p=0.043); LMW-HA increased DC at 3 months (p=0.003)
Trust score:4/5

leukocyte infiltration

1 evidences

Topical high‑molecular‑weight hyaluronic acid after third molar extraction reduced local inflammatory cell infiltration and increased angiogenesis at 1 week, with no change in pain or oxidative stress markers at that time point.

Trust comment: Small controlled clinical study (n=40) showing local anti-inflammatory histologic effects but limited clinical/biochemical changes at 1 week and short follow-up.

Study Details

PMID:26027861
Participants:40
Impact:decreased in HA group at 1 week (statistically significant)
Trust score:3/5

pain (VAS) and oxidative stress (GSH, LPO)

1 evidences

Topical high‑molecular‑weight hyaluronic acid after third molar extraction reduced local inflammatory cell infiltration and increased angiogenesis at 1 week, with no change in pain or oxidative stress markers at that time point.

Trust comment: Small controlled clinical study (n=40) showing local anti-inflammatory histologic effects but limited clinical/biochemical changes at 1 week and short follow-up.

Study Details

PMID:26027861
Participants:40
Impact:no significant change at 1 week
Trust score:3/5

primary graft patency

1 evidences

Collagen-impregnated polyester grafts had slightly lower 2-year primary patency than saphenous vein, but differences were not statistically significant.

Trust comment: Prospective randomized clinical trial with 2-year follow-up and moderate sample size; borderline statistical significance limits strong conclusions.

Study Details

PMID:17448975
Participants:85
Impact:-14 percentage points (67% vs 81% at 2 years; P=0.065)
Trust score:4/5

secondary graft patency

1 evidences

Collagen-impregnated polyester grafts had slightly lower 2-year primary patency than saphenous vein, but differences were not statistically significant.

Trust comment: Prospective randomized clinical trial with 2-year follow-up and moderate sample size; borderline statistical significance limits strong conclusions.

Study Details

PMID:17448975
Participants:85
Impact:-4 percentage points (77% vs 81% at 2 years; P=0.298)
Trust score:4/5

predictors of occlusion

1 evidences

Collagen-impregnated polyester grafts had slightly lower 2-year primary patency than saphenous vein, but differences were not statistically significant.

Trust comment: Prospective randomized clinical trial with 2-year follow-up and moderate sample size; borderline statistical significance limits strong conclusions.

Study Details

PMID:17448975
Participants:85
Impact:no predictive factors identified
Trust score:4/5

apex thickness

1 evidences

After corneal collagen crosslinking the cornea thinned at 1 month then partially recovered; at 12 months apex and pupil-center thickness returned to baseline but the thinnest pachymetry remained slightly decreased.

Trust comment: Prospective randomized controlled trial with sham and fellow-eye controls and serial objective measurements.

Study Details

PMID:21420594
Participants:82
Impact:1 month -23.8 μm (mean); returned to baseline by 12 months (P=.11)
Trust score:5/5

thinnest pachymetry

1 evidences

After corneal collagen crosslinking the cornea thinned at 1 month then partially recovered; at 12 months apex and pupil-center thickness returned to baseline but the thinnest pachymetry remained slightly decreased.

Trust comment: Prospective randomized controlled trial with sham and fellow-eye controls and serial objective measurements.

Study Details

PMID:21420594
Participants:82
Impact:remained decreased -6.6 μm from baseline at 12 months (P=.01)
Trust score:5/5

pupil-center thickness

1 evidences

After corneal collagen crosslinking the cornea thinned at 1 month then partially recovered; at 12 months apex and pupil-center thickness returned to baseline but the thinnest pachymetry remained slightly decreased.

Trust comment: Prospective randomized controlled trial with sham and fellow-eye controls and serial objective measurements.

Study Details

PMID:21420594
Participants:82
Impact:transient thinning with recovery to baseline by 12 months (P=.06)
Trust score:5/5

incontinence cure rate (collagen injection)

1 evidences

Autologous myoblast/fibroblast injections cured most patients with stress urinary incontinence, whereas collagen injections cured only two patients.

Trust comment: Randomized human trial but small and imbalanced groups and limited reporting for the collagen arm reduce certainty.

Study Details

PMID:17701044
Participants:91
Impact:2 patients cured (~7% of collagen group, 2/28)
Trust score:3/5

incontinence cure rate (autologous cell injection)

1 evidences

Autologous myoblast/fibroblast injections cured most patients with stress urinary incontinence, whereas collagen injections cured only two patients.

Trust comment: Randomized human trial but small and imbalanced groups and limited reporting for the collagen arm reduce certainty.

Study Details

PMID:17701044
Participants:91
Impact:50 patients cured (39 women + 11 men out of 63; ~79%)
Trust score:3/5

urethral/rhabdosphincter thickness and contractility

1 evidences

Autologous myoblast/fibroblast injections cured most patients with stress urinary incontinence, whereas collagen injections cured only two patients.

Trust comment: Randomized human trial but small and imbalanced groups and limited reporting for the collagen arm reduce certainty.

Study Details

PMID:17701044
Participants:91
Impact:improved after autologous cell injection (thickness 2.103→3.303 mm; contractility 0.56→1.462 mm)
Trust score:3/5

minimum pachymetry

1 evidences

Corneal collagen crosslinking effectively reduced progression of keratoconus over 5 years, with treated eyes showing decreased keratometry compared to progression in control eyes.

Trust comment: Prospective randomized contralateral-eye controlled trial with objective outcomes and 5-year follow-up.

Study Details

PMID:34117699
Participants:38
Impact:treated -32.49 ± 26.32 μm vs control -13.57 ± 24.11 μm (p<0.01)
Trust score:5/5

corneal astigmatism

1 evidences

Corneal collagen crosslinking effectively reduced progression of keratoconus over 5 years, with treated eyes showing decreased keratometry compared to progression in control eyes.

Trust comment: Prospective randomized contralateral-eye controlled trial with objective outcomes and 5-year follow-up.

Study Details

PMID:34117699
Participants:38
Impact:treated -0.45 ± 1.31 D vs control +0.63 ± 1.52 D (p<0.01)
Trust score:5/5

night driving (subjective score)

1 evidences

Patients reported improvements in several subjective visual symptoms (night driving, reading, diplopia, glare, halo, starbursts, foreign-body sensation) one year after corneal collagen crosslinking.

Trust comment: Prospective randomized controlled trial using validated subjective symptom ratings that corroborate objective improvements.

Study Details

PMID:22342006
Participants:76
Impact:mean 3.2 → 2.8 (improvement)
Trust score:5/5

difficulty reading (subjective score)

1 evidences

Patients reported improvements in several subjective visual symptoms (night driving, reading, diplopia, glare, halo, starbursts, foreign-body sensation) one year after corneal collagen crosslinking.

Trust comment: Prospective randomized controlled trial using validated subjective symptom ratings that corroborate objective improvements.

Study Details

PMID:22342006
Participants:76
Impact:mean 3.1 → 2.9 (improvement)
Trust score:5/5

glare and halo (subjective scores)

1 evidences

Patients reported improvements in several subjective visual symptoms (night driving, reading, diplopia, glare, halo, starbursts, foreign-body sensation) one year after corneal collagen crosslinking.

Trust comment: Prospective randomized controlled trial using validated subjective symptom ratings that corroborate objective improvements.

Study Details

PMID:22342006
Participants:76
Impact:glare 3.1 → 2.7; halo 2.9 → 2.5 (improvements)
Trust score:5/5

type II fiber cross-sectional area

1 evidences

26 participants in a 10-week resistance training study; a multi-ingredient supplement (including calcium citrate) increased type II muscle fiber size more than collagen, with similar satellite cell content.

Trust comment: Controlled supplementation trial in humans with muscle biopsies but small sample (n=26) limiting precision; outcomes directly compare collagen supplement to another protein mix.

Study Details

PMID:39475860
Participants:26
Impact:MIS produced greater increase in type II fCSA vs Collagen control (ES = 0.89)
Trust score:3/5

myonuclear accretion (myonuclei per fiber)

1 evidences

26 participants in a 10-week resistance training study; a multi-ingredient supplement (including calcium citrate) increased type II muscle fiber size more than collagen, with similar satellite cell content.

Trust comment: Controlled supplementation trial in humans with muscle biopsies but small sample (n=26) limiting precision; outcomes directly compare collagen supplement to another protein mix.

Study Details

PMID:39475860
Participants:26
Impact:no between-group difference; change correlated with hypertrophy in Collagen group only
Trust score:3/5

satellite cell activation/content

1 evidences

26 participants in a 10-week resistance training study; a multi-ingredient supplement (including calcium citrate) increased type II muscle fiber size more than collagen, with similar satellite cell content.

Trust comment: Controlled supplementation trial in humans with muscle biopsies but small sample (n=26) limiting precision; outcomes directly compare collagen supplement to another protein mix.

Study Details

PMID:39475860
Participants:26
Impact:SC content similar; trend toward greater SC activation with MIS after training/damage (ES = 0.70)
Trust score:3/5

Reconstructive failure

1 evidences

Randomized trial comparing two acellular dermal matrices (both collagen-containing) found no difference in overall reconstructive failure or patient-reported outcomes; AlloDerm associated with higher seroma odds.

Trust comment: Large randomized controlled trial (n=302) with prespecified outcomes and multivariable analysis, high internal validity.

Study Details

PMID:38085977
Participants:302
Impact:no significant difference (AlloDerm 9.3% vs Cortiva 8.3%)
Trust score:5/5

Seroma formation

2 evidences

Insertion of Gentacoll (collagen sponge with gentamicin) after mastectomy reduced infections, seromas, drainage volumes and hospital stay versus control.

Trust comment: Randomized prospective trial directly testing a collagen-based implant (Gentacoll) with clear clinical endpoints but modest sample size (n=44).

Study Details

PMID:20926017
Participants:44
Impact:reduced in Gentacoll group (statistically significant)
Trust score:3/5

Randomized trial comparing two acellular dermal matrices (both collagen-containing) found no difference in overall reconstructive failure or patient-reported outcomes; AlloDerm associated with higher seroma odds.

Trust comment: Large randomized controlled trial (n=302) with prespecified outcomes and multivariable analysis, high internal validity.

Study Details

PMID:38085977
Participants:302
Impact:higher with AlloDerm (12% vs 7.6%; OR 1.93, p=0.047)
Trust score:5/5

Patient-reported outcomes (BREAST-Q)

1 evidences

Randomized trial comparing two acellular dermal matrices (both collagen-containing) found no difference in overall reconstructive failure or patient-reported outcomes; AlloDerm associated with higher seroma odds.

Trust comment: Large randomized controlled trial (n=302) with prespecified outcomes and multivariable analysis, high internal validity.

Study Details

PMID:38085977
Participants:302
Impact:no significant difference between ADMs
Trust score:5/5

Postoperative pulmonary fistula incidence

1 evidences

Randomized trial found a sheet-type absorbable topical collagen hemostat reduced postoperative pulmonary fistula incidence compared with a combined fibrin-glue-based approach.

Trust comment: Randomized controlled trial with clear outcome reporting and significant result, though single-center and modest sample size.

Study Details

PMID:20190704
Participants:72
Impact:reduced with collagen sheet (7.9% vs 17.6%; p=0.044)
Trust score:4/5

Feasibility / safety

1 evidences

Randomized trial found a sheet-type absorbable topical collagen hemostat reduced postoperative pulmonary fistula incidence compared with a combined fibrin-glue-based approach.

Trust comment: Randomized controlled trial with clear outcome reporting and significant result, though single-center and modest sample size.

Study Details

PMID:20190704
Participants:72
Impact:collagen hemostat feasible and safe (no blood-product exposure)
Trust score:4/5

symptom score

1 evidences

Dissolvable collagen punctal plugs in 62 patients with aqueous-deficient dry eye reduced symptoms and increased tear stability and volume within 12 days.

Trust comment: Randomized allocation to plug locations, clear objective measures, moderate sample size, but short follow-up (12 days).

Study Details

PMID:12535050
Participants:62
Impact:median 7 → 3 (−4 points)
Trust score:4/5

tear stability (tear thinning time)

1 evidences

Dissolvable collagen punctal plugs in 62 patients with aqueous-deficient dry eye reduced symptoms and increased tear stability and volume within 12 days.

Trust comment: Randomized allocation to plug locations, clear objective measures, moderate sample size, but short follow-up (12 days).

Study Details

PMID:12535050
Participants:62
Impact:median 3 s → 5 s by day 5
Trust score:4/5

tear volume (tear meniscus height)

1 evidences

Dissolvable collagen punctal plugs in 62 patients with aqueous-deficient dry eye reduced symptoms and increased tear stability and volume within 12 days.

Trust comment: Randomized allocation to plug locations, clear objective measures, moderate sample size, but short follow-up (12 days).

Study Details

PMID:12535050
Participants:62
Impact:median 0.13 mm → 0.20 mm by day 5
Trust score:4/5

serum calcium

2 evidences

A single teriparatide injection caused short-term changes in calcium metabolism and biphasic changes in bone turnover markers; vitamin D metabolites (1,25(OH)2D) rose transiently but Vitamin D was not the intervention.

Trust comment: Randomized, double-blind, placebo-controlled pharmacodynamic study with complete follow-up but small sample size limits precision.

Study Details

PMID:23093347
Participants:30
Impact:Transient increase peaking 4–6 h (max mean 9.58 mg/dL in 56.5 μg group), returning to baseline by 24 h
Trust score:4/5

Adding calcitriol to esomeprazole did not improve bone mineral density; only minor changes in calcium and bone markers were observed.

Trust comment: Large randomized study but treatment exposure was very short (~10 days), limiting ability to detect BMD changes.

Study Details

PMID:25046547
Participants:386
Impact:slightly higher in calcitriol group (small difference)
Trust score:3/5

C1M (type I collagen fragment)

1 evidences

Matched serum and tissue from UNIFI trial patients (n=97) show specific serum collagen fragments (C1M, Pro-Collagen 22, CTX-III, ELP-3) correlate with intestinal inflammatory-activated fibroblasts and change with ustekinumab response.

Trust comment: Robust matched tissue-serum multi-omic analysis from a randomized trial cohort (n=97) with clear correlations, though some conflicts of interest noted.

Study Details

PMID:39969502
Participants:97
Impact:positive correlation with IIAF (R=0.42, p=5.5×10⁻⁵); decreased post-ustekinumab (p≤0.05)
Trust score:4/5

Pro-Collagen 22

1 evidences

Matched serum and tissue from UNIFI trial patients (n=97) show specific serum collagen fragments (C1M, Pro-Collagen 22, CTX-III, ELP-3) correlate with intestinal inflammatory-activated fibroblasts and change with ustekinumab response.

Trust comment: Robust matched tissue-serum multi-omic analysis from a randomized trial cohort (n=97) with clear correlations, though some conflicts of interest noted.

Study Details

PMID:39969502
Participants:97
Impact:positive correlation with IIAF (R=0.37, p=0.00048); decreased post-ustekinumab (p≤0.05)
Trust score:4/5

CTX-III (type III collagen fragment)

1 evidences

Matched serum and tissue from UNIFI trial patients (n=97) show specific serum collagen fragments (C1M, Pro-Collagen 22, CTX-III, ELP-3) correlate with intestinal inflammatory-activated fibroblasts and change with ustekinumab response.

Trust comment: Robust matched tissue-serum multi-omic analysis from a randomized trial cohort (n=97) with clear correlations, though some conflicts of interest noted.

Study Details

PMID:39969502
Participants:97
Impact:negative correlation with IIAF (R=−0.28, p=0.0053); tended to increase toward healthy levels in responders
Trust score:4/5

collagen synthesis

2 evidences

Split-face trial in which hyaluronic acid fillers improved nasolabial/crow's-feet wrinkles and showed increased local collagen synthesis and good tolerability up to 180 days.

Trust comment: Prospective, randomized, split-face blinded study with objective measures and moderate sample size; assesses collagen stimulation but not collagen supplementation.

Study Details

PMID:28595250
Participants:61
Impact:significant increase at treated sites (no % reported)
Trust score:4/5

In 50 patients randomized to ACHA versus Restylane, the amino-acid cross-linked HA filler promoted dermal fibroblast activity, increased skin thickness and collagen generation and provided longer-lasting volume.

Trust comment: Randomized clinical component (n=50) with supportive in vitro and animal data; moderate sample size and industry translation but not a nutritional collagen intervention.

Study Details

PMID:37265096
Participants:50
Impact:increased collagen generation (reported increase in skin collagen)
Trust score:3/5

HA retention / residual volume

1 evidences

In 50 patients randomized to ACHA versus Restylane, the amino-acid cross-linked HA filler promoted dermal fibroblast activity, increased skin thickness and collagen generation and provided longer-lasting volume.

Trust comment: Randomized clinical component (n=50) with supportive in vitro and animal data; moderate sample size and industry translation but not a nutritional collagen intervention.

Study Details

PMID:37265096
Participants:50
Impact:greater residual volume at 12 months versus comparator
Trust score:3/5

wound infection rate

3 evidences

Randomized controlled trial (161 patients) found that adding a gentamicin-containing collagen sponge (Collatamp®) to pilonidal excision with primary suture did not significantly change wound infection rates, wound healing, or recurrence at 1 year.

Trust comment: Prospective randomized multicenter trial with concealed allocation and 161 patients, providing moderate-high quality evidence that topical gentamicin-collagen sponge did not improve clinical outcomes.

Study Details

PMID:20734046
Participants:161
Impact:no statistically significant difference between Collatamp® and control groups
Trust score:4/5

In children with partial-thickness burns, collagenase ointment and silver sulfadiazine produced similar clinical outcomes and need for grafting; collagenase had more wound infections (trend) and higher product cost.

Trust comment: Prospective randomized pediatric trial directly evaluating a collagenase product; moderate sample size and randomized design support reasonable trustworthiness.

Study Details

PMID:22703794
Participants:100
Impact:7 infections with collagenase vs 1 with SSD (P=0.06)
Trust score:4/5

Implanting a gentamycin-containing collagen sponge under the wound did not reduce wound infection after ileostomy closure compared with an identical collagen sponge without antibiotic.

Trust comment: Well-designed double-blind RCT with adequate sample (n=80) and clear negative result.

Study Details

PMID:16228839
Participants:80
Impact:no difference (10% overall; gentamycin 4/40 vs collagen-only 4/40; p=1.0)
Trust score:4/5

wound healing (3 months and 1 year)

1 evidences

Randomized controlled trial (161 patients) found that adding a gentamicin-containing collagen sponge (Collatamp®) to pilonidal excision with primary suture did not significantly change wound infection rates, wound healing, or recurrence at 1 year.

Trust comment: Prospective randomized multicenter trial with concealed allocation and 161 patients, providing moderate-high quality evidence that topical gentamicin-collagen sponge did not improve clinical outcomes.

Study Details

PMID:20734046
Participants:161
Impact:no significant difference at 1 year; small non-significant increase in healed wounds at 3 months (77% vs 66%, p=0.138)
Trust score:4/5

recurrence/reoperation rate

1 evidences

Randomized controlled trial (161 patients) found that adding a gentamicin-containing collagen sponge (Collatamp®) to pilonidal excision with primary suture did not significantly change wound infection rates, wound healing, or recurrence at 1 year.

Trust comment: Prospective randomized multicenter trial with concealed allocation and 161 patients, providing moderate-high quality evidence that topical gentamicin-collagen sponge did not improve clinical outcomes.

Study Details

PMID:20734046
Participants:161
Impact:no significant reduction in recurrence; slightly more reoperations in Collatamp® group (10% vs 4%, p=0.213)
Trust score:4/5

horizontal/vertical alveolar bone dimensional change

1 evidences

Sealing extraction sockets with a porcine collagen matrix gave similar 1-year implant and bone outcomes as connective tissue graft, avoiding a donor site.

Trust comment: Randomized controlled trial on humans with objective CBCT/radiographic measures and complete follow-up, moderate-high quality.

Study Details

PMID:25738178
Participants:30
Impact:between-group differences 0.05–0.13 mm (NS)
Trust score:4/5

peri-implant marginal bone level change

1 evidences

Sealing extraction sockets with a porcine collagen matrix gave similar 1-year implant and bone outcomes as connective tissue graft, avoiding a donor site.

Trust comment: Randomized controlled trial on humans with objective CBCT/radiographic measures and complete follow-up, moderate-high quality.

Study Details

PMID:25738178
Participants:30
Impact:difference 0.07 ± 0.11 mm (P=0.41, NS)
Trust score:4/5

probing depth reduction

2 evidences

Adding autogenous bone (with or without bioactive glass) to a collagen membrane led to greater periodontal defect healing than collagen membrane alone.

Trust comment: Randomized treatment of 32 defects in 22 subjects; small sample but randomized and clinically relevant outcomes.

Study Details

PMID:22167034
Participants:22
Impact:Significant reduction in all groups with greater improvement in test groups (CM + autogenous bone or + bone mixed with bioactive glass)
Trust score:3/5

In periodontal intraosseous defects, adding a collagen membrane to enamel matrix protein therapy did not improve clinical or radiographic outcomes compared with either therapy alone.

Trust comment: Moderate-sized clinical comparative study directly testing a collagen membrane; randomized status unclear and sample modest, but outcomes are clinical and relevant.

Study Details

PMID:12516831
Participants:61
Impact:No significant difference between combined therapy and either monotherapy at 6 months and 1 year
Trust score:3/5

hyperinflammation (cytokines/CRP)

1 evidences

In people recovering from COVID-19, intramuscular polymerised type I collagen reduced inflammatory markers and sped systemic recovery of physiological networks, with stronger effects in women.

Trust comment: Double-blind randomized trial with objective biomarker measures but small completed sample (n=37) for the network analysis.

Study Details

PMID:37899681
Participants:37
Impact:decrease (significant; IP-10, IL-8, IL-1Ra, CRP and others reduced on days 1–90; p<0.05–0.01)
Trust score:4/5

physiological network correlation (recovery speed)

1 evidences

In people recovering from COVID-19, intramuscular polymerised type I collagen reduced inflammatory markers and sped systemic recovery of physiological networks, with stronger effects in women.

Trust comment: Double-blind randomized trial with objective biomarker measures but small completed sample (n=37) for the network analysis.

Study Details

PMID:37899681
Participants:37
Impact:decrease in baseline→post-treatment network correlation (faster recovery; female PTIC baseline→day1 rho=0.17 vs male PTIC rho=0.36)
Trust score:4/5

maximal keratometric power (Kmax)

1 evidences

Corneal cross-linking (riboflavin+UVA) slowed progression of keratoconus (flattened Kmax) but caused more transient corneal haze and epithelial erosions.

Trust comment: Randomized double-blind placebo-controlled design but small, underpowered sample (terminated early; n=29) limits precision.

Study Details

PMID:26194634
Participants:29
Impact:decrease −0.35 ±0.58 D/year in treatment vs increase +0.11 ±0.61 D/year in control (difference p=0.02)
Trust score:3/5

corneal haze

1 evidences

Corneal cross-linking (riboflavin+UVA) slowed progression of keratoconus (flattened Kmax) but caused more transient corneal haze and epithelial erosions.

Trust comment: Randomized double-blind placebo-controlled design but small, underpowered sample (terminated early; n=29) limits precision.

Study Details

PMID:26194634
Participants:29
Impact:increased (significantly more haze in treatment group; p<0.001)
Trust score:3/5

buccal contour change (ridge preservation)

1 evidences

After tooth extraction, placement of deproteinized bovine bone mineral (with or without adjuncts) reduced buccal contour loss compared with no treatment, but overall differences among tested modalities were not statistically significant.

Trust comment: Randomized clinical trial but small sample (35 sites) and limited power to detect differences across four arms.

Study Details

PMID:29889920
Participants:35
Impact:less contour loss with grafts (~−0.87 to −1.26 mm) vs no treatment (~−2.15 mm); DBBM reduced contour change roughly by ~1 mm compared to no treatment
Trust score:3/5

implant placement feasibility / secondary outcomes

1 evidences

After tooth extraction, placement of deproteinized bovine bone mineral (with or without adjuncts) reduced buccal contour loss compared with no treatment, but overall differences among tested modalities were not statistically significant.

Trust comment: Randomized clinical trial but small sample (35 sites) and limited power to detect differences across four arms.

Study Details

PMID:29889920
Participants:35
Impact:no significant differences among groups for primary/secondary outcomes (p>0.05)
Trust score:3/5

alveolar bone level (ABL)

1 evidences

Using a resorbable collagen membrane with primary closure after lower third molar extraction improved distal alveolar bone level of the adjacent second molar and improved periodontal measures compared with secondary closure.

Trust comment: Randomized controlled study with 84 completers and objective radiographic and clinical endpoints; moderate follow-up (3 months).

Study Details

PMID:36966313
Participants:84
Impact:increase with membrane-based primary closure: mean T2−T1 +1.36 mm (MBPC) vs +0.72 mm (PC) and −0.38 mm (SC); MBPC superior (p=0.000)
Trust score:4/5

periodontal pocket depth (PPD)

1 evidences

Using a resorbable collagen membrane with primary closure after lower third molar extraction improved distal alveolar bone level of the adjacent second molar and improved periodontal measures compared with secondary closure.

Trust comment: Randomized controlled study with 84 completers and objective radiographic and clinical endpoints; moderate follow-up (3 months).

Study Details

PMID:36966313
Participants:84
Impact:decreased across groups (DB and DL pockets significantly reduced; p<0.05)
Trust score:4/5

urinary NTx (collagen crosslink marker)

1 evidences

Ancillary analysis measuring preoperative vitamin D showed vitamin D levels had low predictive accuracy for mid-urethral sling surgical success; urinary NTx was a better predictor.

Trust comment: Ancillary analysis with a moderate biomarker sample (n=150) and objective ROC comparison, but observational ancillary design limits causal inference.

Study Details

PMID:27113967
Participants:116
Impact:predictive AUC=0.702 (significantly higher than Valsalva LPP and MUCP; p=0.02–0.03)
Trust score:3/5

root coverage (CEJ–GM)

1 evidences

In multiple adjacent gingival recessions, xenogenic collagen matrix reduced surgical time and sped patient recovery but provided less root coverage and keratinized tissue gain than autologous connective tissue graft.

Trust comment: Large multicentre randomized assessor-blinded trial with low loss to follow-up and clustered multilevel analysis, high quality evidence.

Study Details

PMID:29087001
Participants:187
Impact:CTG mean change +2.1 mm vs CMX +1.7 mm (difference 0.44 mm; 95% CI 0.25–0.63)
Trust score:5/5

complete root coverage

1 evidences

In multiple adjacent gingival recessions, xenogenic collagen matrix reduced surgical time and sped patient recovery but provided less root coverage and keratinized tissue gain than autologous connective tissue graft.

Trust comment: Large multicentre randomized assessor-blinded trial with low loss to follow-up and clustered multilevel analysis, high quality evidence.

Study Details

PMID:29087001
Participants:187
Impact:CTG 70% vs CMX 48% (OR 4.02; 95% CI 1.83–8.83)
Trust score:5/5

time to recovery (OHIP)

1 evidences

In multiple adjacent gingival recessions, xenogenic collagen matrix reduced surgical time and sped patient recovery but provided less root coverage and keratinized tissue gain than autologous connective tissue graft.

Trust comment: Large multicentre randomized assessor-blinded trial with low loss to follow-up and clustered multilevel analysis, high quality evidence.

Study Details

PMID:29087001
Participants:187
Impact:CMX faster: 4.2 days vs CTG 6.0 days (difference −1.8 days); less perceived hardship and shorter surgical time (CTG 69.7 vs CMX 53.2 min)
Trust score:5/5

facial bone thickness reduction

1 evidences

Randomized trial of 60 implants comparing synthetic PLA vs collagen membranes with biphasic calcium phosphate graft: similar facial bone thickness loss at 6 months and all implants osseointegrated.

Trust comment: Randomized controlled clinical trial with objective CBCT measures; moderate sample (60 implants) though patient count not explicitly reported.

Study Details

PMID:29028848
Participants:60
Impact:control (collagen) reductions: 34.80% (platform), 24.06% (2 mm), 19.52% (4 mm), 20.45% (6 mm); no significant difference vs synthetic (P>0.05)
Trust score:4/5

elastase activity

1 evidences

Treatment of venous leg ulcers with an ORC/collagen matrix significantly reduced protease activities in wound exudate compared with standard care over 12 weeks.

Trust comment: Human clinical comparison with clear biochemical outcomes but small sample size (n=27) limiting power.

Study Details

PMID:18494625
Participants:27
Impact:decreased (significant vs control)
Trust score:3/5

plasmin activity

1 evidences

Treatment of venous leg ulcers with an ORC/collagen matrix significantly reduced protease activities in wound exudate compared with standard care over 12 weeks.

Trust comment: Human clinical comparison with clear biochemical outcomes but small sample size (n=27) limiting power.

Study Details

PMID:18494625
Participants:27
Impact:decreased (significant vs control)
Trust score:3/5

gelatinase activity

1 evidences

Treatment of venous leg ulcers with an ORC/collagen matrix significantly reduced protease activities in wound exudate compared with standard care over 12 weeks.

Trust comment: Human clinical comparison with clear biochemical outcomes but small sample size (n=27) limiting power.

Study Details

PMID:18494625
Participants:27
Impact:decreased (significant vs control)
Trust score:3/5

MMP-2 concentration

1 evidences

Treatment of venous leg ulcers with an ORC/collagen matrix significantly reduced protease activities in wound exudate compared with standard care over 12 weeks.

Trust comment: Human clinical comparison with clear biochemical outcomes but small sample size (n=27) limiting power.

Study Details

PMID:18494625
Participants:27
Impact:no significant change
Trust score:3/5

lower-leg growth rate

1 evidences

In 27 children, halving inhaled steroid dose and adding formoterol sped short-term leg growth and increased collagen turnover markers without worsening asthma control.

Trust comment: Randomized double-blind crossover RCT in children with objective collagen marker and growth endpoints, but small sample size.

Study Details

PMID:10999872
Participants:27
Impact:+0.14 mm/week (increase during formoterol + lower-dose budesonide vs higher-dose budesonide; p=0.02)
Trust score:4/5

coronal ridge width reduction

1 evidences

Randomized trial (n=28) comparing collagen matrix seal vs collagen sponge with bone allograft for alveolar ridge preservation found both materials minimized ridge resorption with no significant differences.

Trust comment: Randomized controlled clinical trial with complete follow-up (n=28); modest sample size but direct clinical outcomes for collagen-based materials.

Study Details

PMID:28303642
Participants:28
Impact:CMS 1.21 mm (−14.91%) vs CS 1.47 mm (−20.40%) at 4 months
Trust score:4/5

vertical buccal bone resorption

1 evidences

Randomized trial (n=28) comparing collagen matrix seal vs collagen sponge with bone allograft for alveolar ridge preservation found both materials minimized ridge resorption with no significant differences.

Trust comment: Randomized controlled clinical trial with complete follow-up (n=28); modest sample size but direct clinical outcomes for collagen-based materials.

Study Details

PMID:28303642
Participants:28
Impact:CMS 0.30 mm vs CS 0.79 mm (4 months)
Trust score:4/5

buccal gingival thickness (coronal)

1 evidences

Randomized trial (n=28) comparing collagen matrix seal vs collagen sponge with bone allograft for alveolar ridge preservation found both materials minimized ridge resorption with no significant differences.

Trust comment: Randomized controlled clinical trial with complete follow-up (n=28); modest sample size but direct clinical outcomes for collagen-based materials.

Study Details

PMID:28303642
Participants:28
Impact:increase: CMS +0.9 mm vs CS +0.5 mm
Trust score:4/5

lumbar spine standardized BMD

1 evidences

Women who previously received zoledronate had higher BMD and persistently lower bone turnover markers over 5 years compared with controls.

Trust comment: Subgroup follow-up of a randomized trial with objective BMD and bone-turnover measures over 5 years; good quality though observational relative to original randomization.

Study Details

PMID:38630878
Participants:224
Impact:1123 vs 985 mg/cm2 (zoledronate vs control) at sub-study entry (P<0.0001)
Trust score:4/5

urinary C-telopeptide of type I collagen

1 evidences

Women who previously received zoledronate had higher BMD and persistently lower bone turnover markers over 5 years compared with controls.

Trust comment: Subgroup follow-up of a randomized trial with objective BMD and bone-turnover measures over 5 years; good quality though observational relative to original randomization.

Study Details

PMID:38630878
Participants:224
Impact:significantly lower in zoledronate arm throughout follow-up (P<0.00001)
Trust score:4/5

serum PINP (pro-collagen I N-propeptide)

1 evidences

Women who previously received zoledronate had higher BMD and persistently lower bone turnover markers over 5 years compared with controls.

Trust comment: Subgroup follow-up of a randomized trial with objective BMD and bone-turnover measures over 5 years; good quality though observational relative to original randomization.

Study Details

PMID:38630878
Participants:224
Impact:significantly lower in zoledronate arm throughout follow-up (P<0.00001)
Trust score:4/5

anterior vaginal wall prolapse recurrence (point Ba > -1)

1 evidences

Use of a porcine collagen (Pelvicol) implant at anterior repair reduced anatomical anterior prolapse recurrence at 1 year compared with repair alone.

Trust comment: Multicenter randomized trial with 201 analyzed and 1-year follow-up; clinically relevant endpoints and reasonable quality.

Study Details

PMID:17162041
Participants:201
Impact:7% with implant vs 19% without implant (absolute -12 percentage points; p=0.019)
Trust score:4/5

posterior recurrence

1 evidences

Use of a porcine collagen (Pelvicol) implant at anterior repair reduced anatomical anterior prolapse recurrence at 1 year compared with repair alone.

Trust comment: Multicenter randomized trial with 201 analyzed and 1-year follow-up; clinically relevant endpoints and reasonable quality.

Study Details

PMID:17162041
Participants:201
Impact:3% with implant vs 8% without implant (reported counts 3 vs 8 patients)
Trust score:4/5

osteocalcin (serum)

1 evidences

All cemented prosthesis designs led to early proximal femoral bone loss and transient increases in bone turnover markers; patterns were similar across designs.

Trust comment: Randomized clinical trial with 2-year follow-up and objective DXA and biochemical markers, supporting reliable within-study findings.

Study Details

PMID:23283370
Participants:120
Impact:Transient increase over first year (marker of osteoblast activity)
Trust score:4/5

lumbar spine areal BMD

1 evidences

Oral risedronate increased lumbar spine BMD and reduced clinical fractures in children with osteogenesis imperfecta at 1 year.

Trust comment: Multicenter randomized double-blind placebo-controlled trial with clear primary endpoint and adequate sample size; high quality.

Study Details

PMID:23927913
Participants:143
Impact:risedronate +16.3% vs placebo +7.6% at 1 year (difference +8.7%, p<0.0001)
Trust score:5/5

clinical fractures (1 year)

1 evidences

Oral risedronate increased lumbar spine BMD and reduced clinical fractures in children with osteogenesis imperfecta at 1 year.

Trust comment: Multicenter randomized double-blind placebo-controlled trial with clear primary endpoint and adequate sample size; high quality.

Study Details

PMID:23927913
Participants:143
Impact:29/94 (31%) risedronate vs 24/49 (49%) placebo (p=0.0446) — fewer fractures with risedronate
Trust score:5/5

corneal reepithelialization (complete healing at day 2)

1 evidences

RGTA eye drops after epi-off CXL sped corneal epithelial healing and reduced ocular symptoms faster than control.

Trust comment: Randomized clinical trial with clear participant count and statistically significant symptom and healing outcomes, though single-center and eye-based outcomes limit generalizability.

Study Details

PMID:28264130
Participants:60
Impact:83.3% (25/30) vs 13.3% (4/30) complete healing with RGTA vs control at day 2
Trust score:4/5

ocular pain

1 evidences

RGTA eye drops after epi-off CXL sped corneal epithelial healing and reduced ocular symptoms faster than control.

Trust comment: Randomized clinical trial with clear participant count and statistically significant symptom and healing outcomes, though single-center and eye-based outcomes limit generalizability.

Study Details

PMID:28264130
Participants:60
Impact:reduced (lower pain scores in RGTA group on days 0–2; P < .05)
Trust score:4/5

photophobia and other ocular symptoms

1 evidences

RGTA eye drops after epi-off CXL sped corneal epithelial healing and reduced ocular symptoms faster than control.

Trust comment: Randomized clinical trial with clear participant count and statistically significant symptom and healing outcomes, though single-center and eye-based outcomes limit generalizability.

Study Details

PMID:28264130
Participants:60
Impact:reduced (burning, stinging, tearing, photophobia lower on specified days; P < .05)
Trust score:4/5

nasal tip contour (esthetic outcome, Manchester Scar Scale)

1 evidences

Adding a collagen–elastin dermal matrix (Matriderm) to skin grafts improved nasal-tip contour versus full-thickness grafts, but two fistulae occurred in the Matriderm group.

Trust comment: Small retrospective comparative study (n=30) with blinded external evaluation, relevant to topical/implant collagen products but limited by size and retrospective design.

Study Details

PMID:21184067
Participants:30
Impact:marked improvement with combined epidermal/dermal replacement (Matriderm) vs conventional grafts (qualitative improvement)
Trust score:3/5

complications (fistula formation)

1 evidences

Adding a collagen–elastin dermal matrix (Matriderm) to skin grafts improved nasal-tip contour versus full-thickness grafts, but two fistulae occurred in the Matriderm group.

Trust comment: Small retrospective comparative study (n=30) with blinded external evaluation, relevant to topical/implant collagen products but limited by size and retrospective design.

Study Details

PMID:21184067
Participants:30
Impact:2 patients developed fistulae after Matriderm-aided transplantation
Trust score:3/5

Vaginal laxity (VLQ)

1 evidences

Two non‑surgical treatments (fractional radiofrequency and microneedling) improved vulvar appearance and symptoms and increased markers of collagen remodeling.

Trust comment: Randomized pilot clinical trial with histological endpoints and blinded photo assessment but small sample and short follow-up.

Study Details

PMID:36183506
Participants:30
Impact:≥ +1 ordinal level (subjective improvement by at least one VLQ level at 60 days)
Trust score:4/5

EQ-5D quality-of-life score

1 evidences

Two non‑surgical treatments (fractional radiofrequency and microneedling) improved vulvar appearance and symptoms and increased markers of collagen remodeling.

Trust comment: Randomized pilot clinical trial with histological endpoints and blinded photo assessment but small sample and short follow-up.

Study Details

PMID:36183506
Participants:30
Impact:+2.2 points (20.8 → 23.0) in FRF group at 60 days, p=0.001
Trust score:4/5

Type III collagen expression (histology)

1 evidences

Two non‑surgical treatments (fractional radiofrequency and microneedling) improved vulvar appearance and symptoms and increased markers of collagen remodeling.

Trust comment: Randomized pilot clinical trial with histological endpoints and blinded photo assessment but small sample and short follow-up.

Study Details

PMID:36183506
Participants:30
Impact:Increased (statistically significant, p<0.05)
Trust score:4/5

Manifest spherical equivalent refraction

1 evidences

Two corneal cross-linking procedures stabilized keratoconus over 12 months with modest differences; iontophoresis transepithelial treatment gave significant visual gains but slightly less corneal flattening than standard protocol.

Trust comment: Prospective randomized controlled trial with 12‑month follow-up but modest sample size (34 eyes, 25 patients).

Study Details

PMID:28283279
Participants:25
Impact:Change: +0.71 ±1.44 D (T‑ionto, P=0.03) vs +0.21 ±0.76 D (standard, P=0.38)
Trust score:4/5

Crestal bone loss (radiographic)

1 evidences

Immediate implants with platform switching and grafting (including bovine bone + collagen) showed less early crestal bone loss than controls.

Trust comment: Preliminary randomized study with very small sample (22 patients) and short follow-up; radiographic outcomes reported by independent observer.

Study Details

PMID:19548410
Participants:22
Impact:Mean loss: 0.30 mm (test) vs 1.19 mm (control); difference ≈ −0.89 mm, P ≤ 0.005
Trust score:3/5

Pocket probing depth / bleeding on probing / plaque index

1 evidences

Immediate implants with platform switching and grafting (including bovine bone + collagen) showed less early crestal bone loss than controls.

Trust comment: Preliminary randomized study with very small sample (22 patients) and short follow-up; radiographic outcomes reported by independent observer.

Study Details

PMID:19548410
Participants:22
Impact:No significant differences between groups
Trust score:3/5

Wound volume reduction (day 14)

1 evidences

In high‑risk vascular foot wounds, topical negative pressure showed greater reduction in wound depth at 14 days but no significant difference in wound volume or hydroxyproline (collagen surrogate).

Trust comment: Pilot randomized study with high dropout (48 recruited, 22 completed) and limited power; objective wound measures used.

Study Details

PMID:28583732
Participants:22
Impact:44.2% (TNP) vs 20.9% (control), P=0.15 (not significant)
Trust score:3/5

Maximum wound depth reduction (day 14)

1 evidences

In high‑risk vascular foot wounds, topical negative pressure showed greater reduction in wound depth at 14 days but no significant difference in wound volume or hydroxyproline (collagen surrogate).

Trust comment: Pilot randomized study with high dropout (48 recruited, 22 completed) and limited power; objective wound measures used.

Study Details

PMID:28583732
Participants:22
Impact:36.0% (TNP) vs 17.6% (control), P=0.03 (significant)
Trust score:3/5

Hydroxyproline level (collagen surrogate)

1 evidences

In high‑risk vascular foot wounds, topical negative pressure showed greater reduction in wound depth at 14 days but no significant difference in wound volume or hydroxyproline (collagen surrogate).

Trust comment: Pilot randomized study with high dropout (48 recruited, 22 completed) and limited power; objective wound measures used.

Study Details

PMID:28583732
Participants:22
Impact:58.0% (TNP) vs 94.5% (control), P=0.32 (not significant)
Trust score:3/5

Organ-space SSI without anastomotic leakage

1 evidences

Implantation of a gentamicin‑collagen product into the pelvic cavity reduced organ‑space surgical site infection when anastomotic leakage did not occur.

Trust comment: Large randomized trial (171 analyzed) powered for oncologic endpoints; infection outcomes secondary but reported with clear subgroup significance.

Study Details

PMID:24993838
Participants:171
Impact:2.6% (GCI) vs 13.8% (control), P=0.018 (reduced risk)
Trust score:4/5

Total surgical site infection (SSI)

1 evidences

Implantation of a gentamicin‑collagen product into the pelvic cavity reduced organ‑space surgical site infection when anastomotic leakage did not occur.

Trust comment: Large randomized trial (171 analyzed) powered for oncologic endpoints; infection outcomes secondary but reported with clear subgroup significance.

Study Details

PMID:24993838
Participants:171
Impact:18.6% (GCI) vs 25.9% (control), P=0.275 (not significant)
Trust score:4/5

doxycycline concentration in gingival crevicular fluid

1 evidences

In periodontitis patients, EDTA root etching increased doxycycline availability from a biodegradable collagen membrane compared with membrane alone.

Trust comment: Randomized clinical trial with direct measurement of drug release from a collagen membrane but small sample size limits generalizability.

Study Details

PMID:22181689
Participants:30
Impact:DOX-COL + EDTA retained more DOX at days 3–21; day 21 level 5.3 μg/mL vs no detectable DOX in DOX-COL group
Trust score:3/5

drug release retention (DOX)

1 evidences

In periodontitis patients, EDTA root etching increased doxycycline availability from a biodegradable collagen membrane compared with membrane alone.

Trust comment: Randomized clinical trial with direct measurement of drug release from a collagen membrane but small sample size limits generalizability.

Study Details

PMID:22181689
Participants:30
Impact:EDTA etching enhanced DOX availability and retention from the collagen membrane
Trust score:3/5

net left ventricular (LV) twist

1 evidences

In hypertensive patients with heart failure, higher circulating collagen turnover markers were associated with lower left ventricular twist, suggesting loss of myocardial collagen scaffolding is linked to impaired deformation.

Trust comment: Well-defined observational human study with objective imaging and biomarker data but observational design limits causal inference.

Study Details

PMID:24944140
Participants:82
Impact:lower in HTLEF group: 3.3 ± 1.1 vs HTNEF 11.7 ± 0.7 (P < .0001)
Trust score:3/5

collagen turnover biomarkers (MMP1, TIMP1, MMP1/TIMP1 ratio)

1 evidences

In hypertensive patients with heart failure, higher circulating collagen turnover markers were associated with lower left ventricular twist, suggesting loss of myocardial collagen scaffolding is linked to impaired deformation.

Trust comment: Well-defined observational human study with objective imaging and biomarker data but observational design limits causal inference.

Study Details

PMID:24944140
Participants:82
Impact:log TIMP1, log MMP1, and log MMP1/TIMP1 ratio were higher in HTLEF than HTNEF (all P < .0001)
Trust score:3/5

correlation biomarker vs LV twist

1 evidences

In hypertensive patients with heart failure, higher circulating collagen turnover markers were associated with lower left ventricular twist, suggesting loss of myocardial collagen scaffolding is linked to impaired deformation.

Trust comment: Well-defined observational human study with objective imaging and biomarker data but observational design limits causal inference.

Study Details

PMID:24944140
Participants:82
Impact:inverse correlation between log MMP1/TIMP1 and net LV twist (r = −0.43, P < .0001)
Trust score:3/5

Bone density (radiographic)

1 evidences

Prospective randomized (non-blinded) trial comparing autogenous demineralized dentin matrix with bio-collagen membrane versus natural healing after lower third molar extraction; test group showed better probing depth and radiographic bone density but slightly greater early swelling.

Trust comment: Direct clinical use of a bio-collagen membrane was assessed in a randomized trial with adequate sample size though non-blinded allocation and limited reporting details reduce confidence.

Study Details

PMID:39786610
Participants:90
Impact:+14.22 units (Test 135.81 ± 8.73 vs Control 121.59 ± 13.83 at 3 months)
Trust score:3/5

type I collagen expression (gingiva)

1 evidences

Orthodontic force increased markers in gum tissue and fluid over 4 weeks (higher force → higher marker levels).

Trust comment: Moderate-quality clinical study with 74 patients and appropriate biomarker assays, but results are observational biomarker changes without long-term clinical outcomes.

Study Details

PMID:34693434
Participants:74
Impact:increased with orthodontic force (dose-related, highest at 150 g vs 0 g)
Trust score:3/5

type III collagen expression (gingiva)

1 evidences

Orthodontic force increased markers in gum tissue and fluid over 4 weeks (higher force → higher marker levels).

Trust comment: Moderate-quality clinical study with 74 patients and appropriate biomarker assays, but results are observational biomarker changes without long-term clinical outcomes.

Study Details

PMID:34693434
Participants:74
Impact:increased with orthodontic force (dose-related, highest at 150 g vs 0 g)
Trust score:3/5

MMP-2 in gingival crevicular fluid

1 evidences

Orthodontic force increased markers in gum tissue and fluid over 4 weeks (higher force → higher marker levels).

Trust comment: Moderate-quality clinical study with 74 patients and appropriate biomarker assays, but results are observational biomarker changes without long-term clinical outcomes.

Study Details

PMID:34693434
Participants:74
Impact:increased with orthodontic force (2nd and 4th week; dose-related)
Trust score:3/5

left atrial volume index (LAVI)

1 evidences

In patients at risk of heart failure, spironolactone reduced left atrial volume index and NT-proBNP mainly in those with biomarkers indicating lower collagen cross-linking.

Trust comment: Large randomized trial subgroup/interaction analysis with consistent echocardiographic and biomarker data, though interactions are post-hoc and limited to tertile analyses.

Study Details

PMID:34841615
Participants:515
Impact:-1.77 mL/m² (1 month) and -2.52 mL/m² (9 months) with spironolactone vs control in lowest collagen cross-linking tertile
Trust score:4/5

NT-proBNP

1 evidences

In patients at risk of heart failure, spironolactone reduced left atrial volume index and NT-proBNP mainly in those with biomarkers indicating lower collagen cross-linking.

Trust comment: Large randomized trial subgroup/interaction analysis with consistent echocardiographic and biomarker data, though interactions are post-hoc and limited to tertile analyses.

Study Details

PMID:34841615
Participants:515
Impact:-0.47 ng/L (1 month) and -0.31 ng/L (9 months) with spironolactone vs control in lowest collagen cross-linking tertile
Trust score:4/5

CITP:MMP-1 ratio (biomarker of collagen cross-linking)

1 evidences

In patients at risk of heart failure, spironolactone reduced left atrial volume index and NT-proBNP mainly in those with biomarkers indicating lower collagen cross-linking.

Trust comment: Large randomized trial subgroup/interaction analysis with consistent echocardiographic and biomarker data, though interactions are post-hoc and limited to tertile analyses.

Study Details

PMID:34841615
Participants:515
Impact:higher baseline ratio (indicating less cross-linking) associated with greater LAVI reduction with spironolactone (interaction p=0.005)
Trust score:4/5

buccal soft tissue horizontal contour change

1 evidences

Collagen-containing bone grafts showed slightly less buccal soft-tissue loss at 6 months vs other treatments, but differences were not statistically significant.

Trust comment: Randomized controlled clinical trial in 40 patients with objective volumetric measures; small sample and differences were not statistically significant.

Study Details

PMID:24593810
Participants:40
Impact:DBBM-C/CM −1.2 mm; DBBM-C/PG −1.2 mm; ß-TCP −1.7 mm; spontaneous −1.8 mm (6 months; differences NS)
Trust score:4/5

intraocular pressure (IOP) at 48 months

1 evidences

In 104 patients undergoing deep sclerectomy, adding a collagen implant improved long-term intraocular pressure control, increased success rates, and reduced need for glaucoma medications over ~44 months.

Trust comment: Prospective randomized trial with 104 eyes and long follow-up showing consistent benefit of a collagen implant; good sample and clinically meaningful endpoints.

Study Details

PMID:14693783
Participants:104
Impact:DSCI −50% vs DS −40% (mean reduction)
Trust score:4/5

pocket depth reduction (buccal/lingual)

1 evidences

Using bovine porous bone mineral plus a porcine-derived collagen membrane led to greater pocket-depth reduction, attachment gain, and defect fill vs flap debridement at 6 months.

Trust comment: Controlled split‑mouth clinical study with objective re-entry measurements (22 defects); moderate sample size but clinically meaningful differences reported.

Study Details

PMID:11140555
Participants:22
Impact:difference vs control: buccal +1.89 ±0.31 mm; lingual +0.88 ±0.27 mm (favoring collagen membrane group)
Trust score:4/5

clinical attachment gain (buccal/lingual)

1 evidences

Using bovine porous bone mineral plus a porcine-derived collagen membrane led to greater pocket-depth reduction, attachment gain, and defect fill vs flap debridement at 6 months.

Trust comment: Controlled split‑mouth clinical study with objective re-entry measurements (22 defects); moderate sample size but clinically meaningful differences reported.

Study Details

PMID:11140555
Participants:22
Impact:difference vs control: buccal +1.51 ±0.33 mm; lingual +1.50 ±0.35 mm
Trust score:4/5

defect fill (buccal/lingual)

1 evidences

Using bovine porous bone mineral plus a porcine-derived collagen membrane led to greater pocket-depth reduction, attachment gain, and defect fill vs flap debridement at 6 months.

Trust comment: Controlled split‑mouth clinical study with objective re-entry measurements (22 defects); moderate sample size but clinically meaningful differences reported.

Study Details

PMID:11140555
Participants:22
Impact:difference vs control: buccal +2.67 ±0.91 mm; lingual +2.54 ±0.87 mm
Trust score:4/5

recurrence rate

1 evidences

Placing a gentamicin-containing collagen sponge into the wound after pilonidal sinus surgery sped healing and reduced infections and recurrences compared with oral antibiotics alone.

Trust comment: Prospective randomized study with clearly reported clinical outcomes and adequate sample size (80), though numeric effect sizes not provided for each outcome in the text.

Study Details

PMID:20819439
Participants:80
Impact:decreased recurrence rate (significant)
Trust score:4/5

objective cure rate

1 evidences

Collagen-coated transvaginal mesh gave a much higher objective cure rate for anterior wall prolapse at 12 months but had notable mesh exposure complications.

Trust comment: Large multicenter randomized controlled trial with clear primary outcome and reported effect sizes, though there were substantial device-related complications.

Study Details

PMID:24118844
Participants:161
Impact:mesh 88.1% vs colporrhaphy 39.8% (+48.3 percentage points with mesh)
Trust score:5/5

vaginal mesh exposure

1 evidences

Collagen-coated transvaginal mesh gave a much higher objective cure rate for anterior wall prolapse at 12 months but had notable mesh exposure complications.

Trust comment: Large multicenter randomized controlled trial with clear primary outcome and reported effect sizes, though there were substantial device-related complications.

Study Details

PMID:24118844
Participants:161
Impact:mesh exposure in 10 women (13.3%)
Trust score:5/5

dyspareunia

1 evidences

Collagen-coated transvaginal mesh gave a much higher objective cure rate for anterior wall prolapse at 12 months but had notable mesh exposure complications.

Trust comment: Large multicenter randomized controlled trial with clear primary outcome and reported effect sizes, though there were substantial device-related complications.

Study Details

PMID:24118844
Participants:161
Impact:2.7% in mesh group (not significant)
Trust score:5/5

Lysholm score

1 evidences

Use of a lateral collagen meniscus implant improved function, activity and pain scores over 2 years in patients with partial lateral meniscal defects, with some device-related adverse events in a minority.

Trust comment: Multicenter prospective case series with objective outcome measures and 2-year follow-up, but non-randomized Level IV design limits causal inference.

Study Details

PMID:25935606
Participants:43
Impact:improved from 64.3 ± 18.4 to 93.2 ± 7.2 (+28.9 points)
Trust score:3/5

pain (visual analog scale)

1 evidences

Use of a lateral collagen meniscus implant improved function, activity and pain scores over 2 years in patients with partial lateral meniscal defects, with some device-related adverse events in a minority.

Trust comment: Multicenter prospective case series with objective outcome measures and 2-year follow-up, but non-randomized Level IV design limits causal inference.

Study Details

PMID:25935606
Participants:43
Impact:pain during strenuous activity 59 → 14 (−45); routine activity 29 → 3 (−26); at rest 20 → 2 (−18)
Trust score:3/5

patient satisfaction/activity level

1 evidences

Use of a lateral collagen meniscus implant improved function, activity and pain scores over 2 years in patients with partial lateral meniscal defects, with some device-related adverse events in a minority.

Trust comment: Multicenter prospective case series with objective outcome measures and 2-year follow-up, but non-randomized Level IV design limits causal inference.

Study Details

PMID:25935606
Participants:43
Impact:95% satisfied; 58% returned to preinjury activity level at 2 years
Trust score:3/5

corneal rigidity (G value)

1 evidences

Corneal crosslinking sometimes increased corneal rigidity as measured by a Schiøtz tonometer, but results were operator-dependent and variable.

Trust comment: Prospective observational study with reasonable sample but uses an operator-dependent low-tech measure and shows mixed significance across operators.

Study Details

PMID:34011736
Participants:72
Impact:Increase post-CXL (example: operator 2 A-mode mean 0.811→1.064, Δ +0.253, p=0.038, n=20)
Trust score:3/5

corneal rigidity dependence on central corneal thickness (CCT)

1 evidences

Corneal crosslinking sometimes increased corneal rigidity as measured by a Schiøtz tonometer, but results were operator-dependent and variable.

Trust comment: Prospective observational study with reasonable sample but uses an operator-dependent low-tech measure and shows mixed significance across operators.

Study Details

PMID:34011736
Participants:72
Impact:Significant positive association between G and CCT in some modes (no single % given)
Trust score:3/5

primary patency at 8 years

1 evidences

Collagen-coated Dacron aortic grafts had similar long-term patency and complication rates to gelatine-coated Dacron and PTFE grafts over ~8 years.

Trust comment: Large prospective randomized multicenter trial with long follow-up and robust outcomes supporting high trustworthiness.

Study Details

PMID:12874586
Participants:149
Impact:GEL-D 77%, COL-D 78%, PTFE 79% (no significant differences)
Trust score:5/5

secondary corrected patency at 8 years

1 evidences

Collagen-coated Dacron aortic grafts had similar long-term patency and complication rates to gelatine-coated Dacron and PTFE grafts over ~8 years.

Trust comment: Large prospective randomized multicenter trial with long follow-up and robust outcomes supporting high trustworthiness.

Study Details

PMID:12874586
Participants:149
Impact:GEL-D 91%, COL-D 96%, PTFE 90% (no significant differences)
Trust score:5/5

pocket probing depth (PPD)

1 evidences

Both HA/collagen (Biostite) and bovine HA (Bio-Oss) grafts produced similar, significant improvements in pocket depth, clinical attachment, and defect fill at 12 months.

Trust comment: Randomized clinical trial with objective clinical and radiographic endpoints and 12-month follow-up but small sample size limits precision.

Study Details

PMID:15086616
Participants:24
Impact:−4.2 mm (Biostite) and −4.4 mm (Bio-Oss) reduction at 12 months
Trust score:4/5

radiographic defect depth (DEPTH)

1 evidences

Both HA/collagen (Biostite) and bovine HA (Bio-Oss) grafts produced similar, significant improvements in pocket depth, clinical attachment, and defect fill at 12 months.

Trust comment: Randomized clinical trial with objective clinical and radiographic endpoints and 12-month follow-up but small sample size limits precision.

Study Details

PMID:15086616
Participants:24
Impact:+2.5 mm (Biostite) and +3.1 mm (Bio-Oss) gain at 12 months
Trust score:4/5

buccolingual ridge width (HRA)

1 evidences

Porcine-derived xenograft showed equal or better dimensional stability than bovine-derived xenograft in horizontal ridge augmentation and socket preservation at 6 months.

Trust comment: Randomized prospective cohort with small group sizes (n=10 per group); clinically relevant endpoints but limited power.

Study Details

PMID:36305933
Participants:40
Impact:Increase from baseline to 6 months: +2.32 mm (bovine HRA) and +3.00 mm (porcine HRA)
Trust score:3/5

buccolingual width (ESP)

1 evidences

Porcine-derived xenograft showed equal or better dimensional stability than bovine-derived xenograft in horizontal ridge augmentation and socket preservation at 6 months.

Trust comment: Randomized prospective cohort with small group sizes (n=10 per group); clinically relevant endpoints but limited power.

Study Details

PMID:36305933
Participants:40
Impact:Decrease at 6 months: to 5.8 mm (bovine ESP) and 6.61 mm (porcine ESP); porcine had significantly lower dimensional change
Trust score:3/5

bone volume stability

1 evidences

Porcine-derived xenograft showed equal or better dimensional stability than bovine-derived xenograft in horizontal ridge augmentation and socket preservation at 6 months.

Trust comment: Randomized prospective cohort with small group sizes (n=10 per group); clinically relevant endpoints but limited power.

Study Details

PMID:36305933
Participants:40
Impact:Porcine xenograft showed significantly lower dimensional change (more stable) at 6 months in ESP group
Trust score:3/5

primary graft patency (5 years)

1 evidences

Randomized patients received prostheses coated with gelatin, collagen (Hemashield), or albumin; no significant differences in patency or late complications over 5 years.

Trust comment: Prospective randomized study with adequate sample size and long follow-up directly comparing a collagen-coated prosthesis to alternatives.

Study Details

PMID:9859745
Participants:150
Impact:Hemashield (collagen) 91% vs Unigraft 92% and USCI 92% (no significant difference)
Trust score:4/5

secondary patency (5 years)

1 evidences

Randomized patients received prostheses coated with gelatin, collagen (Hemashield), or albumin; no significant differences in patency or late complications over 5 years.

Trust comment: Prospective randomized study with adequate sample size and long follow-up directly comparing a collagen-coated prosthesis to alternatives.

Study Details

PMID:9859745
Participants:150
Impact:Hemashield 95% vs Unigraft 98% and USCI 94% (no significant difference)
Trust score:4/5

late anastomotic aneurysm (groin)

1 evidences

Randomized patients received prostheses coated with gelatin, collagen (Hemashield), or albumin; no significant differences in patency or late complications over 5 years.

Trust comment: Prospective randomized study with adequate sample size and long follow-up directly comparing a collagen-coated prosthesis to alternatives.

Study Details

PMID:9859745
Participants:150
Impact:6% in each group (no difference)
Trust score:4/5

graft healing / failure rate at 6–9 months

1 evidences

Using a collagen membrane to cover sinus grafts improved implant survival, particularly for implants loaded at 6–9 months.

Trust comment: Direct clinical use of a collagen barrier with modest sample size and non-randomized clinical report design; moderate relevance but limited power.

Study Details

PMID:11669254
Participants:29
Impact:fewer failures with collagen membrane when loaded at 6–9 months (qualitative improvement)
Trust score:3/5

daytime interstitial glucose AUC

1 evidences

Four weeks of daily 10 g porcine collagen did not change overall daytime glucose but raised glucose variability and markers of insulin resistance.

Trust comment: Randomized, placebo-controlled trial with continuous glucose monitoring and trial registration; moderate sample size.

Study Details

PMID:39889494
Participants:56
Impact:no significant change (95% CI -5.1 to 30.0 mmol/(L·h); p=0.159)
Trust score:4/5

glycemic variability

1 evidences

Four weeks of daily 10 g porcine collagen did not change overall daytime glucose but raised glucose variability and markers of insulin resistance.

Trust comment: Randomized, placebo-controlled trial with continuous glucose monitoring and trial registration; moderate sample size.

Study Details

PMID:39889494
Participants:56
Impact:increased (SD +0.0–0.2 mmol/L; CONGA-4 +0.1–0.4 mmol/L; MAGE +0.2–1.8 mmol/L; p≤0.036)
Trust score:4/5

insulin resistance (fasting insulin, HOMA-IR, HOMA-β)

1 evidences

Four weeks of daily 10 g porcine collagen did not change overall daytime glucose but raised glucose variability and markers of insulin resistance.

Trust comment: Randomized, placebo-controlled trial with continuous glucose monitoring and trial registration; moderate sample size.

Study Details

PMID:39889494
Participants:56
Impact:increased (fasting insulin p=0.005; HOMA-IR p=0.008; HOMA-β p=0.009)
Trust score:4/5

clinical scores (Lysholm, IKDC, pain)

1 evidences

Collagen meniscus implant plus osteotomy showed similar clinical scores to osteotomy alone at 2 years, with one implant dislocation reported.

Trust comment: Prospective randomized study but substantial loss to follow-up (60 enrolled → 39 assessed at 24 months) limiting robustness.

Study Details

PMID:17171330
Participants:39
Impact:no significant differences between CMI+osteotomy and osteotomy alone at 24 months (n=39)
Trust score:3/5

implant removal

1 evidences

Collagen meniscus implant plus osteotomy showed similar clinical scores to osteotomy alone at 2 years, with one implant dislocation reported.

Trust comment: Prospective randomized study but substantial loss to follow-up (60 enrolled → 39 assessed at 24 months) limiting robustness.

Study Details

PMID:17171330
Participants:39
Impact:one CMI removed due to dislocation (1/60 total treated)
Trust score:3/5

complete success rate (IOP <21 mm Hg without meds) at 48 months

1 evidences

In 104 patients undergoing deep sclerectomy, adding a collagen implant improved long-term intraocular pressure control, increased success rates, and reduced need for glaucoma medications over ~44 months.

Trust comment: Prospective randomized trial with 104 eyes and long follow-up showing consistent benefit of a collagen implant; good sample and clinically meaningful endpoints.

Study Details

PMID:14693783
Participants:104
Impact:DSCI 63.4% vs DS 34.6%
Trust score:4/5

mean number of glaucoma medications

1 evidences

In 104 patients undergoing deep sclerectomy, adding a collagen implant improved long-term intraocular pressure control, increased success rates, and reduced need for glaucoma medications over ~44 months.

Trust comment: Prospective randomized trial with 104 eyes and long follow-up showing consistent benefit of a collagen implant; good sample and clinically meaningful endpoints.

Study Details

PMID:14693783
Participants:104
Impact:DSCI reduced from 2.2 to 0.4 vs DS 2.1 to 1.0 (p=0.001)
Trust score:4/5

knee ROM flexion (active)

1 evidences

In 96 active adults with activity-related knee discomfort, 40 mg daily undenatured type II collagen (UC-II) for 24 weeks modestly improved knee flexion range of motion versus placebo and was well tolerated.

Trust comment: Multicenter randomized double-blind placebo-controlled trial (n=96) with registered protocol and statistically significant improvement in ROM flexion, though effect size is modest and population is limited to active subjects with activity-related discomfort.

Study Details

PMID:35377244
Participants:96
Impact:+3.23° (UC-II) vs +0.21° (placebo) at 24 weeks; p=0.025
Trust score:4/5

knee ROM extension (active)

1 evidences

In 96 active adults with activity-related knee discomfort, 40 mg daily undenatured type II collagen (UC-II) for 24 weeks modestly improved knee flexion range of motion versus placebo and was well tolerated.

Trust comment: Multicenter randomized double-blind placebo-controlled trial (n=96) with registered protocol and statistically significant improvement in ROM flexion, though effect size is modest and population is limited to active subjects with activity-related discomfort.

Study Details

PMID:35377244
Participants:96
Impact:+2.21° (UC-II) vs +1.27° (placebo) at 24 weeks (between-group p>0.05)
Trust score:4/5

Safety/tolerability

2 evidences

Oral bovine type I collagen did not improve skin scores overall in diffuse cutaneous systemic sclerosis, but a late-phase subgroup showed greater skin score improvement at month 15.

Trust comment: Large randomized double-blind placebo-controlled trial directly testing oral type I collagen; overall null primary result but credible subgroup signal—well conducted though subgroup finding is exploratory.

Study Details

PMID:18512816
Participants:168
Impact:well tolerated (no major safety signal reported)
Trust score:4/5

In 96 active adults with activity-related knee discomfort, 40 mg daily undenatured type II collagen (UC-II) for 24 weeks modestly improved knee flexion range of motion versus placebo and was well tolerated.

Trust comment: Multicenter randomized double-blind placebo-controlled trial (n=96) with registered protocol and statistically significant improvement in ROM flexion, though effect size is modest and population is limited to active subjects with activity-related discomfort.

Study Details

PMID:35377244
Participants:96
Impact:well tolerated; no product-related adverse events reported
Trust score:4/5

urinary type I collagen N-telopeptide (bone resorption marker)

1 evidences

In healthy adults, 8 weeks of high-dose simvastatin (80 mg/day) lowered a serum bone formation marker but did not change a urinary collagen resorption marker.

Trust comment: Randomized trial in 55 healthy adults with clear marker measurements but small sample and short duration.

Study Details

PMID:16088363
Participants:55
Impact:no change
Trust score:3/5

incontinence score

1 evidences

Endoscopic collagen injections provided little improvement for stress urinary incontinence compared with autologous cell injections; most women treated with collagen remained incontinent at 12 months.

Trust comment: Randomized controlled trial in humans directly testing collagen injections; modest sample size but clear outcomes.

Study Details

PMID:17604800
Participants:63
Impact:median remained 6.0 (no improvement)
Trust score:4/5

rhabdosphincter thickness

1 evidences

Endoscopic collagen injections provided little improvement for stress urinary incontinence compared with autologous cell injections; most women treated with collagen remained incontinent at 12 months.

Trust comment: Randomized controlled trial in humans directly testing collagen injections; modest sample size but clear outcomes.

Study Details

PMID:17604800
Participants:63
Impact:+0.19 mm (2.13 mm baseline → 2.32 mm in collagen group)
Trust score:4/5

rhabdosphincter contractility

1 evidences

Endoscopic collagen injections provided little improvement for stress urinary incontinence compared with autologous cell injections; most women treated with collagen remained incontinent at 12 months.

Trust comment: Randomized controlled trial in humans directly testing collagen injections; modest sample size but clear outcomes.

Study Details

PMID:17604800
Participants:63
Impact:+0.09 mm (0.58 mm baseline → 0.67 mm in collagen group)
Trust score:4/5

Cbfa1/Runx2 expression (osteoblastic activity)

1 evidences

Biopsies from extraction sockets (some augmented with Bio-Oss collagen) showed peak osteoblastic activity at 4 weeks with reduced mature osteoblast markers and vascularity by 12 weeks.

Trust comment: Small human histological study including Bio-Oss collagen augmentation; descriptive immunohistochemistry with limited clinical endpoints.

Study Details

PMID:22462496
Participants:33
Impact:median 56% at 4 weeks → 61% at 12 weeks (+5 percentage points)
Trust score:3/5

osteocalcin expression (mature osteoblast marker)

1 evidences

Biopsies from extraction sockets (some augmented with Bio-Oss collagen) showed peak osteoblastic activity at 4 weeks with reduced mature osteoblast markers and vascularity by 12 weeks.

Trust comment: Small human histological study including Bio-Oss collagen augmentation; descriptive immunohistochemistry with limited clinical endpoints.

Study Details

PMID:22462496
Participants:33
Impact:median 21% at 4 weeks → 9% at 12 weeks (−12 percentage points)
Trust score:3/5

vascularity (CD31 score)

1 evidences

Biopsies from extraction sockets (some augmented with Bio-Oss collagen) showed peak osteoblastic activity at 4 weeks with reduced mature osteoblast markers and vascularity by 12 weeks.

Trust comment: Small human histological study including Bio-Oss collagen augmentation; descriptive immunohistochemistry with limited clinical endpoints.

Study Details

PMID:22462496
Participants:33
Impact:median score 5 at 4 weeks → 3 at 12 weeks (−2 score points)
Trust score:3/5

wound healing / full recovery time

1 evidences

Use of a gentamicin-impregnated collagen sponge after marsupialization did not reduce infection, hemorrhage, or healing time compared with control.

Trust comment: Prospective randomized trial directly testing a collagen sponge product but small sample and negative findings.

Study Details

PMID:25711716
Participants:50
Impact:29.6 days (control) vs 28.2 days (collagen) (−1.4 days, not significant)
Trust score:3/5

hemorrhage / excessive granulation

1 evidences

Use of a gentamicin-impregnated collagen sponge after marsupialization did not reduce infection, hemorrhage, or healing time compared with control.

Trust comment: Prospective randomized trial directly testing a collagen sponge product but small sample and negative findings.

Study Details

PMID:25711716
Participants:50
Impact:no significant difference
Trust score:3/5

number of glaucoma medications

2 evidences

Collagen implants in deep sclerectomy produced intraocular pressure lowering and medication reduction comparable to a PMMA implant—no significant differences between implants.

Trust comment: Randomized controlled trial directly comparing collagen implant to alternative with mid-sized sample and extended follow-up; results robust for device comparison.

Study Details

PMID:16778652
Participants:60
Impact:2.4 → 0.7 (−1.7 medications)
Trust score:4/5

Randomized study of nonpenetrating deep sclerectomy with a collagen implant, comparing adjunctive mitomycin C versus no MMC in glaucoma patients.

Trust comment: Small randomized trial (n=26) with 24-month follow-up but limited sample size reduces generalizability.

Study Details

PMID:14750756
Participants:26
Impact:decreased after surgery (no absolute values reported)
Trust score:3/5

success rate without medication (IOP ≤ 21 mmHg)

1 evidences

Collagen implants in deep sclerectomy produced intraocular pressure lowering and medication reduction comparable to a PMMA implant—no significant differences between implants.

Trust comment: Randomized controlled trial directly comparing collagen implant to alternative with mid-sized sample and extended follow-up; results robust for device comparison.

Study Details

PMID:16778652
Participants:60
Impact:44% (collagen group)
Trust score:4/5

CTX (C-terminal telopeptide of type I collagen)

2 evidences

In 77 men with bone-metastatic prostate cancer on zoledronic acid, most bone turnover markers fell after treatment; several markers were higher in patients with progressive bone disease.

Trust comment: Prospective serial biomarker study with defined clinical endpoints and reasonable sample size, but observational comparisons within treated patients limit causal claims.

Study Details

PMID:17321667
Participants:77
Impact:showed the greatest decrease after zoledronic acid
Trust score:4/5

In 45 postmenopausal osteopenic women, a 12-week supervised walking program improved function and increased bone turnover markers (P1NP, CTX) with osteocalcin rising in the exercise group; both groups received vitamin D and calcium.

Trust comment: Randomized controlled single-blind trial with objective laboratory outcomes; confounded by universal vitamin D/calcium supplementation and modest sample size.

Study Details

PMID:40259282
Participants:45
Impact:Increased +2.4 ng/ml (exercise; p=0.002); increased +4.2 ng/ml (control; p=0.001)
Trust score:4/5

type I/III collagen turnover markers

1 evidences

In 27 children, halving inhaled steroid dose and adding formoterol sped short-term leg growth and increased collagen turnover markers without worsening asthma control.

Trust comment: Randomized double-blind crossover RCT in children with objective collagen marker and growth endpoints, but small sample size.

Study Details

PMID:10999872
Participants:27
Impact:increase (statistically significant during formoterol + lower-dose budesonide)
Trust score:4/5

asthma control

1 evidences

In 27 children, halving inhaled steroid dose and adding formoterol sped short-term leg growth and increased collagen turnover markers without worsening asthma control.

Trust comment: Randomized double-blind crossover RCT in children with objective collagen marker and growth endpoints, but small sample size.

Study Details

PMID:10999872
Participants:27
Impact:no significant change
Trust score:4/5

bone turnover markers (overall)

1 evidences

In 50 elderly men, 6 months of raloxifene showed no overall change in bone turnover or lipids, but reductions in urinary type I collagen NTX occurred in a subset with low baseline estradiol.

Trust comment: Randomized blinded study with clear biomarker outcomes and moderate sample size, but subgroup-dependent effects.

Study Details

PMID:11697809
Participants:50
Impact:no significant change vs placebo
Trust score:4/5

serum sex steroids / lipids

1 evidences

In 50 elderly men, 6 months of raloxifene showed no overall change in bone turnover or lipids, but reductions in urinary type I collagen NTX occurred in a subset with low baseline estradiol.

Trust comment: Randomized blinded study with clear biomarker outcomes and moderate sample size, but subgroup-dependent effects.

Study Details

PMID:11697809
Participants:50
Impact:no significant change
Trust score:4/5

responder rate (≥50% wound area reduction by week 4)

1 evidences

In patients with diabetic foot ulcers, topical collagen/ORC/silver increased early healing responders and reduced withdrawals for infection versus standard care.

Trust comment: Randomized clinical trial with meaningful clinical endpoints but relatively small sample size.

Study Details

PMID:23438054
Participants:39
Impact:79% (collagen/ORC/silver) vs 43% (control); p=0.035
Trust score:4/5

withdrawals due to infection

1 evidences

In patients with diabetic foot ulcers, topical collagen/ORC/silver increased early healing responders and reduced withdrawals for infection versus standard care.

Trust comment: Randomized clinical trial with meaningful clinical endpoints but relatively small sample size.

Study Details

PMID:23438054
Participants:39
Impact:0% (collagen/ORC/silver) vs 31% (control); p=0.012
Trust score:4/5

combined protease (MMP-9 + elastase) concentration

1 evidences

In patients with diabetic foot ulcers, topical collagen/ORC/silver increased early healing responders and reduced withdrawals for infection versus standard care.

Trust comment: Randomized clinical trial with meaningful clinical endpoints but relatively small sample size.

Study Details

PMID:23438054
Participants:39
Impact:higher in nonresponders than responders at week 4 (p=0.012)
Trust score:4/5

newly formed bone fraction

1 evidences

In 40 patients undergoing sinus augmentation, covering the lateral window with a collagen membrane produced comparable bone formation, surgical outcomes, and patient discomfort to bony wall repositioning.

Trust comment: Prospective randomized clinical and histological study with complete clinical follow-up but loss of 11/40 biopsies for histology.

Study Details

PMID:35593928
Participants:40
Impact:27.8% ± 11.2% (bony wall) vs 30.3% ± 4.5% (collagen membrane); no significant difference
Trust score:4/5

KOOS pain and function

1 evidences

In 144 randomized patients, chondrocyte implantation on a porcine collagen membrane (MACI) produced sustained superior pain and function outcomes at 5 years versus microfracture for symptomatic knee cartilage defects.

Trust comment: Large multicenter randomized trial with 5-year follow-up and clinically relevant endpoints using a collagen membrane scaffold.

Study Details

PMID:29565642
Participants:144
Impact:MACI > microfracture at 5 years; clinically and statistically significant (co-primary endpoint p=0.022)
Trust score:5/5

activities of daily living (KOOS ADL)

1 evidences

In 144 randomized patients, chondrocyte implantation on a porcine collagen membrane (MACI) produced sustained superior pain and function outcomes at 5 years versus microfracture for symptomatic knee cartilage defects.

Trust comment: Large multicenter randomized trial with 5-year follow-up and clinically relevant endpoints using a collagen membrane scaffold.

Study Details

PMID:29565642
Participants:144
Impact:statistically significantly better with MACI (p=0.007)
Trust score:5/5

MRI structural repair (defect filling)

1 evidences

In 144 randomized patients, chondrocyte implantation on a porcine collagen membrane (MACI) produced sustained superior pain and function outcomes at 5 years versus microfracture for symptomatic knee cartilage defects.

Trust comment: Large multicenter randomized trial with 5-year follow-up and clinically relevant endpoints using a collagen membrane scaffold.

Study Details

PMID:29565642
Participants:144
Impact:improvement in both groups; no significant difference between MACI and microfracture
Trust score:5/5

disability (ODI)

1 evidences

Stentoplasty using resorbable calcium-salt bone fillers in older adults with a single vertebral compression fracture reduced pain and disability and promoted bone formation over 3 years, with slight early loss of restored vertebral height.

Trust comment: Prospective randomized human trial with 3-year follow-up and objective radiological measures, but modest sample size (42) limits generalizability.

Study Details

PMID:34040361
Participants:42
Impact:Group B ODI decreased from 81.36 to 34.00 post-op (−47.36 points)
Trust score:4/5

osteogenesis (CT value inside VBS)

1 evidences

Stentoplasty using resorbable calcium-salt bone fillers in older adults with a single vertebral compression fracture reduced pain and disability and promoted bone formation over 3 years, with slight early loss of restored vertebral height.

Trust comment: Prospective randomized human trial with 3-year follow-up and objective radiological measures, but modest sample size (42) limits generalizability.

Study Details

PMID:34040361
Participants:42
Impact:Group B CT value increased from 52.21 HU post-op to 146.79 HU at 1 year (+94.58 HU)
Trust score:4/5

serum pre-albumin

1 evidences

Randomized double-blind pilot trial in men with 20–30% TBSA burns testing an oral hydrolyzed collagen supplement versus isocaloric placebo for 4 weeks; supplement improved markers and wound-healing rate.

Trust comment: Randomized double-blind human pilot trial with objective biochemical and clinical endpoints, though small and limited to men.

Study Details

PMID:31859087
Participants:31
Impact:Week 2: 29.7 vs 17.8 mg/dL (+11.9 mg/dL); Week 4: 35.1 vs 28.3 mg/dL (+6.8 mg/dL) (collagen > control)
Trust score:4/5

rate of wound healing

1 evidences

Randomized double-blind pilot trial in men with 20–30% TBSA burns testing an oral hydrolyzed collagen supplement versus isocaloric placebo for 4 weeks; supplement improved markers and wound-healing rate.

Trust comment: Randomized double-blind human pilot trial with objective biochemical and clinical endpoints, though small and limited to men.

Study Details

PMID:31859087
Participants:31
Impact:Hazard ratio 3.7 for healing with collagen vs control (95% CI 1.434–9.519)
Trust score:4/5

aqueous tear volume (Schirmer I)

1 evidences

Prospective randomized trial comparing collagen versus silicone punctal plugs for dry eye; both plug types produced similar short-term improvements in tear metrics and retention.

Trust comment: Prospective randomized clinical trial with clear objective measures but small sample and short-term follow-up.

Study Details

PMID:15939391
Participants:24
Impact:significant improvement after collagen plug insertion (post-insertion values improved)
Trust score:3/5

tear film stability (tear break-up time)

1 evidences

Prospective randomized trial comparing collagen versus silicone punctal plugs for dry eye; both plug types produced similar short-term improvements in tear metrics and retention.

Trust comment: Prospective randomized clinical trial with clear objective measures but small sample and short-term follow-up.

Study Details

PMID:15939391
Participants:24
Impact:significant improvement after collagen plug insertion
Trust score:3/5

ocular surface retention (T1/2 and RI)

1 evidences

Prospective randomized trial comparing collagen versus silicone punctal plugs for dry eye; both plug types produced similar short-term improvements in tear metrics and retention.

Trust comment: Prospective randomized clinical trial with clear objective measures but small sample and short-term follow-up.

Study Details

PMID:15939391
Participants:24
Impact:T1/2 and RI increased significantly after collagen plug insertion; post-insertion values similar to silicone
Trust score:3/5

fusiforms (subgingival)

1 evidences

Clinical study evaluating a single topical device composed of 95% collagen + 5% metronidazole as adjunct to debridement in adult periodontitis patients, showing reductions in several microbial measures.

Trust comment: Controlled clinical study with microbiological endpoints and 30 patients, but single application and limited outcome reporting.

Study Details

PMID:9249631
Participants:30
Impact:significant decrease after collagen/metronidazole device
Trust score:3/5

Actinobacillus actinomycetemcomitans (Aa) positive sites

1 evidences

Clinical study evaluating a single topical device composed of 95% collagen + 5% metronidazole as adjunct to debridement in adult periodontitis patients, showing reductions in several microbial measures.

Trust comment: Controlled clinical study with microbiological endpoints and 30 patients, but single application and limited outcome reporting.

Study Details

PMID:9249631
Participants:30
Impact:fewer Aa-positive sites in test group (13/25 after treatment)
Trust score:3/5

total anaerobically cultivable bacteria (TA) and black-pigmented anaerobes (BPA)

1 evidences

Clinical study evaluating a single topical device composed of 95% collagen + 5% metronidazole as adjunct to debridement in adult periodontitis patients, showing reductions in several microbial measures.

Trust comment: Controlled clinical study with microbiological endpoints and 30 patients, but single application and limited outcome reporting.

Study Details

PMID:9249631
Participants:30
Impact:decreases observed (not all reported as statistically significant)
Trust score:3/5

gingival index

1 evidences

Randomized comparative study (n=45; 3 groups of 15) testing periodontal dressings: collagen dressing showed greater symptomatic relief and improved clinical wound-healing indices versus light-cure and non-eugenol dressings.

Trust comment: Randomized study with 45 patients showing clinical benefit of collagen dressing, but limited sample size and incomplete reporting reduce strength of evidence.

Study Details

PMID:31797844
Participants:45
Impact:group I (collagen dressing) decreased from 1.40 ±0.14 to 1.10 ±0.30 (improvement)
Trust score:3/5

probing depth

2 evidences

Using deproteinised bovine bone mineral plus a resorbable collagen membrane after impacted third molar extraction improved alveolar bone dimensions and periodontal status versus natural healing.

Trust comment: Randomized clinical study with 99 patients and statistically significant outcomes reported, though effect sizes not fully detailed.

Study Details

PMID:37522232
Participants:99
Impact:reduced postoperatively in both groups (post-op decrease reported)
Trust score:4/5

Randomized comparative study (n=45; 3 groups of 15) testing periodontal dressings: collagen dressing showed greater symptomatic relief and improved clinical wound-healing indices versus light-cure and non-eugenol dressings.

Trust comment: Randomized study with 45 patients showing clinical benefit of collagen dressing, but limited sample size and incomplete reporting reduce strength of evidence.

Study Details

PMID:31797844
Participants:45
Impact:significant reduction reported for collagen dressing group (value not specified)
Trust score:3/5

root coverage (CPRT)

1 evidences

Comparative clinical study (1-year) showing collagen-containing regenerative technique (CPRT) achieved high root coverage and increased gingival thickness versus GTR.

Trust comment: Well-conducted clinical comparative study with 1-year follow-up and clear outcomes, though moderate sample size.

Study Details

PMID:11846201
Participants:45
Impact:87.12% mean root coverage
Trust score:4/5

complete root coverage (CPRT)

1 evidences

Comparative clinical study (1-year) showing collagen-containing regenerative technique (CPRT) achieved high root coverage and increased gingival thickness versus GTR.

Trust comment: Well-conducted clinical comparative study with 1-year follow-up and clear outcomes, though moderate sample size.

Study Details

PMID:11846201
Participants:45
Impact:53.3% of cases complete coverage
Trust score:4/5

gingival thickness (GT) increase

1 evidences

Comparative clinical study (1-year) showing collagen-containing regenerative technique (CPRT) achieved high root coverage and increased gingival thickness versus GTR.

Trust comment: Well-conducted clinical comparative study with 1-year follow-up and clear outcomes, though moderate sample size.

Study Details

PMID:11846201
Participants:45
Impact:significantly greater GT increase with CPRT vs GTR (P<0.01)
Trust score:4/5

probing attachment gain

1 evidences

In periodontal intraosseous defects, adding a collagen membrane to enamel matrix protein therapy did not improve clinical or radiographic outcomes compared with either therapy alone.

Trust comment: Moderate-sized clinical comparative study directly testing a collagen membrane; randomized status unclear and sample modest, but outcomes are clinical and relevant.

Study Details

PMID:12516831
Participants:61
Impact:No significant difference between combined therapy and either monotherapy at 6 months and 1 year
Trust score:3/5

postoperative blood loss (drainage blood)

1 evidences

Collagen hemostatic sponge reduced postoperative bleeding, transfusions, and hospital stay versus gelatin sponge; topical TXA reduced bleeding more than collagen.

Trust comment: Prospective randomized controlled trial with 120 patients and objective measured outcomes; moderate quality.

Study Details

PMID:29110696
Participants:120
Impact:total drainage blood 114.4±60.7 ml vs control 160.2±82.8 ml (≈−28.8%)
Trust score:4/5

hospital stay length

1 evidences

Collagen hemostatic sponge reduced postoperative bleeding, transfusions, and hospital stay versus gelatin sponge; topical TXA reduced bleeding more than collagen.

Trust comment: Prospective randomized controlled trial with 120 patients and objective measured outcomes; moderate quality.

Study Details

PMID:29110696
Participants:120
Impact:6.09±1.3 days vs 7.82±1.2 days (≈−1.73 days)
Trust score:4/5

Collagen deposition area

1 evidences

In adults with gastric ulcer, adding hydrotalcite to esomeprazole improved tissue maturity with greater collagen deposition and markers of angiogenesis versus esomeprazole alone.

Trust comment: Randomized clinical observation with histologic endpoints and clear differences but relatively small sample (24 per treatment group).

Study Details

PMID:28275307
Participants:72
Impact:+92% (combination 260909.51 vs monotherapy 135700.75; combination > monotherapy, p<0.05)
Trust score:4/5

Hydroxyproline content

1 evidences

In adults with gastric ulcer, adding hydrotalcite to esomeprazole improved tissue maturity with greater collagen deposition and markers of angiogenesis versus esomeprazole alone.

Trust comment: Randomized clinical observation with histologic endpoints and clear differences but relatively small sample (24 per treatment group).

Study Details

PMID:28275307
Participants:72
Impact:+55% (combination 1909.53 ng/mL vs monotherapy 1235.32 ng/mL; p<0.05)
Trust score:4/5

Angiogenesis (Factor VIII–positive cells)

1 evidences

In adults with gastric ulcer, adding hydrotalcite to esomeprazole improved tissue maturity with greater collagen deposition and markers of angiogenesis versus esomeprazole alone.

Trust comment: Randomized clinical observation with histologic endpoints and clear differences but relatively small sample (24 per treatment group).

Study Details

PMID:28275307
Participants:72
Impact:+17% (combination 33.54 vs monotherapy 28.58 cells; p<0.05)
Trust score:4/5

Bone resorption (NTx)

1 evidences

Randomized trial of two whole-body vibration frequencies (20 Hz vs 30 Hz) in chronic stroke patients; both increased knee strength and reduced bone resorption (NTx), with 30 Hz showing greater paretic eccentric strength gains.

Trust comment: Well-powered randomized trial with blinded assessors and intention-to-treat analysis, though no sham control and limited generalizability beyond sample.

Study Details

PMID:33420277
Participants:80
Impact:decreased: ~36% reduction (20 Hz) and ~43% reduction (30 Hz) from baseline
Trust score:4/5

Complete success rate (IOP ≤18 mmHg without medication)

1 evidences

In patients with open-angle glaucoma, very deep sclerectomy with a collagen implant provided good IOP control similar to standard deep sclerectomy over 2 years, with lower day-1 IOP in the very deep method.

Trust comment: Single-masked randomized controlled trial with adequate follow-up (mean ~19 months) though moderate sample size (48 patients).

Study Details

PMID:19373103
Participants:48
Impact:57% (VDSCI) vs 62% (DSCI) (no significant difference)
Trust score:4/5

Filtering bleb/intrascleral volumes

1 evidences

In patients with open-angle glaucoma, very deep sclerectomy with a collagen implant provided good IOP control similar to standard deep sclerectomy over 2 years, with lower day-1 IOP in the very deep method.

Trust comment: Single-masked randomized controlled trial with adequate follow-up (mean ~19 months) though moderate sample size (48 patients).

Study Details

PMID:19373103
Participants:48
Impact:No significant differences in bleb or intrascleral space volumes at 12 months (NS)
Trust score:4/5

Hepatic collagen area

1 evidences

In this phase II randomized trial, oltipraz treatment showed no significant overall histological benefit versus placebo, though the 60 mg bid group showed a trend toward decreased hepatic collagen area and plasma TGF-β1 that correlated with histologic improvement.

Trust comment: Double-blind, placebo-controlled phase II trial with modest sample size and per-protocol analysis; findings were largely non-significant but biologically plausible trends observed.

Study Details

PMID:21492164
Participants:68
Impact:Trend toward decrease in oltipraz 60 mg bid group (no significant between-group differences at 24 weeks)
Trust score:3/5

Plasma TGF-β1

1 evidences

In this phase II randomized trial, oltipraz treatment showed no significant overall histological benefit versus placebo, though the 60 mg bid group showed a trend toward decreased hepatic collagen area and plasma TGF-β1 that correlated with histologic improvement.

Trust comment: Double-blind, placebo-controlled phase II trial with modest sample size and per-protocol analysis; findings were largely non-significant but biologically plausible trends observed.

Study Details

PMID:21492164
Participants:68
Impact:Trend decrease in 60 mg bid group; reductions correlated with improvements in Ishak fibrosis score
Trust score:3/5

Histological fibrosis (Ishak score)

1 evidences

In this phase II randomized trial, oltipraz treatment showed no significant overall histological benefit versus placebo, though the 60 mg bid group showed a trend toward decreased hepatic collagen area and plasma TGF-β1 that correlated with histologic improvement.

Trust comment: Double-blind, placebo-controlled phase II trial with modest sample size and per-protocol analysis; findings were largely non-significant but biologically plausible trends observed.

Study Details

PMID:21492164
Participants:68
Impact:No significant differences among treatment groups at 24 weeks
Trust score:3/5

Refractive error (MRSE)

1 evidences

Adding prophylactic high-fluence corneal collagen crosslinking to high-myopic LASIK improved refractive and keratometric stability over two years compared with LASIK alone.

Trust comment: Prospective randomized comparative study with reasonable sample size but single-center/private-practice setting and potential conflicts of interest noted.

Study Details

PMID:26287881
Participants:140
Impact:Good postoperative MRSE in LASIK-CXL (−0.18 D) and LASIK-only (−0.32 D); both groups had high predictability
Trust score:3/5

Refraction/visual acuity outcomes (20/20 and 20/25 rates)

1 evidences

Adding prophylactic high-fluence corneal collagen crosslinking to high-myopic LASIK improved refractive and keratometric stability over two years compared with LASIK alone.

Trust comment: Prospective randomized comparative study with reasonable sample size but single-center/private-practice setting and potential conflicts of interest noted.

Study Details

PMID:26287881
Participants:140
Impact:Significantly better proportions at 20/20 and 20/25 with LASIK-CXL (p=0.045 and p=0.039)
Trust score:3/5

Keratometric stability

1 evidences

Adding prophylactic high-fluence corneal collagen crosslinking to high-myopic LASIK improved refractive and keratometric stability over two years compared with LASIK alone.

Trust comment: Prospective randomized comparative study with reasonable sample size but single-center/private-practice setting and potential conflicts of interest noted.

Study Details

PMID:26287881
Participants:140
Impact:Improved keratometric stability with LASIK-CXL vs LASIK alone over 2 years
Trust score:3/5

Collagen fiber histology

1 evidences

In this randomized, double-blind trial, MAL plus red light increased dermal thickness and showed trends toward improved collagen and elastic tissue histology in photodamaged facial skin, though between-group differences were often non-significant, possibly due to low power.

Trust comment: Double-blind randomized trial with histological endpoints but limited power (38 samples analyzed) leading to mostly non-significant between-group differences.

Study Details

PMID:22582911
Participants:38
Impact:Histological improvement seen after MAL + red light (trend; differences vs placebo not statistically significant)
Trust score:4/5

Perifollicular fibrosis and elastic tissue

1 evidences

In this randomized, double-blind trial, MAL plus red light increased dermal thickness and showed trends toward improved collagen and elastic tissue histology in photodamaged facial skin, though between-group differences were often non-significant, possibly due to low power.

Trust comment: Double-blind randomized trial with histological endpoints but limited power (38 samples analyzed) leading to mostly non-significant between-group differences.

Study Details

PMID:22582911
Participants:38
Impact:Improvement trends observed post-treatment but not statistically significant between groups
Trust score:4/5

ACR20 response rate

1 evidences

In patients with active rheumatoid arthritis, oral chicken type II collagen (CCII) was effective but less so than methotrexate (MTX) over 24 weeks and was associated with fewer and milder adverse events.

Trust comment: Large randomized, double-blind multicenter trial with good completion rate (89%); CCII was less effective than standard MTX but better tolerated.

Study Details

PMID:18576295
Participants:211
Impact:68.57% (CCII) vs 83.02% (MTX); CCII lower (p<0.05)
Trust score:4/5

ACR50 response rate

1 evidences

In patients with active rheumatoid arthritis, oral chicken type II collagen (CCII) was effective but less so than methotrexate (MTX) over 24 weeks and was associated with fewer and milder adverse events.

Trust comment: Large randomized, double-blind multicenter trial with good completion rate (89%); CCII was less effective than standard MTX but better tolerated.

Study Details

PMID:18576295
Participants:211
Impact:40.95% (CCII) vs 57.54% (MTX); CCII lower (p<0.05)
Trust score:4/5

Marginal bone loss at implant

1 evidences

Use of a collagen membrane (Bio-Gide) in ridge augmentation did not meaningfully change marginal gingiva or marginal bone levels or implant survival during the first year.

Trust comment: Randomized clinical trial with a substantial sample (93) and standardized radiographic/clinical measures; one-year follow-up limits long-term inference.

Study Details

PMID:19040446
Participants:93
Impact:+0.14 mm (mesial) and +0.14 mm (distal) between 1 and 12 months
Trust score:4/5

Marginal gingiva level (MGL)

1 evidences

Use of a collagen membrane (Bio-Gide) in ridge augmentation did not meaningfully change marginal gingiva or marginal bone levels or implant survival during the first year.

Trust comment: Randomized clinical trial with a substantial sample (93) and standardized radiographic/clinical measures; one-year follow-up limits long-term inference.

Study Details

PMID:19040446
Participants:93
Impact:Mesial +0.24 mm; Distal +0.25 mm; Buccal −0.11 mm (changes reported)
Trust score:4/5

Cartilage quality (MOCART score)

1 evidences

Adding atelocollagen to arthroscopic microfracture improved MRI-assessed cartilage quality and yielded hyaline-like cartilage with abundant type II collagen; pain and functional scores improved in both groups with no significant between-group clinical differences at 2 years.

Trust comment: Multicenter, registered randomized controlled trial with blinded imaging assessment and validated outcomes; moderate analyzed sample after dropouts and relatively short (2-year) follow-up.

Study Details

PMID:33143647
Participants:45
Impact:Group1 64.49±18.27 vs Group2 53.01±12.14; +11.48 points (p=0.018)
Trust score:4/5

Pain (100-mm VAS) improvement from baseline

1 evidences

Adding atelocollagen to arthroscopic microfracture improved MRI-assessed cartilage quality and yielded hyaline-like cartilage with abundant type II collagen; pain and functional scores improved in both groups with no significant between-group clinical differences at 2 years.

Trust comment: Multicenter, registered randomized controlled trial with blinded imaging assessment and validated outcomes; moderate analyzed sample after dropouts and relatively short (2-year) follow-up.

Study Details

PMID:33143647
Participants:45
Impact:Group1 −34.59 mm; Group2 −39.74 mm (both significant vs baseline; between-group p=0.72)
Trust score:4/5

Histology — type II collagen in regenerated cartilage

1 evidences

Adding atelocollagen to arthroscopic microfracture improved MRI-assessed cartilage quality and yielded hyaline-like cartilage with abundant type II collagen; pain and functional scores improved in both groups with no significant between-group clinical differences at 2 years.

Trust comment: Multicenter, registered randomized controlled trial with blinded imaging assessment and validated outcomes; moderate analyzed sample after dropouts and relatively short (2-year) follow-up.

Study Details

PMID:33143647
Participants:45
Impact:Abundant type II collagen with hyaline-like appearance in atelocollagen group biopsies
Trust score:4/5

PICP (type I collagen synthesis marker)

1 evidences

In women taking monophasic oral contraceptives, a transient decrease in a type I collagen synthesis marker (PICP) was observed with the lower-ethinyl-estradiol formulation after three cycles and normalized by six months; degradation marker (ICTP) was unchanged.

Trust comment: Controlled human study measuring validated collagen metabolism biomarkers in 60 women; limited by short duration and modest sample size.

Study Details

PMID:12001776
Participants:60
Impact:Transient decrease after three cycles with 20 µg EE + 150 µg DSG, returned to baseline by 6 months; no significant change with 30 µg EE regimen
Trust score:3/5

uCTX-II (urine C-telopeptide of type II collagen)

1 evidences

Oral and transdermal postmenopausal estrogen therapy decreased a urine cartilage-degradation marker (uCTX-II) by ~19–30% after 1 year and strongly suppressed bone resorption marker (uCTX-I), suggesting protective effects on cartilage and bone.

Trust comment: Randomized, double-blind, placebo-controlled trials with 171 completers and validated biochemical and BMD endpoints; robust design though longer-term clinical OA outcomes not provided.

Study Details

PMID:15542048
Participants:171
Impact:Decrease of ~19–30% after 1 year vs placebo (P=0.02 and P=0.003)
Trust score:4/5

uCTX-I (urine C-telopeptide of type I collagen)

1 evidences

Oral and transdermal postmenopausal estrogen therapy decreased a urine cartilage-degradation marker (uCTX-II) by ~19–30% after 1 year and strongly suppressed bone resorption marker (uCTX-I), suggesting protective effects on cartilage and bone.

Trust comment: Randomized, double-blind, placebo-controlled trials with 171 completers and validated biochemical and BMD endpoints; robust design though longer-term clinical OA outcomes not provided.

Study Details

PMID:15542048
Participants:171
Impact:Decrease of ~70% vs placebo (P<0.0001)
Trust score:4/5

Bone mineral density (spine and hip)

1 evidences

Oral and transdermal postmenopausal estrogen therapy decreased a urine cartilage-degradation marker (uCTX-II) by ~19–30% after 1 year and strongly suppressed bone resorption marker (uCTX-I), suggesting protective effects on cartilage and bone.

Trust comment: Randomized, double-blind, placebo-controlled trials with 171 completers and validated biochemical and BMD endpoints; robust design though longer-term clinical OA outcomes not provided.

Study Details

PMID:15542048
Participants:171
Impact:Consistent with marker changes: spine +7–8% and hip +4–6% over 2 years (reported association)
Trust score:4/5

Ridge width (mesial/midfacial/distal)

1 evidences

Using deproteinized bovine bone with 10% collagen plus collagen membrane (test) after molar/premolar extraction preserved ridge width and vertical bone better than natural healing at 4 months.

Trust comment: Randomized controlled trial directly testing collagen-containing graft/membrane with objective 3D measures, but small sample (n=31).

Study Details

PMID:38198438
Participants:31
Impact:Test group showed ~25% greater ridge width gain versus control (significant)
Trust score:4/5

Vertical bone reduction

1 evidences

Using deproteinized bovine bone with 10% collagen plus collagen membrane (test) after molar/premolar extraction preserved ridge width and vertical bone better than natural healing at 4 months.

Trust comment: Randomized controlled trial directly testing collagen-containing graft/membrane with objective 3D measures, but small sample (n=31).

Study Details

PMID:38198438
Participants:31
Impact:Test group had significantly less vertical ridge reduction than control (P < 0.05)
Trust score:4/5

Volumetric crestal bone maintenance

1 evidences

Using deproteinized bovine bone with 10% collagen plus collagen membrane (test) after molar/premolar extraction preserved ridge width and vertical bone better than natural healing at 4 months.

Trust comment: Randomized controlled trial directly testing collagen-containing graft/membrane with objective 3D measures, but small sample (n=31).

Study Details

PMID:38198438
Participants:31
Impact:ARR with DBBM-C + collagen membrane maintained/augmented crestal bone more effectively than natural healing at 4 months
Trust score:4/5

Buccal bone thickness (RES vs N-RES)

1 evidences

At 6 months, resorbable collagen membranes showed greater buccal bone loss (~0.8 mm) but an accompanying soft tissue thickness gain (~+0.6 mm) compared with non-resorbable membranes (bone ~0.1 mm loss, soft tissue ~0.0 mm).

Trust comment: Randomized controlled trial directly comparing collagen (resorbable) versus non-resorbable membranes with quantitative CBCT/STL outcomes, but limited sample (14–25 evaluable datasets) and short follow-up.

Study Details

PMID:40199760
Participants:25
Impact:RES group mean reduction ≈ 0.8 mm; N-RES ≈ 0.1 mm (intergroup P = 0.017; several level-specific P ≤ 0.006)
Trust score:4/5

Buccal soft tissue thickness

1 evidences

At 6 months, resorbable collagen membranes showed greater buccal bone loss (~0.8 mm) but an accompanying soft tissue thickness gain (~+0.6 mm) compared with non-resorbable membranes (bone ~0.1 mm loss, soft tissue ~0.0 mm).

Trust comment: Randomized controlled trial directly comparing collagen (resorbable) versus non-resorbable membranes with quantitative CBCT/STL outcomes, but limited sample (14–25 evaluable datasets) and short follow-up.

Study Details

PMID:40199760
Participants:25
Impact:RES group gain ≈ +0.6 mm (intragroup P=0.125); N-RES ~0.0 mm (no change); trend for greater soft tissue gain with RES (intergroup P≈0.097)
Trust score:4/5

Outer contour loss

1 evidences

At 6 months, resorbable collagen membranes showed greater buccal bone loss (~0.8 mm) but an accompanying soft tissue thickness gain (~+0.6 mm) compared with non-resorbable membranes (bone ~0.1 mm loss, soft tissue ~0.0 mm).

Trust comment: Randomized controlled trial directly comparing collagen (resorbable) versus non-resorbable membranes with quantitative CBCT/STL outcomes, but limited sample (14–25 evaluable datasets) and short follow-up.

Study Details

PMID:40199760
Participants:25
Impact:Minor overall contour loss: RES ≈ -0.2 mm; N-RES ≈ -0.1 mm
Trust score:4/5

healing success rate

1 evidences

Small prospective study found better healing of through-and-through lesions when GTR with bovine bone plus a collagen membrane was used.

Trust comment: Prospective clinical study with small sample of teeth and short follow-up; preliminary but clinically relevant.

Study Details

PMID:18605602
Participants:31
Impact:GTR 88% vs control 57% (≈+31 percentage points)
Trust score:3/5

doubtful/failed healing

1 evidences

Small prospective study found better healing of through-and-through lesions when GTR with bovine bone plus a collagen membrane was used.

Trust comment: Prospective clinical study with small sample of teeth and short follow-up; preliminary but clinically relevant.

Study Details

PMID:18605602
Participants:31
Impact:6 doubtful, 2 failures among 31 evaluated (overall 71% success across cohort)
Trust score:3/5

bone fill

1 evidences

Randomized trial in periodontitis patients showed similar pocket depth and attachment gains for both barriers but greater bone fill with the collagen membrane at 6 months.

Trust comment: Randomized clinical trial but small sample (30) and short-term follow-up; results plausible and directly measured.

Study Details

PMID:20228976
Participants:30
Impact:+2.57 mm (collagen) vs +0.33 mm (PLA); collagen > PLA at 6 months
Trust score:3/5

proximal femur BMD

1 evidences

In elderly sedentary men, recreational football increased proximal femur BMD and markers of bone formation and turnover over 12 months.

Trust comment: Randomized small trial with objective BMD and biochemical measures but limited by small group sizes (n≈9 per arm).

Study Details

PMID:24903207
Participants:26
Impact:+5.4% (0 to 12 months) in football group
Trust score:3/5

CTX-1 (bone resorption marker)

2 evidences

In elderly sedentary men, recreational football increased proximal femur BMD and markers of bone formation and turnover over 12 months.

Trust comment: Randomized small trial with objective BMD and biochemical measures but limited by small group sizes (n≈9 per arm).

Study Details

PMID:24903207
Participants:26
Impact:+43% main effect after 12 months in football group
Trust score:3/5

Single 1000 mg calcium dose from milk or calcium carbonate acutely reduced bone resorption (CTX-1) and lowered PTH in postmenopausal women regardless of visceral fat.

Trust comment: Randomized three-period crossover in 77 postmenopausal women with frequent timed sampling; robust design for acute effects.

Study Details

PMID:36967157
Participants:77
Impact:-44% with milk or calcium carbonate; -18% with juice
Trust score:4/5

pain score improvement

1 evidences

Randomized study in metastatic bone disease showed greater symptomatic pain improvement and suppression of biochemical bone resorption with IV pamidronate versus oral clodronate.

Trust comment: Randomized comparative study with objective biochemical markers and clinically meaningful symptomatic outcomes; moderate sample size.

Study Details

PMID:11762816
Participants:51
Impact:9/16 improved with pamidronate vs 4/16 and 2/11 in other arms; significant (P<0.01 at 3 months)
Trust score:4/5

urinary collagen crosslinks (bone resorption)

1 evidences

Randomized study in metastatic bone disease showed greater symptomatic pain improvement and suppression of biochemical bone resorption with IV pamidronate versus oral clodronate.

Trust comment: Randomized comparative study with objective biochemical markers and clinically meaningful symptomatic outcomes; moderate sample size.

Study Details

PMID:11762816
Participants:51
Impact:decrease correlated with pain improvement (P=0.01)
Trust score:4/5

P1NP (procollagen type I N‑propeptide)

1 evidences

Infliximab induction increased markers of bone formation and resorption in children with Crohn's disease and these changes associated with improved growth and disease activity.

Trust comment: Well-characterized multicenter pediatric trial with objective biomarker and growth outcomes, though specific effect sizes for some markers are not provided here.

Study Details

PMID:19081527
Participants:112
Impact:Increased during induction (P < .001); improvement associated with increased height z-score and decreased PCDAI
Trust score:4/5

Relative attachment level

1 evidences

Split-mouth randomized study in 40 patients comparing scaling/root planing alone versus adjunctive collagen-based tetracycline fibers for chronic periodontitis over 3 months.

Trust comment: Direct clinical use of a collagen-based delivery matrix in humans with a randomized split-mouth design; moderate quality but short follow-up and adjunctive antibiotic confounds collagen-specific effects.

Study Details

PMID:25044345
Participants:40
Impact:Greater attachment gain with adjunctive collagen-tetracycline fibers vs control over 3 months
Trust score:3/5

ACR-20 response rate

1 evidences

Oral chicken type II collagen (0.1 mg/day) reduced pain, stiffness and joint counts in RA patients but was less effective than methotrexate and had fewer/milder side effects.

Trust comment: Large multicenter randomized double-blind phase III trial with active comparator (MTX); good design though NSAID co-therapy and some dropouts limit interpretation.

Study Details

PMID:19951408
Participants:454
Impact:CCII 41.6% responders at 24 weeks (ACR-20); lower than MTX 57.9% (24 weeks)
Trust score:4/5

Morning stiffness (minutes)

1 evidences

Oral chicken type II collagen (0.1 mg/day) reduced pain, stiffness and joint counts in RA patients but was less effective than methotrexate and had fewer/milder side effects.

Trust comment: Large multicenter randomized double-blind phase III trial with active comparator (MTX); good design though NSAID co-therapy and some dropouts limit interpretation.

Study Details

PMID:19951408
Participants:454
Impact:Decreased from 99.26 min to 36.12 min at 24 weeks (−63.6% absolute change)
Trust score:4/5

WOMAC pain score

1 evidences

Adding native/hydrolyzed collagen to a combo of CS/GL/MSM/HA produced larger pain reductions and better function than the same regimen without collagen in knee OA exacerbations.

Trust comment: Randomized single-center phase IV study with small sample size providing positive signals but limited generalizability.

Study Details

PMID:40561485
Participants:60
Impact:Reduced −76% with collagen vs −47% without (p=0.04)
Trust score:3/5

Function (walking speed / Timed Up-and-Go)

1 evidences

Adding native/hydrolyzed collagen to a combo of CS/GL/MSM/HA produced larger pain reductions and better function than the same regimen without collagen in knee OA exacerbations.

Trust comment: Randomized single-center phase IV study with small sample size providing positive signals but limited generalizability.

Study Details

PMID:40561485
Participants:60
Impact:Walking speed +12%; Timed Up-and-Go time −42% (both p<0.05)
Trust score:3/5

Alveolar bone (CADIA) increase

1 evidences

Use of a dual anti-collagen membrane for guided tissue regeneration produced greater 1-year clinical attachment gains and bone density increases than an atelocollagen membrane; results were stable to 6 years.

Trust comment: Randomized clinical trial but very small number of patients/teeth limits external validity despite long-term follow-up.

Study Details

PMID:21163010
Participants:24
Impact:CADIA +53.14 ± 21.35 (dual) vs +32.96 ± 17.97 (atelocollagen) at 1 year (P=0.031)
Trust score:3/5

Long-term stability

1 evidences

Use of a dual anti-collagen membrane for guided tissue regeneration produced greater 1-year clinical attachment gains and bone density increases than an atelocollagen membrane; results were stable to 6 years.

Trust comment: Randomized clinical trial but very small number of patients/teeth limits external validity despite long-term follow-up.

Study Details

PMID:21163010
Participants:24
Impact:Clinical parameters remained essentially stable at 3 and 6 years compared to 1 year
Trust score:3/5

Anterior chamber flare (laser flare photometry)

1 evidences

Deep sclerectomy with a collagen implant produced lower early post-operative anterior chamber inflammation than standard trabeculectomy, with significant differences up to 1 month.

Trust comment: Prospective randomized study with objective inflammatory measurements but modest sample size.

Study Details

PMID:9717655
Participants:46
Impact:Day 1: 16.3 ± 7.8 (DSCI) vs 72.5 ± 38.9 (trabeculectomy); Week 1: 7.8 ± 4.6 vs 44.7 ± 29.2; Month 1: 5.9 ± 1.6 vs 7.0 ± 2.8 (P≤0.012 for reported timepoints)
Trust score:4/5

Post-operative inflammation duration

1 evidences

Deep sclerectomy with a collagen implant produced lower early post-operative anterior chamber inflammation than standard trabeculectomy, with significant differences up to 1 month.

Trust comment: Prospective randomized study with objective inflammatory measurements but modest sample size.

Study Details

PMID:9717655
Participants:46
Impact:Lower inflammation with collagen implant significant through 1 month, similar thereafter
Trust score:4/5

Relative vertical bone fill

1 evidences

A native collagen membrane produced similar vertical bone fill and soft-tissue outcomes to a synthetic PEG membrane at 6 months and 18 months; differences were not statistically significant and non-inferiority was not conclusively demonstrated.

Trust comment: Prospective randomized multicenter trial with adequate sample size; results show comparable performance though non-inferiority margin not met.

Study Details

PMID:32875638
Participants:117
Impact:PEG 59.7% vs collagen membrane 64.4% (no statistically significant difference)
Trust score:4/5

Absolute defect reduction

1 evidences

A native collagen membrane produced similar vertical bone fill and soft-tissue outcomes to a synthetic PEG membrane at 6 months and 18 months; differences were not statistically significant and non-inferiority was not conclusively demonstrated.

Trust comment: Prospective randomized multicenter trial with adequate sample size; results show comparable performance though non-inferiority margin not met.

Study Details

PMID:32875638
Participants:117
Impact:Mean reduction 2.5 mm (PEG) vs 3.2 mm (collagen) at 6 months (both significant vs baseline; between-group NS)
Trust score:4/5

Marginal bone level / soft tissue outcomes

1 evidences

A native collagen membrane produced similar vertical bone fill and soft-tissue outcomes to a synthetic PEG membrane at 6 months and 18 months; differences were not statistically significant and non-inferiority was not conclusively demonstrated.

Trust comment: Prospective randomized multicenter trial with adequate sample size; results show comparable performance though non-inferiority margin not met.

Study Details

PMID:32875638
Participants:117
Impact:MBL increase and soft tissue complications similar between groups up to 18 months
Trust score:4/5

Collagen-induced platelet aggregation (EC50)

1 evidences

In vitro and two randomized healthy-volunteer trials showed near-complete Lp-PLA2 inhibition but no clinically relevant enhancement of platelet aggregation to collagen, ADP, or PAF.

Trust comment: Well-powered, randomized double-blind clinical trials with objective aggregation assays and consistent in vitro corroboration.

Study Details

PMID:24475026
Participants:87
Impact:no significant change; EC50 ratio rilapladib:placebo day14 1.10 (95% CI 0.98–1.23), day35 1.06 (95% CI 0.94–1.20)
Trust score:5/5

Pain (WOMAC Pain)

1 evidences

Randomized double-blind placebo-controlled trial (8 weeks) in 32 patients with grade 1–2 meniscal tears; multi-ingredient product containing type I/III and type II collagen (plus glucosamine, chondroitin, hyaluronic acid, vitamin C) improved pain and several quality-of-life and function scores versus placebo.

Trust comment: Randomized, double-blind, placebo-controlled design but small sample (n=32) and the product contained multiple active ingredients, limiting attribution solely to collagen.

Study Details

PMID:39755603
Participants:32
Impact:-5.4 points (from 7.6 to 2.2; collagen group pre→post)
Trust score:3/5

Quality of life (SF-12 PCS)

1 evidences

Randomized double-blind placebo-controlled trial (8 weeks) in 32 patients with grade 1–2 meniscal tears; multi-ingredient product containing type I/III and type II collagen (plus glucosamine, chondroitin, hyaluronic acid, vitamin C) improved pain and several quality-of-life and function scores versus placebo.

Trust comment: Randomized, double-blind, placebo-controlled design but small sample (n=32) and the product contained multiple active ingredients, limiting attribution solely to collagen.

Study Details

PMID:39755603
Participants:32
Impact:+14.1 points (from 38.3 to 52.4; collagen group pre→post)
Trust score:3/5

Physical function (LEFS)

1 evidences

Randomized double-blind placebo-controlled trial (8 weeks) in 32 patients with grade 1–2 meniscal tears; multi-ingredient product containing type I/III and type II collagen (plus glucosamine, chondroitin, hyaluronic acid, vitamin C) improved pain and several quality-of-life and function scores versus placebo.

Trust comment: Randomized, double-blind, placebo-controlled design but small sample (n=32) and the product contained multiple active ingredients, limiting attribution solely to collagen.

Study Details

PMID:39755603
Participants:32
Impact:+22.9 points (from 45.6 to 68.5; collagen group pre→post)
Trust score:3/5

Plasma vitamin B12

1 evidences

Randomized 1-year nutrition intervention in older adults comparing twice-daily sachets of whey, collagen hydrolysate, or carbohydrate; collagen supplementation (1.3 µg B12/day) did not change plasma B12, holoTC, or MMA after 12 months compared with baseline.

Trust comment: Large, randomized controlled trial with objective biomarker measurements and reasonable follow-up, though collagen sachet delivered lower B12 than whey and efficacy pertains to B12 biomarkers rather than other collagen effects.

Study Details

PMID:32645934
Participants:110
Impact:no change after 12 months in collagen group (baseline vs 12 mo)
Trust score:4/5

Holotranscobalamin (holoTC)

1 evidences

Randomized 1-year nutrition intervention in older adults comparing twice-daily sachets of whey, collagen hydrolysate, or carbohydrate; collagen supplementation (1.3 µg B12/day) did not change plasma B12, holoTC, or MMA after 12 months compared with baseline.

Trust comment: Large, randomized controlled trial with objective biomarker measurements and reasonable follow-up, though collagen sachet delivered lower B12 than whey and efficacy pertains to B12 biomarkers rather than other collagen effects.

Study Details

PMID:32645934
Participants:110
Impact:no change after 12 months in collagen group
Trust score:4/5

Methylmalonic acid (MMA)

1 evidences

Randomized 1-year nutrition intervention in older adults comparing twice-daily sachets of whey, collagen hydrolysate, or carbohydrate; collagen supplementation (1.3 µg B12/day) did not change plasma B12, holoTC, or MMA after 12 months compared with baseline.

Trust comment: Large, randomized controlled trial with objective biomarker measurements and reasonable follow-up, though collagen sachet delivered lower B12 than whey and efficacy pertains to B12 biomarkers rather than other collagen effects.

Study Details

PMID:32645934
Participants:110
Impact:no overall change at 12 mo (6 mo vs 18 mo showed a decline in MMA for COLL group P=0.008 but no sustained 12-mo effect)
Trust score:4/5

30-day major bleeding

1 evidences

In PCI patients, using a collagen plug vascular closure device did not change the reduction in major bleeding seen with bivalirudin versus heparin+abciximab.

Trust comment: Large randomized trial dataset with a predefined bleeding endpoint; VCD use was nonrandomized but analysis is robust and sample size is large.

Study Details

PMID:24118114
Participants:1711
Impact:UFH+abciximab 4.8% vs bivalirudin 2.3% with collagen VCD; 4.6% vs 2.7% without VCD (absolute reductions ~2.5% and ~1.9%)
Trust score:4/5

interaction between collagen VCD use and randomized treatment

1 evidences

In PCI patients, using a collagen plug vascular closure device did not change the reduction in major bleeding seen with bivalirudin versus heparin+abciximab.

Trust comment: Large randomized trial dataset with a predefined bleeding endpoint; VCD use was nonrandomized but analysis is robust and sample size is large.

Study Details

PMID:24118114
Participants:1711
Impact:no interaction (Pint = 0.76)
Trust score:4/5

device performance success

1 evidences

A collagen corneal shield gave worse device performance and more adverse events than a hydrogel bandage, while pain scores were similar.

Trust comment: Prospective randomized multicenter single‑masked trial with clear endpoints and substantial sample size, directly testing a collagen device.

Study Details

PMID:21183106
Participants:420
Impact:collagen shield 26.5% vs hydrogel bandage 78.6% (difference −52.1%)
Trust score:4/5

maximum postoperative pain (first 4 h)

1 evidences

A collagen corneal shield gave worse device performance and more adverse events than a hydrogel bandage, while pain scores were similar.

Trust comment: Prospective randomized multicenter single‑masked trial with clear endpoints and substantial sample size, directly testing a collagen device.

Study Details

PMID:21183106
Participants:420
Impact:collagen shield mean 1.1 vs hydrogel 1.3 (noninferior)
Trust score:4/5

vital bone fill

1 evidences

Compared two graft materials after tooth extraction; putty allograft produced more new vital bone than bovine xenograft.

Trust comment: Randomized, controlled, blinded human clinical study but small sample (n=24), so moderate-high trust.

Study Details

PMID:15346745
Participants:24
Impact:+~35 percentage points (61% vs 26%)
Trust score:4/5

ridge width

1 evidences

Compared two graft materials after tooth extraction; putty allograft produced more new vital bone than bovine xenograft.

Trust comment: Randomized, controlled, blinded human clinical study but small sample (n=24), so moderate-high trust.

Study Details

PMID:15346745
Participants:24
Impact:-0.50 mm (both groups)
Trust score:4/5

wound size (day 7)

1 evidences

Topical estrogen patches improved wound healing in elderly subjects, increasing collagen and wound strength and reducing inflammation.

Trust comment: Double-blind randomized human trial with clear outcomes though modest sample size (n=36).

Study Details

PMID:10514397
Participants:36
Impact:decreased (improved healing at day 7)
Trust score:4/5

collagen levels

1 evidences

Topical estrogen patches improved wound healing in elderly subjects, increasing collagen and wound strength and reducing inflammation.

Trust comment: Double-blind randomized human trial with clear outcomes though modest sample size (n=36).

Study Details

PMID:10514397
Participants:36
Impact:increased (days 7 and 80)
Trust score:4/5

wound strength (day 80)

1 evidences

Topical estrogen patches improved wound healing in elderly subjects, increasing collagen and wound strength and reducing inflammation.

Trust comment: Double-blind randomized human trial with clear outcomes though modest sample size (n=36).

Study Details

PMID:10514397
Participants:36
Impact:increased
Trust score:4/5

collagen organization (collagen III/I ratio)

1 evidences

Composite graft using acellular dermal matrix plus thin split-thickness skin improved skin organization, functional scores, and reduced scarring versus skin alone.

Trust comment: Comparative clinical study with reasonable sample (n=60) but retrospective design limits strength.

Study Details

PMID:25687834
Participants:60
Impact:lower collagen III/I ratio in ADM group vs control
Trust score:3/5

Vancouver Burn Skin Score (VBSS)

1 evidences

Composite graft using acellular dermal matrix plus thin split-thickness skin improved skin organization, functional scores, and reduced scarring versus skin alone.

Trust comment: Comparative clinical study with reasonable sample (n=60) but retrospective design limits strength.

Study Details

PMID:25687834
Participants:60
Impact:improved (significant difference, P<0.001)
Trust score:3/5

functional recovery (Barthel Index)

1 evidences

Composite graft using acellular dermal matrix plus thin split-thickness skin improved skin organization, functional scores, and reduced scarring versus skin alone.

Trust comment: Comparative clinical study with reasonable sample (n=60) but retrospective design limits strength.

Study Details

PMID:25687834
Participants:60
Impact:improved (P=0.005)
Trust score:3/5

clinical cure (test-of-cure)

1 evidences

Adding a gentamicin-collagen sponge to standard care increased clinical cure and pathogen eradication rates in moderately infected diabetic foot ulcers.

Trust comment: Randomized multicenter pilot RCT in humans with clear clinical and microbiological endpoints though sample is modest.

Study Details

PMID:22659765
Participants:56
Impact:+30 percentage points (100% [22/22] vs 70% [7/10])
Trust score:4/5

pathogen eradication rate

1 evidences

Adding a gentamicin-collagen sponge to standard care increased clinical cure and pathogen eradication rates in moderately infected diabetic foot ulcers.

Trust comment: Randomized multicenter pilot RCT in humans with clear clinical and microbiological endpoints though sample is modest.

Study Details

PMID:22659765
Participants:56
Impact:increased (higher at all visits; P ≤ .038)
Trust score:4/5

time to pathogen eradication

1 evidences

Adding a gentamicin-collagen sponge to standard care increased clinical cure and pathogen eradication rates in moderately infected diabetic foot ulcers.

Trust comment: Randomized multicenter pilot RCT in humans with clear clinical and microbiological endpoints though sample is modest.

Study Details

PMID:22659765
Participants:56
Impact:reduced (P < .001)
Trust score:4/5

Frey's syndrome incidence

1 evidences

Implanting acellular dermal matrix at parotidectomy reduced postoperative depressed deformities and markedly reduced Frey's syndrome compared with controls.

Trust comment: Comparative case series with moderate sample size but likely non-randomized and observational, limiting causal inference.

Study Details

PMID:22769423
Participants:70
Impact:-30.7 percentage points (3.4% vs 34.1%)
Trust score:3/5

infra-auricular depressed deformity

1 evidences

Implanting acellular dermal matrix at parotidectomy reduced postoperative depressed deformities and markedly reduced Frey's syndrome compared with controls.

Trust comment: Comparative case series with moderate sample size but likely non-randomized and observational, limiting causal inference.

Study Details

PMID:22769423
Participants:70
Impact:reduced (improved facial contour and symmetry)
Trust score:3/5

Plasma tryptophan concentration

1 evidences

29 healthy volunteers received gelatin-based collagen peptide mixtures (with or without Trp); CP-Trp lowered plasma tryptophan, CP+Trp produced a large increase in plasma tryptophan; no other significant effects on mood or cortisol.

Trust comment: Randomized double-blind (one crossover) biochemical study with clear plasma amino-acid outcomes but small sample and limited clinical (mood/cortisol) effects.

Study Details

PMID:26655163
Participants:29
Impact:CP-Trp: decreased (efficiently); CP+Trp: large significant increase
Trust score:4/5

Mood

1 evidences

29 healthy volunteers received gelatin-based collagen peptide mixtures (with or without Trp); CP-Trp lowered plasma tryptophan, CP+Trp produced a large increase in plasma tryptophan; no other significant effects on mood or cortisol.

Trust comment: Randomized double-blind (one crossover) biochemical study with clear plasma amino-acid outcomes but small sample and limited clinical (mood/cortisol) effects.

Study Details

PMID:26655163
Participants:29
Impact:no significant change between CP-Trp and CP+Trp
Trust score:4/5

cortisol

1 evidences

29 healthy volunteers received gelatin-based collagen peptide mixtures (with or without Trp); CP-Trp lowered plasma tryptophan, CP+Trp produced a large increase in plasma tryptophan; no other significant effects on mood or cortisol.

Trust comment: Randomized double-blind (one crossover) biochemical study with clear plasma amino-acid outcomes but small sample and limited clinical (mood/cortisol) effects.

Study Details

PMID:26655163
Participants:29
Impact:no significant change reported
Trust score:4/5

vertical probing depth reduction

1 evidences

Use of a bovine bone graft plus a bioabsorbable collagen barrier led to greater soft- and hard-tissue improvement than open-flap debridement over the study period.

Trust comment: Small clinical study with direct human data and clear measurements but limited sample size (21 patients) and unclear randomisation details.

Study Details

PMID:11829390
Participants:21
Impact:+2.0 mm (BO/BG) vs +0.3 mm (OFD)
Trust score:3/5

horizontal probing depth reduction

1 evidences

Use of a bovine bone graft plus a bioabsorbable collagen barrier led to greater soft- and hard-tissue improvement than open-flap debridement over the study period.

Trust comment: Small clinical study with direct human data and clear measurements but limited sample size (21 patients) and unclear randomisation details.

Study Details

PMID:11829390
Participants:21
Impact:+2.2 mm (BO/BG) vs +0.2 mm (OFD)
Trust score:3/5

new bone formation (overall)

1 evidences

Extraction sockets grafted with Bio-Oss Collagen showed less new bone formation at 12 weeks than ungrafted sockets.

Trust comment: Prospective, randomized socket allocation with histologic endpoints but modest sample size (25 patients, 39 sockets) and short 12-week follow-up.

Study Details

PMID:21483892
Participants:25
Impact:25% (grafted) vs 44% (ungrafted)
Trust score:3/5

regional bone formation difference

1 evidences

Extraction sockets grafted with Bio-Oss Collagen showed less new bone formation at 12 weeks than ungrafted sockets.

Trust comment: Prospective, randomized socket allocation with histologic endpoints but modest sample size (25 patients, 39 sockets) and short 12-week follow-up.

Study Details

PMID:21483892
Participants:25
Impact:greater formation in apical vs coronal regions (significant)
Trust score:3/5

primary 5-year graft patency

1 evidences

Randomized multicenter trial comparing collagen-coated Dacron, gelatin-coated Dacron, and PTFE grafts in abdominal aortic bifurcation surgery; long-term patency similar but infections occurred only with Dacron grafts.

Trust comment: Large randomized multicenter trial with long follow-up and clear outcomes, though infections pooled across Dacron grafts limit attribution to collagen alone.

Study Details

PMID:11562661
Participants:315
Impact:COL-D 89% (GEL-D 92%, PTFE 91%)
Trust score:4/5

secondary 5-year graft patency

1 evidences

Randomized multicenter trial comparing collagen-coated Dacron, gelatin-coated Dacron, and PTFE grafts in abdominal aortic bifurcation surgery; long-term patency similar but infections occurred only with Dacron grafts.

Trust comment: Large randomized multicenter trial with long follow-up and clear outcomes, though infections pooled across Dacron grafts limit attribution to collagen alone.

Study Details

PMID:11562661
Participants:315
Impact:COL-D 100% (GEL-D 97%, PTFE 97%)
Trust score:4/5

graft infection rate (Dacron vs PTFE)

1 evidences

Randomized multicenter trial comparing collagen-coated Dacron, gelatin-coated Dacron, and PTFE grafts in abdominal aortic bifurcation surgery; long-term patency similar but infections occurred only with Dacron grafts.

Trust comment: Large randomized multicenter trial with long follow-up and clear outcomes, though infections pooled across Dacron grafts limit attribution to collagen alone.

Study Details

PMID:11562661
Participants:315
Impact:Dacron 3% (6/209) vs PTFE 0% (0/106)
Trust score:4/5

radiographic bone fill

2 evidences

In combined surgical therapy of peri-implantitis with bone graft and collagen membrane, the choice of debridement/decontamination method (Er:YAG laser vs curets+saline) did not significantly affect 6-month clinical or radiographic outcomes.

Trust comment: Randomized controlled clinical study on humans with objective clinical and radiographic measures, but small sample and short follow-up limit generalizability.

Study Details

PMID:21219392
Participants:30
Impact:Comparable radiographic bone fill in both groups at 6 months (no significant difference)
Trust score:4/5

Addition of deproteinized bovine bone mineral plus a collagen membrane produced greater radiographic bone fill of intrabony periodontal defects at 1 year versus flap surgery alone.

Trust comment: Multi-center randomized-controlled trial (n=120) with objective radiographic endpoints supports moderate-to-high trust in results.

Study Details

PMID:16634957
Participants:120
Impact:Test group mean fill 3.2±1.7 mm vs control 1.7±1.9 mm at 12 months (difference ≈ +1.5 mm)
Trust score:4/5

I-QOL ≥10 point improvement (moderate-severe SUI)

1 evidences

Randomized controlled trial of transurethral radiofrequency collagen micro-remodeling vs sham for female stress urinary incontinence showing improved quality-of-life scores and increased leak point pressure at 12 months.

Trust comment: Well-designed randomized controlled trial with adequate sample size and clinically relevant outcomes.

Study Details

PMID:16673379
Participants:173
Impact:74% of treated women achieved ≥10-point improvement
Trust score:4/5

leak point pressure (LPP)

1 evidences

Randomized controlled trial of transurethral radiofrequency collagen micro-remodeling vs sham for female stress urinary incontinence showing improved quality-of-life scores and increased leak point pressure at 12 months.

Trust comment: Well-designed randomized controlled trial with adequate sample size and clinically relevant outcomes.

Study Details

PMID:16673379
Participants:173
Impact:statistically significant elevation in treated vs reduction in sham (P=0.02)
Trust score:4/5

overall healing rate

1 evidences

Prospective clinical trial using anorganic bovine bone covered with a resorbable collagen membrane versus no graft/membrane in large periapical lesions; no significant benefit of the collagen membrane approach was found at one year.

Trust comment: Prospective trial with moderate sample size but outcomes reported per tooth and no demonstrated benefit for the collagen membrane intervention.

Study Details

PMID:17517295
Participants:41
Impact:46/59 teeth (78%) successful healing at 1 year
Trust score:3/5

effect of collagen membrane + graft vs control

1 evidences

Prospective clinical trial using anorganic bovine bone covered with a resorbable collagen membrane versus no graft/membrane in large periapical lesions; no significant benefit of the collagen membrane approach was found at one year.

Trust comment: Prospective trial with moderate sample size but outcomes reported per tooth and no demonstrated benefit for the collagen membrane intervention.

Study Details

PMID:17517295
Participants:41
Impact:no statistically significant difference between groups
Trust score:3/5

fluorescein staining score

1 evidences

Prospective case series testing a thermosensitive atelocollagen punctal plug with/without preheating; preheating (41°C) improved solidification and produced greater improvements in signs and symptoms of dry eye at 1 month.

Trust comment: Prospective case series with small sample and short follow-up but clear, measurable improvements particularly with preheating preparation.

Study Details

PMID:24211863
Participants:27
Impact:conventional: 3.5 → 2.5 (−1.0); preheating: 3.7 → 1.5 (−2.2)
Trust score:3/5

tear meniscometry

1 evidences

Prospective case series testing a thermosensitive atelocollagen punctal plug with/without preheating; preheating (41°C) improved solidification and produced greater improvements in signs and symptoms of dry eye at 1 month.

Trust comment: Prospective case series with small sample and short follow-up but clear, measurable improvements particularly with preheating preparation.

Study Details

PMID:24211863
Participants:27
Impact:preheating: 0.6 → 1.1 mm (+0.5 mm)
Trust score:3/5

tear film break-up time (BUT)

1 evidences

Prospective case series testing a thermosensitive atelocollagen punctal plug with/without preheating; preheating (41°C) improved solidification and produced greater improvements in signs and symptoms of dry eye at 1 month.

Trust comment: Prospective case series with small sample and short follow-up but clear, measurable improvements particularly with preheating preparation.

Study Details

PMID:24211863
Participants:27
Impact:preheating: 3.2 → 4.8 s (+1.6 s)
Trust score:3/5

symptom VAS score

1 evidences

Prospective case series testing a thermosensitive atelocollagen punctal plug with/without preheating; preheating (41°C) improved solidification and produced greater improvements in signs and symptoms of dry eye at 1 month.

Trust comment: Prospective case series with small sample and short follow-up but clear, measurable improvements particularly with preheating preparation.

Study Details

PMID:24211863
Participants:27
Impact:preheating: 6.6 → 4.1 (−2.5 points)
Trust score:3/5

Post-op swelling (day 7 change score)

1 evidences

Prospective randomized (non-blinded) trial comparing autogenous demineralized dentin matrix with bio-collagen membrane versus natural healing after lower third molar extraction; test group showed better probing depth and radiographic bone density but slightly greater early swelling.

Trust comment: Direct clinical use of a bio-collagen membrane was assessed in a randomized trial with adequate sample size though non-blinded allocation and limited reporting details reduce confidence.

Study Details

PMID:39786610
Participants:90
Impact:+1.43 points (Test 117.35 vs Control 115.92; reported p = 0.001, greater swelling in test group)
Trust score:3/5

Hepatic collagen content (morphometry)

1 evidences

A 24-week randomized phase 2 trial (n=72) found selonsertib-treated patients had higher rates of fibrosis improvement and reductions in hepatic collagen content versus simtuzumab alone.

Trust comment: Multicenter randomized phase 2 trial with blinded central histology/imaging and consistent collagen-related endpoints, but relatively small and open-label for treatment assignment.

Study Details

PMID:28892558
Participants:72
Impact:median change: −8.7% (18 mg), −8.2% (6 mg), +2.1% (simtuzumab)
Trust score:4/5

Supracrestal tissue height (STH) change

1 evidences

Single-center randomized controlled trial in patients with thin peri-implant mucosa showed that placement of an allogenic collagen scaffold at implant placement produced modest but statistically significant soft-tissue thickening versus no grafting; marginal bone loss differences were small and not significant.

Trust comment: Randomized controlled single-center trial with blinded radiographic assessment and clearly reported outcomes, but relatively small sample and some dropouts limit generalizability.

Study Details

PMID:38748295
Participants:37
Impact:+0.50 ± 0.62 mm (Test group mean increase at re-opening) vs +0.06 ± 0.16 mm (Control)
Trust score:4/5

Marginal bone loss (MBL) at 12 months

1 evidences

Single-center randomized controlled trial in patients with thin peri-implant mucosa showed that placement of an allogenic collagen scaffold at implant placement produced modest but statistically significant soft-tissue thickening versus no grafting; marginal bone loss differences were small and not significant.

Trust comment: Randomized controlled single-center trial with blinded radiographic assessment and clearly reported outcomes, but relatively small sample and some dropouts limit generalizability.

Study Details

PMID:38748295
Participants:37
Impact:Test 0.96 ± 0.56 mm vs Control 1.06 ± 0.80 mm (difference not statistically significant, p > 0.5)
Trust score:4/5

Pocket probing depth (PPD) at 12 months

1 evidences

Single-center randomized controlled trial in patients with thin peri-implant mucosa showed that placement of an allogenic collagen scaffold at implant placement produced modest but statistically significant soft-tissue thickening versus no grafting; marginal bone loss differences were small and not significant.

Trust comment: Randomized controlled single-center trial with blinded radiographic assessment and clearly reported outcomes, but relatively small sample and some dropouts limit generalizability.

Study Details

PMID:38748295
Participants:37
Impact:Test 3.3 ± 1.0 mm vs Control 3.0 ± 0.6 mm (no clear advantage)
Trust score:4/5

Defect height reduction (% DH reduction, 6 months)

1 evidences

A randomized study testing absorbable membranes (including bovine collagen membrane) during bone grafting found membranes increased bone thickness gain.

Trust comment: Randomized clinical study with objective measures but small sample and limited defects (22 patients); results moderate-quality for collagen membrane effects.

Study Details

PMID:17956570
Participants:22
Impact:BME 68.1% reduction (ADM 73.9%, control 63.6%); no significant difference among groups (P=0.686)
Trust score:3/5

Horizontal bone gain

1 evidences

A randomized study testing absorbable membranes (including bovine collagen membrane) during bone grafting found membranes increased bone thickness gain.

Trust comment: Randomized clinical study with objective measures but small sample and limited defects (22 patients); results moderate-quality for collagen membrane effects.

Study Details

PMID:17956570
Participants:22
Impact:BME 1.6 mm vs control 1.0 mm (membrane groups greater; P=0.044)
Trust score:3/5

β-CTX (β-C-telopeptide of type I collagen)

1 evidences

IV zoledronic acid after ACDF shortened time to osteogenesis, promoted fusion, lowered a collagen degradation marker (CTX) and increased lumbar spine BMD, with improved neck disability scores.

Trust comment: Randomized controlled human study with objective biochemical and BMD outcomes but moderate single-center sample size.

Study Details

PMID:31079567
Participants:43
Impact:decreased in ZA group (significant); no significant change in control
Trust score:4/5

myocardial collagen (echoreflectivity, BB)

1 evidences

Hypertensive patients with LVH were randomized to losartan or atenolol to compare effects on myocardial collagen assessed by ultrasound echoreflectivity and serum collagen markers.

Trust comment: Randomized clinical trial with moderate sample size but only a subset (106) had feasible echoreflectivity, limiting robustness of the primary imaging outcome.

Study Details

PMID:15277331
Participants:219
Impact:losartan: decreased from 114.5 to 104.3 color levels (−10.2); between-group difference −12.8 color levels (P=0.02)
Trust score:4/5

serum collagen markers (PIP, PIIIP, CITP)

1 evidences

Hypertensive patients with LVH were randomized to losartan or atenolol to compare effects on myocardial collagen assessed by ultrasound echoreflectivity and serum collagen markers.

Trust comment: Randomized clinical trial with moderate sample size but only a subset (106) had feasible echoreflectivity, limiting robustness of the primary imaging outcome.

Study Details

PMID:15277331
Participants:219
Impact:trend toward decreased collagen markers with losartan (not statistically significant)
Trust score:4/5

urinary type I collagen breakdown products

1 evidences

Postmenopausal women received varying doses of ibandronate; higher doses increased BMD and reduced biochemical markers of bone turnover including type I collagen breakdown products.

Trust comment: Randomized, double-blind controlled trial with clear biochemical and BMD endpoints, though multi-dose design complicates single-dose interpretation.

Study Details

PMID:8922653
Participants:141
Impact:decreased (−78% at 5.0 mg)
Trust score:4/5

skin wrinkling (visual and instrumental)

1 evidences

Oral low-molecular-weight collagen peptide (1 g/day) for 12 weeks improved skin hydration, reduced wrinkles, and increased elasticity in middle-aged women.

Trust comment: Randomized double-blind placebo-controlled trial with objective measures but modest sample size (53 completers) limits generalizability.

Study Details

PMID:29949889
Participants:53
Impact:improved (visual grade improvement 10.5-fold greater vs placebo at 12 weeks; instrumental R1/R3/R4 improved, p≤0.043)
Trust score:4/5

skin elasticity (R2/R5)

1 evidences

Oral low-molecular-weight collagen peptide (1 g/day) for 12 weeks improved skin hydration, reduced wrinkles, and increased elasticity in middle-aged women.

Trust comment: Randomized double-blind placebo-controlled trial with objective measures but modest sample size (53 completers) limits generalizability.

Study Details

PMID:29949889
Participants:53
Impact:increased (R5 net elasticity significantly improved vs baseline and vs placebo at 12 weeks; p≤0.027)
Trust score:4/5

incisional hernia rate at 1 year (CT)

1 evidences

Patients undergoing VRAM flap reconstruction were randomized to collagen mesh-assisted closure or conventional closure; no significant reduction in incisional hernia at 1 year was found.

Trust comment: Well-designed randomized trial but small sample and non-significant primary outcome suggest limited evidence for efficacy.

Study Details

PMID:27805791
Participants:58
Impact:decreased (conventional 50% vs mesh 33%; absolute −17 percentage points; P=0.38, not significant)
Trust score:3/5

clinically detectable hernia (2 years)

1 evidences

Multicentre RCT: adding a non‑crosslinked porcine collagen biological mesh at stoma closure reduced clinically detectable hernias at 2 years.

Trust comment: Large, multicentre, patient- and assessor-masked randomized trial with robust follow-up and pre-specified outcomes; high internal validity.

Study Details

PMID:32035551
Participants:790
Impact:reduced from 20% to 12% (absolute -8 percentage points; adjusted RR 0.62, 95% CI 0.43–0.90; P=0.012)
Trust score:5/5

radiological hernia (1 year)

1 evidences

Multicentre RCT: adding a non‑crosslinked porcine collagen biological mesh at stoma closure reduced clinically detectable hernias at 2 years.

Trust comment: Large, multicentre, patient- and assessor-masked randomized trial with robust follow-up and pre-specified outcomes; high internal validity.

Study Details

PMID:32035551
Participants:790
Impact:reduced from 21% to 9% (absolute -12 percentage points; adjusted RR 0.42, 95% CI 0.26–0.69; P<0.001)
Trust score:5/5

surgical re‑intervention (2 years)

1 evidences

Multicentre RCT: adding a non‑crosslinked porcine collagen biological mesh at stoma closure reduced clinically detectable hernias at 2 years.

Trust comment: Large, multicentre, patient- and assessor-masked randomized trial with robust follow-up and pre-specified outcomes; high internal validity.

Study Details

PMID:32035551
Participants:790
Impact:no statistically significant change (16%→12%; adjusted RR 0.78; P=0.19)
Trust score:5/5

distant metastases (5‑year cumulative incidence)

1 evidences

Single‑center randomized trial: placing a gentamicin‑collagen implant in the pelvis at surgery was associated with a lower 5‑year cumulative incidence of distant metastases versus control.

Trust comment: Randomized long‑term follow‑up but single‑institution, modest sample and some unplanned subgroup analyses limit certainty.

Study Details

PMID:29656304
Participants:162
Impact:reduced from 23.5% to 8.6% (absolute -14.9 percentage points; crude rates 24.7%→11.1%; HR 2.4 favoring implant; P=0.005)
Trust score:3/5

disease‑free survival (overall)

1 evidences

Single‑center randomized trial: placing a gentamicin‑collagen implant in the pelvis at surgery was associated with a lower 5‑year cumulative incidence of distant metastases versus control.

Trust comment: Randomized long‑term follow‑up but single‑institution, modest sample and some unplanned subgroup analyses limit certainty.

Study Details

PMID:29656304
Participants:162
Impact:no significant difference (DFS HR 0.85; P=0.548)
Trust score:3/5

fracture healing without further intervention

1 evidences

Randomized trial (15 per arm): rhBMP‑2 on an absorbable collagen sponge plus allograft showed similar healing rates to autograft with less blood loss and comparable functional improvement.

Trust comment: Randomized controlled trial but small sample (n=30); results suggest noninferiority but limited precision.

Study Details

PMID:16818967
Participants:30
Impact:10/15 (autograft) vs 13/15 (rhBMP‑2/allograft) healed without further intervention
Trust score:3/5

estimated blood loss

1 evidences

Randomized trial (15 per arm): rhBMP‑2 on an absorbable collagen sponge plus allograft showed similar healing rates to autograft with less blood loss and comparable functional improvement.

Trust comment: Randomized controlled trial but small sample (n=30); results suggest noninferiority but limited precision.

Study Details

PMID:16818967
Participants:30
Impact:significantly less in rhBMP‑2/allograft group (exact value reported in full text)
Trust score:3/5

functional outcome (SMFA)

1 evidences

Randomized trial (15 per arm): rhBMP‑2 on an absorbable collagen sponge plus allograft showed similar healing rates to autograft with less blood loss and comparable functional improvement.

Trust comment: Randomized controlled trial but small sample (n=30); results suggest noninferiority but limited precision.

Study Details

PMID:16818967
Participants:30
Impact:comparable improvement between groups
Trust score:3/5

Radius bone mineral density (subgroup, high senescent burden)

1 evidences

Intermittent senolytic therapy did not reduce overall bone resorption but transiently increased a bone formation marker and showed benefit in a high-senescent-burden subgroup.

Trust comment: Phase 2 randomized controlled trial with clear endpoints and exploratory subgroup analyses; moderate sample size.

Study Details

PMID:38956196
Participants:60
Impact:+2.7% at 20 wk (P=0.004)
Trust score:4/5

Collagen I protein (vaginal muscularis)

1 evidences

Preoperative local vaginal estrogen increased vaginal wall thickness and markedly increased collagen I expression while decreasing collagen-degrading enzyme activity.

Trust comment: Randomized preoperative trial with tissue biopsies and molecular measures but small completed sample.

Study Details

PMID:24947034
Participants:26
Impact:+9-fold (P=0.012)
Trust score:4/5

Collagen 1α1 mRNA (vaginal muscularis)

1 evidences

Preoperative local vaginal estrogen increased vaginal wall thickness and markedly increased collagen I expression while decreasing collagen-degrading enzyme activity.

Trust comment: Randomized preoperative trial with tissue biopsies and molecular measures but small completed sample.

Study Details

PMID:24947034
Participants:26
Impact:+6.0-fold (P<0.05)
Trust score:4/5

MMP-9 activity (vaginal mucosa and muscularis)

1 evidences

Preoperative local vaginal estrogen increased vaginal wall thickness and markedly increased collagen I expression while decreasing collagen-degrading enzyme activity.

Trust comment: Randomized preoperative trial with tissue biopsies and molecular measures but small completed sample.

Study Details

PMID:24947034
Participants:26
Impact:Decreased ~6-fold in mucosa and ~4-fold in muscularis (P=0.02)
Trust score:4/5

Pain (patient VAS)

1 evidences

Intra-articular polymerized type I collagen injections improved pain and function in knee osteoarthritis versus placebo and were well tolerated.

Trust comment: Randomized, placebo-controlled trial with objective and patient-reported outcomes but moderate sample size.

Study Details

PMID:19397687
Participants:53
Impact:Decreased by 39.4 points (from 60.0 to 20.6) at 6 months vs baseline (~-66%) (P=0.003)
Trust score:4/5

Lequesne index (function)

1 evidences

Intra-articular polymerized type I collagen injections improved pain and function in knee osteoarthritis versus placebo and were well tolerated.

Trust comment: Randomized, placebo-controlled trial with objective and patient-reported outcomes but moderate sample size.

Study Details

PMID:19397687
Participants:53
Impact:Decreased by 6.0 points (from 13.1 to 7.1) at 6 months (~-46%) (P=0.027)
Trust score:4/5

Urinary CTX-II (cartilage collagen breakdown)

1 evidences

Intra-articular polymerized type I collagen injections improved pain and function in knee osteoarthritis versus placebo and were well tolerated.

Trust comment: Randomized, placebo-controlled trial with objective and patient-reported outcomes but moderate sample size.

Study Details

PMID:19397687
Participants:53
Impact:Placebo group showed a threefold increase; polymerized-collagen group did not show this increase
Trust score:4/5

sCTX (serum C-terminal telopeptide of type I collagen)

1 evidences

Greater early decreases in serum CTx were associated with larger lumbar spine BMD increases at 12 months in postmenopausal women on monthly ibandronate.

Trust comment: Large cohort from a clinical trial with biomarker–outcome association analysis; post hoc analysis limits causal claims.

Study Details

PMID:20347369
Participants:323
Impact:Larger percent decreases at 3 mo associated with higher likelihood of 12-mo BMD response (correlation with 12-mo LS BMD: r=-0.19, P=0.0016)
Trust score:4/5

Lumbar spine BMD (12 mo)

1 evidences

Greater early decreases in serum CTx were associated with larger lumbar spine BMD increases at 12 months in postmenopausal women on monthly ibandronate.

Trust comment: Large cohort from a clinical trial with biomarker–outcome association analysis; post hoc analysis limits causal claims.

Study Details

PMID:20347369
Participants:323
Impact:Percent increase at 12 mo significantly associated with percent decrease in sCTX at 3 mo (linear model R²=0.61, P=0.0007)
Trust score:4/5

Complete wound closure (by ≤6 weeks)

1 evidences

Adding dehydrated amniotic membrane allograft to standard care increased the proportion of chronic diabetic foot ulcers completely closed by 6 weeks versus standard care alone.

Trust comment: Randomized multicenter trial but small sample and open-label design increase risk of bias.

Study Details

PMID:26978860
Participants:29
Impact:35% in DAMA+SOC vs 0% in SOC (intent-to-treat, P=0.017); per-protocol 45.5% vs 0% (P=0.0083)
Trust score:3/5

Serum P1NP (type I collagen N-terminal propeptide)

1 evidences

Twelve weeks of maximal squat strength training increased lumbar spine and hip BMD and raised a bone formation marker and strength outcomes in young women.

Trust comment: Randomized training trial with objective BMD and biochemical measures though sample size is modest.

Study Details

PMID:24736773
Participants:30
Impact:+26.2% (marker of bone formation)
Trust score:4/5

Squat 1RM (maximal strength)

1 evidences

Twelve weeks of maximal squat strength training increased lumbar spine and hip BMD and raised a bone formation marker and strength outcomes in young women.

Trust comment: Randomized training trial with objective BMD and biochemical measures though sample size is modest.

Study Details

PMID:24736773
Participants:30
Impact:+97.7%
Trust score:4/5

ridge volume resorption

1 evidences

Collagenated porcine bone graft reduced ridge volume loss and basal surface shrinkage compared with cortical porcine bone after 3 months.

Trust comment: Multicentre randomized single-blind RCT with objective volumetric measures and reported p-values but small sample (n=28).

Study Details

PMID:25727443
Participants:28
Impact:coll: 244 mm3 vs cort: 349 mm3 (coll lower by 105 mm3; P=0.014)
Trust score:4/5

basal surface reduction

1 evidences

Collagenated porcine bone graft reduced ridge volume loss and basal surface shrinkage compared with cortical porcine bone after 3 months.

Trust comment: Multicentre randomized single-blind RCT with objective volumetric measures and reported p-values but small sample (n=28).

Study Details

PMID:25727443
Participants:28
Impact:final reduction coll: 4.9 mm2 vs cort: 12.2 mm2
Trust score:4/5

superior surface reduction

1 evidences

Collagenated porcine bone graft reduced ridge volume loss and basal surface shrinkage compared with cortical porcine bone after 3 months.

Trust comment: Multicentre randomized single-blind RCT with objective volumetric measures and reported p-values but small sample (n=28).

Study Details

PMID:25727443
Participants:28
Impact:coll: 40.8 mm2 vs cort: 50.7 mm2 (difference not significant)
Trust score:4/5

graft resorption

1 evidences

Adding deproteinized bovine bone mineral and a collagen membrane around block grafts reduced graft resorption but increased complication frequency.

Trust comment: Prospective randomized controlled design with clinically relevant measures but small sample and increased complications in test arm.

Study Details

PMID:21309858
Participants:22
Impact:test (DBBM+CM) resorption 0.25 mm vs control 0.89 mm (difference 0.64 mm; P=0.03)
Trust score:3/5

final augmentation gain

1 evidences

Adding deproteinized bovine bone mineral and a collagen membrane around block grafts reduced graft resorption but increased complication frequency.

Trust comment: Prospective randomized controlled design with clinically relevant measures but small sample and increased complications in test arm.

Study Details

PMID:21309858
Participants:22
Impact:final gain at implant placement: test 3.93 mm vs control 3.67 mm
Trust score:3/5

complication frequency

1 evidences

Adding deproteinized bovine bone mineral and a collagen membrane around block grafts reduced graft resorption but increased complication frequency.

Trust comment: Prospective randomized controlled design with clinically relevant measures but small sample and increased complications in test arm.

Study Details

PMID:21309858
Participants:22
Impact:3 complications in test group vs 1 in control group
Trust score:3/5

soft tissue shrinkage (long axis)

1 evidences

Primary flap closure tended to reduce soft tissue shrinkage after alveolar ridge preservation, but differences were not statistically significant.

Trust comment: Randomized clinical trial with objective scans but small sample and outcomes reported as non-significant tendencies.

Study Details

PMID:37287387
Participants:28
Impact:PC: -4.3 ± 3.1 mm vs SC: -5.9 ± 4.4 mm (trend, p>0.05)
Trust score:3/5

profilometric tissue profile change

1 evidences

Primary flap closure tended to reduce soft tissue shrinkage after alveolar ridge preservation, but differences were not statistically significant.

Trust comment: Randomized clinical trial with objective scans but small sample and outcomes reported as non-significant tendencies.

Study Details

PMID:37287387
Participants:28
Impact:PC: -1.0 ± 0.8 mm vs SC: -1.3 ± 0.5 mm (trend, p>0.05)
Trust score:3/5

mucogingival junction (MGJ) level change

1 evidences

Primary flap closure tended to reduce soft tissue shrinkage after alveolar ridge preservation, but differences were not statistically significant.

Trust comment: Randomized clinical trial with objective scans but small sample and outcomes reported as non-significant tendencies.

Study Details

PMID:37287387
Participants:28
Impact:no significant difference between groups (p>0.05)
Trust score:3/5

Collagen I/III ratio (skin)

1 evidences

Histological study comparing collagen I/III ratios in skin and aponeurosis found much lower I/III ratios in patients with ventral hernias versus controls.

Trust comment: Moderately strong histological study with a reasonably large sample (n=141) showing consistent, significant differences in collagen ratios.

Study Details

PMID:28638011
Participants:141
Impact:Group without hernia 2.81 ± 0.52 vs hernia group 1.13 ± 0.48 (≈ −60%)
Trust score:4/5

Collagen I/III ratio (aponeurosis)

1 evidences

Histological study comparing collagen I/III ratios in skin and aponeurosis found much lower I/III ratios in patients with ventral hernias versus controls.

Trust comment: Moderately strong histological study with a reasonably large sample (n=141) showing consistent, significant differences in collagen ratios.

Study Details

PMID:28638011
Participants:141
Impact:Group without hernia 2.69 ± 0.41 vs hernia group 1.09 ± 0.21 (≈ −60%)
Trust score:4/5

Correlation skin vs aponeurosis collagen ratios

1 evidences

Histological study comparing collagen I/III ratios in skin and aponeurosis found much lower I/III ratios in patients with ventral hernias versus controls.

Trust comment: Moderately strong histological study with a reasonably large sample (n=141) showing consistent, significant differences in collagen ratios.

Study Details

PMID:28638011
Participants:141
Impact:Strong direct correlation r = +0.92
Trust score:4/5

Complete hemostasis (sternal edge)

1 evidences

Randomized trial showed a collagen-based composite plus autologous plasma produced faster and more complete hemostasis at sternal and iliac crest bone sites than standard methods.

Trust comment: Randomized controlled trial with clear clinical endpoints showing significant benefit of a collagen-based product.

Study Details

PMID:11284596
Participants:83
Impact:Experimental 83% vs Control 44% (P = .002)
Trust score:4/5

Complete hemostasis (iliac crest)

1 evidences

Randomized trial showed a collagen-based composite plus autologous plasma produced faster and more complete hemostasis at sternal and iliac crest bone sites than standard methods.

Trust comment: Randomized controlled trial with clear clinical endpoints showing significant benefit of a collagen-based product.

Study Details

PMID:11284596
Participants:83
Impact:Experimental 83% vs Control 29% (P < .05)
Trust score:4/5

Time to controlled bleeding / complete hemostasis

1 evidences

Randomized trial showed a collagen-based composite plus autologous plasma produced faster and more complete hemostasis at sternal and iliac crest bone sites than standard methods.

Trust comment: Randomized controlled trial with clear clinical endpoints showing significant benefit of a collagen-based product.

Study Details

PMID:11284596
Participants:83
Impact:Significantly shorter with experimental treatment (P < .0001 for most comparisons)
Trust score:4/5

percent wound area reduction

1 evidences

Randomized trial in chronic diabetic foot ulcers: a porcine-derived purified reconstituted bilayer matrix (ECM product) produced higher 12-week healing rates, faster healing, and much greater wound area reduction than standard collagen-alginate dressing.

Trust comment: Randomized controlled trial showing large effects for a collagen-containing ECM product, but small sample (n=40) and industry funding/COI limit confidence.

Study Details

PMID:35001559
Participants:40
Impact:+86 percentage points (96% vs 9.8% at 12 weeks)
Trust score:3/5

left ventricular mass change

1 evidences

Randomized double-blind trial testing etanercept vs placebo after heart transplant; measured LV mass and myocardial collagen deposition.

Trust comment: Randomized double-blind trial but small sample and key comparisons were non-significant or borderline, so moderate confidence.

Study Details

PMID:17713431
Participants:49
Impact:increase in both groups; etanercept 19% vs placebo 33% (P=ns)
Trust score:3/5

myocardial collagen content

1 evidences

Randomized double-blind trial testing etanercept vs placebo after heart transplant; measured LV mass and myocardial collagen deposition.

Trust comment: Randomized double-blind trial but small sample and key comparisons were non-significant or borderline, so moderate confidence.

Study Details

PMID:17713431
Participants:49
Impact:placebo +39.8%, etanercept -7.0% (placebo increase trend P<0.08; changes NS for etanercept)
Trust score:3/5

lumbar spine (L2-L4) BMD change

1 evidences

In ART‑naive HIV patients who completed follow‑up, starting antiretroviral therapy (especially PI‑containing regimens) was associated with early fat mass gain and an early drop in lumbar spine BMD; vitamin D was measured but not an intervention.

Trust comment: Prospective randomized treatment allocation but small analyzable sample (35) with missing follow-up data, so moderate confidence.

Study Details

PMID:23809140
Participants:35
Impact:overall −3% at 21 months (NNRTI −1.5%, PI −4%)
Trust score:3/5

ß-crosslaps (type I collagen degradation marker)

1 evidences

In ART‑naive HIV patients who completed follow‑up, starting antiretroviral therapy (especially PI‑containing regimens) was associated with early fat mass gain and an early drop in lumbar spine BMD; vitamin D was measured but not an intervention.

Trust comment: Prospective randomized treatment allocation but small analyzable sample (35) with missing follow-up data, so moderate confidence.

Study Details

PMID:23809140
Participants:35
Impact:+50% during follow-up
Trust score:3/5

fusion rate at 24 months

2 evidences

Randomized nonblinded multicenter pilot comparing rhBMP-2 on an absorbable collagen sponge versus autograft for single-level posterior lumbar interbody fusion.

Trust comment: Prospective randomized multicenter pilot but nonblinded and modest sample size; collagen used as carrier rather than tested as therapeutic alone.

Study Details

PMID:15363423
Participants:67
Impact:investigational 92.3% vs control 77.8% (difference not statistically significant)
Trust score:3/5

Using rhBMP-2 on an absorbable collagen sponge with interbody cages yielded higher fusion rates and less operative time and blood loss than autograft, avoiding donor-site morbidity.

Trust comment: Prospective randomized multicenter trial with objective radiographic endpoints; however collagen was used as a carrier for rhBMP-2, so effects cannot be attributed solely to collagen.

Study Details

PMID:12394656
Participants:279
Impact:higher by 5.8 percentage points (94.5% vs 88.7%)
Trust score:4/5

back pain (clinical outcome)

1 evidences

Randomized nonblinded multicenter pilot comparing rhBMP-2 on an absorbable collagen sponge versus autograft for single-level posterior lumbar interbody fusion.

Trust comment: Prospective randomized multicenter pilot but nonblinded and modest sample size; collagen used as carrier rather than tested as therapeutic alone.

Study Details

PMID:15363423
Participants:67
Impact:greater improvement in investigational group at 24 months (statistically significant)
Trust score:3/5

joint function and stiffness (WOMAC/KOOS)

1 evidences

Multicenter double-blind randomized trial (stage III knee OA subgroup) showing undenatured type II chicken collagen (NK2/Artneo) improved pain, stiffness, function and quality of life vs placebo over 180 days.

Trust comment: Multicenter double-blind randomized placebo-controlled trial but subgroup sample is small (n=50), supporting moderate-to-high confidence.

Study Details

PMID:40237733
Participants:50
Impact:improved with Artneo vs placebo (statistically significant)
Trust score:4/5

NSAID use

1 evidences

Multicenter double-blind randomized trial (stage III knee OA subgroup) showing undenatured type II chicken collagen (NK2/Artneo) improved pain, stiffness, function and quality of life vs placebo over 180 days.

Trust comment: Multicenter double-blind randomized placebo-controlled trial but subgroup sample is small (n=50), supporting moderate-to-high confidence.

Study Details

PMID:40237733
Participants:50
Impact:reduced need for NSAIDs with Artneo (statistically significant)
Trust score:4/5

mid-buccal probing depth reduction

1 evidences

Split-mouth randomized trial comparing rhPDGF-BB + beta-TCP + bioabsorbable collagen dressing versus connective tissue graft for gingival recession; both improved clinically, with some measures favoring CTG and others favoring the test.

Trust comment: Well-designed split-mouth RCT with histologic corroboration but modest sample size; reliable within its surgical context.

Study Details

PMID:19335074
Participants:30
Impact:test 1.4±0.4 mm vs control 1.8±0.1 mm (P<0.001 favoring test)
Trust score:4/5

RANKL:OPG ratio

1 evidences

In early RA, higher baseline RANKL:OPG ratio and collagen degradation markers predicted faster radiological joint damage over 11 years.

Trust comment: Prospective cohort of 155 early, untreated RA patients with long (11-year) follow-up and multivariable analyses support robustness.

Study Details

PMID:20525836
Participants:155
Impact:Higher baseline levels independently predict increased annual radiological progression (36-39% explained variance; up to 44-46% with 3-month treatment effect)
Trust score:4/5

Pain level (current and 24-h average)

1 evidences

After corneal collagen crosslinking, oral ketorolac and gabapentin provided similar pain control and similar adverse event profiles.

Trust comment: Small, randomized prospective comparative case series (n=37) with randomized assignment but limited sample size.

Study Details

PMID:31216215
Participants:37
Impact:No significant difference between ketorolac and gabapentin at any time point
Trust score:3/5

Eye symptoms and systemic adverse events

1 evidences

After corneal collagen crosslinking, oral ketorolac and gabapentin provided similar pain control and similar adverse event profiles.

Trust comment: Small, randomized prospective comparative case series (n=37) with randomized assignment but limited sample size.

Study Details

PMID:31216215
Participants:37
Impact:No significant difference between groups
Trust score:3/5

Implant failures

1 evidences

Compared immediate implant placement versus delayed placement with socket preservation using bovine bone and a resorbable collagen barrier; immediate placement had more complications but similar aesthetics and patient satisfaction.

Trust comment: Pragmatic multicentre RCT with blinded assessors and complete 4-month follow-up, moderate sample size and clinically relevant endpoints.

Study Details

PMID:22282730
Participants:106
Impact:Immediate group 4% (2/54) vs delayed 0% (0/52)
Trust score:4/5

Type I collagen synthesis

1 evidences

PCA increased type I collagen synthesis in vitro and, in a 8-week lotion trial in women, significantly reduced facial wrinkle measures.

Trust comment: Placebo-controlled human skin trial with objective in vitro and ex vivo measures; small sample but direct collagen-related outcomes.

Study Details

PMID:31389672
Participants:22
Impact:increased (in vitro procollagen I induction)
Trust score:3/5

Hyaluronic acid (HA)

2 evidences

In 81 hepatitis B patients randomized to Kangxian Baogan Decoction or standard care, the decoction group showed reductions in serum fibrosis markers and improved liver pathology.

Trust comment: Randomized clinical study with biopsy and multiple biomarker outcomes, but limited methodological detail in abstract and traditional decoction limits certainty.

Study Details

PMID:12584827
Participants:81
Impact:reduced after KXBGD treatment
Trust score:3/5

Adding Clostridium butyricum to rosuvastatin in NAFLD patients improved gut microbiota composition and reduced lipids, liver enzymes, fibrosis markers and inflammatory cytokines compared with rosuvastatin alone.

Trust comment: Randomized study in 96 patients reporting multiple biomarker improvements but limited methodological detail and potential bias risk.

Study Details

PMID:35869734
Participants:96
Impact:decreased vs control (p<0.05)
Trust score:3/5

Plaque collagen content

1 evidences

Simvastatin reduced plaque inflammation and MMP activity and increased plaque collagen content, consistent with plaque stabilization.

Trust comment: Randomized pre-surgical intervention with clear, highly significant tissue-level changes supports reliability though single-center pathology measures limit generalizability.

Study Details

PMID:12654603
Participants:70
Impact:increased (P<0.0001)
Trust score:4/5

Early reoperation for bleeding

1 evidences

In cardiac surgery patients, adding collagen–gentamicin sponges to standard prophylaxis halved sternal wound infection rates (4.3% vs 9.0%) but increased early reoperation for bleeding.

Trust comment: Large randomized double-blind trial using collagen-based local sponge as antibiotic carrier with clear reduction in infections but increased bleeding risk.

Study Details

PMID:15620935
Participants:1950
Impact:Increased to 4.0% (treatment) vs 2.3% (control); p = 0.03
Trust score:4/5

Postoperative renal function

1 evidences

In cardiac surgery patients, adding collagen–gentamicin sponges to standard prophylaxis halved sternal wound infection rates (4.3% vs 9.0%) but increased early reoperation for bleeding.

Trust comment: Large randomized double-blind trial using collagen-based local sponge as antibiotic carrier with clear reduction in infections but increased bleeding risk.

Study Details

PMID:15620935
Participants:1950
Impact:No difference between groups
Trust score:4/5

Urinary CTX-II (cartilage degradation marker)

1 evidences

Two randomized treatment groups of postmenopausal women showed that certain bisphosphonate doses halved a urine cartilage collagen degradation marker (CTX-II) and markedly lowered a bone collagen marker (CTX-I).

Trust comment: Randomized long-duration clinical treatments with sizable groups and consistent marker responses, though compound/dose-specific effects noted.

Study Details

PMID:12006327
Participants:182
Impact:decreased to ≈50% of baseline with high-dose alendronate and with 2.5–5 mg ibandronate
Trust score:4/5

Serum CTX-I (bone resorption marker)

1 evidences

Two randomized treatment groups of postmenopausal women showed that certain bisphosphonate doses halved a urine cartilage collagen degradation marker (CTX-II) and markedly lowered a bone collagen marker (CTX-I).

Trust comment: Randomized long-duration clinical treatments with sizable groups and consistent marker responses, though compound/dose-specific effects noted.

Study Details

PMID:12006327
Participants:182
Impact:decreased to ≈30% of baseline within 3 months
Trust score:4/5

Fracture incidence (vertebral/nonvertebral)

1 evidences

Teriparatide substantially reduced fracture incidence versus placebo across subgroups defined by bone turnover markers.

Trust comment: Large randomized Fracture Prevention Trial with clear clinical endpoints and subgroup biomarker analyses, high-quality evidence.

Study Details

PMID:16563890
Participants:771
Impact:PINP subset: placebo 17.7% vs teriparatide 5.5%; 4-BTM subset: placebo 14.3% vs teriparatide 5.8%
Trust score:5/5

Pericellular adipose tissue fibrosis

1 evidences

In patients with type 2 diabetes, eplerenone reduced adipose tissue fibrosis and lowered collagen I/VI production compared with placebo.

Trust comment: Prespecified randomized substudy with direct tissue measures but small sample (n=30) limits generalizability.

Study Details

PMID:33055188
Participants:30
Impact:reduced with eplerenone vs placebo
Trust score:3/5

Collagen I and VI synthesis

1 evidences

In patients with type 2 diabetes, eplerenone reduced adipose tissue fibrosis and lowered collagen I/VI production compared with placebo.

Trust comment: Prespecified randomized substudy with direct tissue measures but small sample (n=30) limits generalizability.

Study Details

PMID:33055188
Participants:30
Impact:decreased with eplerenone compared with placebo
Trust score:3/5

Interstitial plaque collagen content

1 evidences

In patients with severe carotid stenosis, Qingre Quyu Granule plus standard care increased plaque collagen and reduced inflammatory and matrix-degrading markers versus control.

Trust comment: Randomized 96-patient study with histological endpoints showing consistent changes but limited by single-center scope and potential adjunct-treatment effects.

Study Details

PMID:25776840
Participants:96
Impact:increased in QQG group vs control (P<0.01)
Trust score:3/5

Tenascin-C expression

1 evidences

In patients with severe carotid stenosis, Qingre Quyu Granule plus standard care increased plaque collagen and reduced inflammatory and matrix-degrading markers versus control.

Trust comment: Randomized 96-patient study with histological endpoints showing consistent changes but limited by single-center scope and potential adjunct-treatment effects.

Study Details

PMID:25776840
Participants:96
Impact:decreased in QQG group vs control (P<0.01)
Trust score:3/5

MMP-9 and inflammatory markers

1 evidences

In patients with severe carotid stenosis, Qingre Quyu Granule plus standard care increased plaque collagen and reduced inflammatory and matrix-degrading markers versus control.

Trust comment: Randomized 96-patient study with histological endpoints showing consistent changes but limited by single-center scope and potential adjunct-treatment effects.

Study Details

PMID:25776840
Participants:96
Impact:decreased in QQG group vs control (P<0.01)
Trust score:3/5

knee osteoarthritis symptoms

1 evidences

In knee OA patients, IA-HA increased urinary CTX-II while NSAID decreased it; both improved symptoms.

Trust comment: Multicenter randomized controlled study with objective biomarker measurements and n=200, though this is a predefined sub-analysis.

Study Details

PMID:35331859
Participants:200
Impact:improvement (both IA-HA and NSAID)
Trust score:4/5

free fatty acids

1 evidences

In type 2 diabetic patients, marine collagen peptides (MCPs) improved multiple metabolic/inflammatory biomarkers versus placebo over 3 months.

Trust comment: Randomized, placebo-controlled trial with multiple biomarker endpoints and adequate sample size, though clinical outcome data are limited.

Study Details

PMID:20514986
Participants:250
Impact:decrease (significant in diabetics)
Trust score:4/5

hs-CRP (inflammation)

1 evidences

In type 2 diabetic patients, marine collagen peptides (MCPs) improved multiple metabolic/inflammatory biomarkers versus placebo over 3 months.

Trust comment: Randomized, placebo-controlled trial with multiple biomarker endpoints and adequate sample size, though clinical outcome data are limited.

Study Details

PMID:20514986
Participants:250
Impact:decrease (significant in diabetics)
Trust score:4/5

adiponectin

1 evidences

In type 2 diabetic patients, marine collagen peptides (MCPs) improved multiple metabolic/inflammatory biomarkers versus placebo over 3 months.

Trust comment: Randomized, placebo-controlled trial with multiple biomarker endpoints and adequate sample size, though clinical outcome data are limited.

Study Details

PMID:20514986
Participants:250
Impact:increase (marked)
Trust score:4/5

alveolar ridge height reduction

1 evidences

Using a bovine bone graft plus absorbable collagen membrane preserved alveolar ridge height, width, and volume better than no treatment.

Trust comment: Clinical study with objective radiographic measures but small sample size and limited follow-up for broader outcomes.

Study Details

PMID:25148644
Participants:30
Impact:trial: 1.05 mm (3 mo), 1.54 mm (6 mo) vs control: 2.12 mm (3 mo), 3.26 mm (6 mo)
Trust score:3/5

alveolar ridge width reduction

1 evidences

Using a bovine bone graft plus absorbable collagen membrane preserved alveolar ridge height, width, and volume better than no treatment.

Trust comment: Clinical study with objective radiographic measures but small sample size and limited follow-up for broader outcomes.

Study Details

PMID:25148644
Participants:30
Impact:trial: 1.11 mm (3 mo), 1.84 mm (6 mo) vs control: 2.72 mm (3 mo), 3.56 mm (6 mo)
Trust score:3/5

bone volume reduction

1 evidences

Using a bovine bone graft plus absorbable collagen membrane preserved alveolar ridge height, width, and volume better than no treatment.

Trust comment: Clinical study with objective radiographic measures but small sample size and limited follow-up for broader outcomes.

Study Details

PMID:25148644
Participants:30
Impact:trial: 193.79 (3 mo), 262.06 (6 mo) vs control: 252.19 (3 mo), 342.32 (6 mo)
Trust score:3/5

bleeding time / general hemostasis

1 evidences

In healthy men, single IV doses of Revacept dose-dependently inhibited collagen-induced platelet aggregation without affecting bleeding time or general hemostasis.

Trust comment: Phase I first-in-human study with clear pharmacodynamic endpoints in 30 healthy volunteers, but small sample and early-phase design.

Study Details

PMID:21502572
Participants:30
Impact:no significant change
Trust score:3/5

surgical-site infection (any)

1 evidences

Phase 3 randomized trial: adding a gentamicin-collagen sponge at wound closure increased surgical-site infections compared with standard care.

Trust comment: Large multicenter randomized phase 3 RCT with clear, statistically significant results showing harm from the gentamicin-collagen sponge.

Study Details

PMID:20825316
Participants:602
Impact:30.0% (sponge) vs 20.9% (control); +9.1 percentage points (P=0.01)
Trust score:4/5

superficial surgical-site infection

1 evidences

Phase 3 randomized trial: adding a gentamicin-collagen sponge at wound closure increased surgical-site infections compared with standard care.

Trust comment: Large multicenter randomized phase 3 RCT with clear, statistically significant results showing harm from the gentamicin-collagen sponge.

Study Details

PMID:20825316
Participants:602
Impact:20.3% vs 13.6%; +6.7 percentage points (P=0.03)
Trust score:4/5

wound-related ER/office visits

1 evidences

Phase 3 randomized trial: adding a gentamicin-collagen sponge at wound closure increased surgical-site infections compared with standard care.

Trust comment: Large multicenter randomized phase 3 RCT with clear, statistically significant results showing harm from the gentamicin-collagen sponge.

Study Details

PMID:20825316
Participants:602
Impact:19.7% vs 11.0%; +8.7 percentage points (P=0.004)
Trust score:4/5

circulating collagen markers (ICTP, PICP, PIIINP, PINP)

1 evidences

Four-year randomized substudy comparing losartan vs atenolol: no long-term differences in circulating collagen markers or LV mass, though first-year PICP change predicted later LV mass regression with losartan.

Trust comment: Randomized substudy with 185 completers over 4 years; appropriate longitudinal measurements though secondary analysis.

Study Details

PMID:17078155
Participants:185
Impact:no significant difference between losartan and atenolol beyond first year
Trust score:4/5

left ventricular mass index (LVMI)

1 evidences

Four-year randomized substudy comparing losartan vs atenolol: no long-term differences in circulating collagen markers or LV mass, though first-year PICP change predicted later LV mass regression with losartan.

Trust comment: Randomized substudy with 185 completers over 4 years; appropriate longitudinal measurements though secondary analysis.

Study Details

PMID:17078155
Participants:185
Impact:no significant long-term change between treatment groups
Trust score:4/5

PICP first-year change — prediction of LVMI

1 evidences

Four-year randomized substudy comparing losartan vs atenolol: no long-term differences in circulating collagen markers or LV mass, though first-year PICP change predicted later LV mass regression with losartan.

Trust comment: Randomized substudy with 185 completers over 4 years; appropriate longitudinal measurements though secondary analysis.

Study Details

PMID:17078155
Participants:185
Impact:first-year PICP change correlated with LVMI reduction at 2–3 years in losartan group (r=0.28–0.29, P<0.05)
Trust score:4/5

collagen content in plaque

1 evidences

Small clinical comparison: 3 months of pravastatin before carotid endarterectomy increased plaque collagen and TIMP-1 and decreased lipid, inflammation, MMP-2, and cell death.

Trust comment: Human tissue study with objective histology but very small, nonrandomized groups limiting generalizability.

Study Details

PMID:11181465
Participants:24
Impact:12.4% vs 7.5% of plaque area (+4.9 percentage points; P<0.005)
Trust score:3/5

lipid content (oil red O)

1 evidences

Small clinical comparison: 3 months of pravastatin before carotid endarterectomy increased plaque collagen and TIMP-1 and decreased lipid, inflammation, MMP-2, and cell death.

Trust comment: Human tissue study with objective histology but very small, nonrandomized groups limiting generalizability.

Study Details

PMID:11181465
Participants:24
Impact:8.2% vs 23.9% (−15.7 percentage points; P<0.05)
Trust score:3/5

cell death by TUNEL

1 evidences

Small clinical comparison: 3 months of pravastatin before carotid endarterectomy increased plaque collagen and TIMP-1 and decreased lipid, inflammation, MMP-2, and cell death.

Trust comment: Human tissue study with objective histology but very small, nonrandomized groups limiting generalizability.

Study Details

PMID:11181465
Participants:24
Impact:17.7% vs 32.0% (−14.3 percentage points; P<0.05)
Trust score:3/5

cross-linked N-telopeptide of type I collagen (urine)

1 evidences

Double-blind randomized study in postmenopausal women: sublingual hormone therapy reduced bone turnover including type I collagen N-telopeptide and increased spine and hip BMD over 12 months.

Trust comment: Double-blind randomized study with clear biomarker and BMD changes though moderate sample size.

Study Details

PMID:10993031
Participants:57
Impact:−24.4% (HRT) and −39.5% (HRT+T)
Trust score:4/5

total hip bone mineral density

2 evidences

Bazedoxifene/conjugated estrogens increased spine and hip bone mineral density and reduced bone turnover markers versus placebo in postmenopausal women at risk for osteoporosis.

Trust comment: Large, randomized, double-blind, phase 3 trial providing high-quality evidence for BMD and marker changes.

Study Details

PMID:19635616
Participants:3397
Impact:significant increase versus placebo (all BZA/CE doses)
Trust score:4/5

Double-blind randomized study in postmenopausal women: sublingual hormone therapy reduced bone turnover including type I collagen N-telopeptide and increased spine and hip BMD over 12 months.

Trust comment: Double-blind randomized study with clear biomarker and BMD changes though moderate sample size.

Study Details

PMID:10993031
Participants:57
Impact:+0.4% (HRT) and +1.8% (HRT+T; P<0.05)
Trust score:4/5

IL-17A expression

1 evidences

Weekly injections of polymerized type I collagen reduced inflammatory signals and improved skin structure in patients with localized scleroderma.

Trust comment: Human clinical treatment with collagen in a small non-blinded cohort with tissue biopsies supports biological effects, but sample size is small and design details limit confidence.

Study Details

PMID:22731679
Participants:31
Impact:decreased
Trust score:3/5

IL-22 expression

1 evidences

Weekly injections of polymerized type I collagen reduced inflammatory signals and improved skin structure in patients with localized scleroderma.

Trust comment: Human clinical treatment with collagen in a small non-blinded cohort with tissue biopsies supports biological effects, but sample size is small and design details limit confidence.

Study Details

PMID:22731679
Participants:31
Impact:decreased
Trust score:3/5

TGF-β1 expression

1 evidences

Weekly injections of polymerized type I collagen reduced inflammatory signals and improved skin structure in patients with localized scleroderma.

Trust comment: Human clinical treatment with collagen in a small non-blinded cohort with tissue biopsies supports biological effects, but sample size is small and design details limit confidence.

Study Details

PMID:22731679
Participants:31
Impact:decreased
Trust score:3/5

Foxp3-expressing regulatory T cells (Tregs) in skin

1 evidences

Weekly injections of polymerized type I collagen reduced inflammatory signals and improved skin structure in patients with localized scleroderma.

Trust comment: Human clinical treatment with collagen in a small non-blinded cohort with tissue biopsies supports biological effects, but sample size is small and design details limit confidence.

Study Details

PMID:22731679
Participants:31
Impact:increased
Trust score:3/5

Skin architecture

1 evidences

Weekly injections of polymerized type I collagen reduced inflammatory signals and improved skin structure in patients with localized scleroderma.

Trust comment: Human clinical treatment with collagen in a small non-blinded cohort with tissue biopsies supports biological effects, but sample size is small and design details limit confidence.

Study Details

PMID:22731679
Participants:31
Impact:restored/normalized
Trust score:3/5

Skin thickness (modified Rodnan skin score, MRSS) - overall

1 evidences

Oral bovine type I collagen did not improve skin scores overall in diffuse cutaneous systemic sclerosis, but a late-phase subgroup showed greater skin score improvement at month 15.

Trust comment: Large randomized double-blind placebo-controlled trial directly testing oral type I collagen; overall null primary result but credible subgroup signal—well conducted though subgroup finding is exploratory.

Study Details

PMID:18512816
Participants:168
Impact:no significant change vs placebo at 12 and 15 months
Trust score:4/5

Skin thickness (MRSS) - late-phase subgroup

1 evidences

Oral bovine type I collagen did not improve skin scores overall in diffuse cutaneous systemic sclerosis, but a late-phase subgroup showed greater skin score improvement at month 15.

Trust comment: Large randomized double-blind placebo-controlled trial directly testing oral type I collagen; overall null primary result but credible subgroup signal—well conducted though subgroup finding is exploratory.

Study Details

PMID:18512816
Participants:168
Impact:improved at month 15: change −7.9 (collagen) vs −2.9 (placebo), P=0.0063
Trust score:4/5

immediate hemostasis (Angio-Seal vs Closer S)

1 evidences

A collagen-plug closure device (Angio-Seal) produced slightly higher immediate hemostasis and total success than a suture device, with similar complication rates.

Trust comment: Large prospective randomized dataset (1,676 cases) with objective outcome measures; applicable to collagen plug device but not systemic collagen supplementation.

Study Details

PMID:16549954
Participants:1676
Impact:95.2% vs 89.5% (+5.7%; p<0.001)
Trust score:4/5

total success rate (Angio-Seal vs Closer S)

1 evidences

A collagen-plug closure device (Angio-Seal) produced slightly higher immediate hemostasis and total success than a suture device, with similar complication rates.

Trust comment: Large prospective randomized dataset (1,676 cases) with objective outcome measures; applicable to collagen plug device but not systemic collagen supplementation.

Study Details

PMID:16549954
Participants:1676
Impact:92.6% vs 87.8% (+4.8%; p<0.01)
Trust score:4/5

early/late complications

1 evidences

A collagen-plug closure device (Angio-Seal) produced slightly higher immediate hemostasis and total success than a suture device, with similar complication rates.

Trust comment: Large prospective randomized dataset (1,676 cases) with objective outcome measures; applicable to collagen plug device but not systemic collagen supplementation.

Study Details

PMID:16549954
Participants:1676
Impact:no significant difference between devices
Trust score:4/5

overall lymphatic drainage

1 evidences

Topical type I collagen powder showed a non-significant trend to less overall drainage; in patients with >10 nodes removed it significantly reduced lymphorrhea volume and duration.

Trust comment: Randomized controlled trial (n=80) with clinically relevant endpoints; subgroup benefit when >10 nodes removed but overall primary outcomes not significant.

Study Details

PMID:21614910
Participants:80
Impact:non-significant trend toward lower total drainage in collagen group
Trust score:4/5

postoperative pain and morbidity

1 evidences

Topical type I collagen powder showed a non-significant trend to less overall drainage; in patients with >10 nodes removed it significantly reduced lymphorrhea volume and duration.

Trust comment: Randomized controlled trial (n=80) with clinically relevant endpoints; subgroup benefit when >10 nodes removed but overall primary outcomes not significant.

Study Details

PMID:21614910
Participants:80
Impact:no significant difference between groups
Trust score:4/5

lymphorrhea in >10 nodes subgroup

1 evidences

Topical type I collagen powder showed a non-significant trend to less overall drainage; in patients with >10 nodes removed it significantly reduced lymphorrhea volume and duration.

Trust comment: Randomized controlled trial (n=80) with clinically relevant endpoints; subgroup benefit when >10 nodes removed but overall primary outcomes not significant.

Study Details

PMID:21614910
Participants:80
Impact:significantly less volume and shorter duration with collagen (subgroup analysis)
Trust score:4/5

Clinical success (good/excellent results)

1 evidences

Randomized trial comparing periosteum cover vs type I/III collagen membrane for knee chondral repair; 2-year follow-up.

Trust comment: Randomized prospective human trial with 2-year follow-up and clear outcome metrics, though moderate sample size.

Study Details

PMID:16644224
Participants:68
Impact:+7 percentage points (74% ACI-C vs 67% ACI-P at 2 years)
Trust score:4/5

Graft hypertrophy requiring shaving

1 evidences

Randomized trial comparing periosteum cover vs type I/III collagen membrane for knee chondral repair; 2-year follow-up.

Trust comment: Randomized prospective human trial with 2-year follow-up and clear outcome metrics, though moderate sample size.

Study Details

PMID:16644224
Participants:68
Impact:36.4% in ACI-P vs 0% in ACI-C at 1 year (ACI-C lower)
Trust score:4/5

CTX (type I collagen resorption marker)

1 evidences

Oral alendronate and yearly zoledronic acid similarly increased bone density and strongly reduced bone resorption biomarkers in adults with osteogenesis imperfecta.

Trust comment: Prospective randomized 24-month study with 52 completers showing consistent BMD gains and large decreases in collagen resorption marker; well-reported outcomes.

Study Details

PMID:27482615
Participants:52
Impact:-58.0% (ALN) / -63.6% (ZOL)
Trust score:4/5

Swollen joint count

1 evidences

Double-blind placebo-controlled trial: intramuscular porcine type I collagen-PVP vs placebo in active rheumatoid arthritis over 6 months.

Trust comment: Randomized double-blind placebo-controlled human trial showing multiple statistically significant clinical endpoints, but small sample size limits generalizability.

Study Details

PMID:17181919
Participants:30
Impact:Decreased: 7.1 ±0.8 (collagen) vs 16.0 ±1.6 (placebo) at 6 months
Trust score:4/5

ACR response rates

1 evidences

Double-blind placebo-controlled trial: intramuscular porcine type I collagen-PVP vs placebo in active rheumatoid arthritis over 6 months.

Trust comment: Randomized double-blind placebo-controlled human trial showing multiple statistically significant clinical endpoints, but small sample size limits generalizability.

Study Details

PMID:17181919
Participants:30
Impact:ACR50: 57.1% (collagen) vs 0% (placebo); ACR20: 78.6% vs 71.4%
Trust score:4/5

CRP (inflammation)

2 evidences

Double-blind placebo-controlled trial: intramuscular porcine type I collagen-PVP vs placebo in active rheumatoid arthritis over 6 months.

Trust comment: Randomized double-blind placebo-controlled human trial showing multiple statistically significant clinical endpoints, but small sample size limits generalizability.

Study Details

PMID:17181919
Participants:30
Impact:Lower: 1.1 ±0.4 (collagen) vs 2.5 ±0.7 (placebo) at 6 months
Trust score:4/5

Biomarker sub-study of an RCT in RA showing tocilizumab reduces collagen-degradation biomarkers and CRP more than methotrexate by week 8.

Trust comment: Large, randomized phase‑3 trial sub-study with validated assays and appropriate statistics, but limited to short (8‑week) biomarker follow‑up.

Study Details

PMID:33413588
Participants:387
Impact:↓ 97% with tocilizumab vs placebo (MTX ↓27% vs placebo)
Trust score:4/5

knee passive range of motion (flexion)

1 evidences

12-week randomized placebo-controlled trial: small-dose undenatured type II collagen improved knee flexibility, reduced joint discomfort, and improved motor function versus placebo.

Trust comment: Randomized, double-blind, placebo-controlled RCT directly testing collagen supplement but relatively small sample (pilot-sized) so moderate-high confidence.

Study Details

PMID:35512781
Participants:58
Impact:significant improvement vs placebo (observed at 4, 8, 12 weeks)
Trust score:4/5

motor function (10-meter walk and stair-climbing)

1 evidences

12-week randomized placebo-controlled trial: small-dose undenatured type II collagen improved knee flexibility, reduced joint discomfort, and improved motor function versus placebo.

Trust comment: Randomized, double-blind, placebo-controlled RCT directly testing collagen supplement but relatively small sample (pilot-sized) so moderate-high confidence.

Study Details

PMID:35512781
Participants:58
Impact:significant improvement vs placebo
Trust score:4/5

objective incidence of Frey's syndrome (MSIT)

1 evidences

Placing acellular dermis during parotidectomy markedly reduced objective Frey's syndrome on starch-iodine testing but increased some postoperative complications.

Trust comment: Randomized clinical study using a collagen-derived graft with objective testing but small sample and higher complications reduce overall confidence.

Study Details

PMID:11801985
Participants:64
Impact:0% (acellular dermis) vs 40% (control) in tested subset (n=30)
Trust score:3/5

subjective incidence of Frey's syndrome (questionnaire)

1 evidences

Placing acellular dermis during parotidectomy markedly reduced objective Frey's syndrome on starch-iodine testing but increased some postoperative complications.

Trust comment: Randomized clinical study using a collagen-derived graft with objective testing but small sample and higher complications reduce overall confidence.

Study Details

PMID:11801985
Participants:64
Impact:3.1% (acellular dermis) vs 9.3% (control) overall
Trust score:3/5

complication rate (seroma/wound infection)

1 evidences

Placing acellular dermis during parotidectomy markedly reduced objective Frey's syndrome on starch-iodine testing but increased some postoperative complications.

Trust comment: Randomized clinical study using a collagen-derived graft with objective testing but small sample and higher complications reduce overall confidence.

Study Details

PMID:11801985
Participants:64
Impact:25% (acellular dermis) vs 9% (control)
Trust score:3/5

joint pain at rest (physician-assessed)

1 evidences

24-week randomized, double-blind trial in athletes: collagen hydrolysate reduced several measures of activity-related joint pain versus placebo, with stronger effects in a knee-arthralgia subgroup.

Trust comment: Randomized, double-blind, placebo-controlled trial directly testing collagen supplement but with missing data (only 97/147 evaluable) and subgroup analyses; moderate-high confidence.

Study Details

PMID:18416885
Participants:97
Impact:mean change -1.37 ±1.78 (collagen) vs -0.90 ±1.74 (placebo), p=0.025
Trust score:4/5

joint pain when walking (participant-assessed)

1 evidences

24-week randomized, double-blind trial in athletes: collagen hydrolysate reduced several measures of activity-related joint pain versus placebo, with stronger effects in a knee-arthralgia subgroup.

Trust comment: Randomized, double-blind, placebo-controlled trial directly testing collagen supplement but with missing data (only 97/147 evaluable) and subgroup analyses; moderate-high confidence.

Study Details

PMID:18416885
Participants:97
Impact:mean change -1.11 ±1.98 (collagen) vs -0.46 ±1.63 (placebo), p=0.007
Trust score:4/5

joint pain when standing (participant-assessed)

1 evidences

24-week randomized, double-blind trial in athletes: collagen hydrolysate reduced several measures of activity-related joint pain versus placebo, with stronger effects in a knee-arthralgia subgroup.

Trust comment: Randomized, double-blind, placebo-controlled trial directly testing collagen supplement but with missing data (only 97/147 evaluable) and subgroup analyses; moderate-high confidence.

Study Details

PMID:18416885
Participants:97
Impact:mean change -0.97 ±1.92 (collagen) vs -0.43 ±1.74 (placebo), p=0.011
Trust score:4/5

HbA1c reduction

1 evidences

Higher baseline endotrophin (a procollagen VI fragment) identified patients who showed better glycemic responses and fewer PPARγ-related adverse effects.

Trust comment: Post hoc secondary analysis of a randomized trial with a substantial sample (n=297), but secondary analysis reduces causal certainty.

Study Details

PMID:27631136
Participants:297
Impact:Upper two endotrophin tertiles had higher odds of ≥1% HbA1c reduction (OR 3.83) and ≥0.5% reduction (OR 3.85) at 26 weeks
Trust score:3/5

fasting serum glucose

1 evidences

Higher baseline endotrophin (a procollagen VI fragment) identified patients who showed better glycemic responses and fewer PPARγ-related adverse effects.

Trust comment: Post hoc secondary analysis of a randomized trial with a substantial sample (n=297), but secondary analysis reduces causal certainty.

Study Details

PMID:27631136
Participants:297
Impact:Significant reductions at week 26 only in upper two endotrophin tertiles (vs baseline)
Trust score:3/5

PPARγ-associated oedema

1 evidences

Higher baseline endotrophin (a procollagen VI fragment) identified patients who showed better glycemic responses and fewer PPARγ-related adverse effects.

Trust comment: Post hoc secondary analysis of a randomized trial with a substantial sample (n=297), but secondary analysis reduces causal certainty.

Study Details

PMID:27631136
Participants:297
Impact:Moderate-to-severe lower extremity oedema occurred only in the lower endotrophin tertile (i.e., less frequent in high endotrophin)
Trust score:3/5

BSAP (bone-specific alkaline phosphatase)

1 evidences

Infliximab induction increased markers of bone formation and resorption in children with Crohn's disease and these changes associated with improved growth and disease activity.

Trust comment: Well-characterized multicenter pediatric trial with objective biomarker and growth outcomes, though specific effect sizes for some markers are not provided here.

Study Details

PMID:19081527
Participants:112
Impact:Increased during induction (P < .001)
Trust score:4/5

CTX-1 (urine C‑telopeptide of type I collagen)

1 evidences

Infliximab induction increased markers of bone formation and resorption in children with Crohn's disease and these changes associated with improved growth and disease activity.

Trust comment: Well-characterized multicenter pediatric trial with objective biomarker and growth outcomes, though specific effect sizes for some markers are not provided here.

Study Details

PMID:19081527
Participants:112
Impact:Increased during induction (P < .001); change associated with improvements in height z-score
Trust score:4/5

mucosal recession (MR)

1 evidences

Residual defect height >1 mm after guided bone regeneration was associated with higher bleeding on probing and tended to increase mucosal recession at 4 years.

Trust comment: Four-year clinical follow-up is valuable, but small group sizes (n=24 total) limit precision and external validity.

Study Details

PMID:21806682
Participants:24
Impact:Tended to be greater in test groups (0.5±0.7 and 0.4±0.6 mm) vs control (0.2±0.3 mm), not statistically significant
Trust score:3/5

proximal femoral bone mineral density (BMD)

1 evidences

All cemented prosthesis designs led to early proximal femoral bone loss and transient increases in bone turnover markers; patterns were similar across designs.

Trust comment: Randomized clinical trial with 2-year follow-up and objective DXA and biochemical markers, supporting reliable within-study findings.

Study Details

PMID:23283370
Participants:120
Impact:Decreased over first year for all designs; greatest loss 14% in proximal medial femur (Gruen zone 7)
Trust score:4/5

N‑telopeptide of type‑I collagen (urine)

1 evidences

All cemented prosthesis designs led to early proximal femoral bone loss and transient increases in bone turnover markers; patterns were similar across designs.

Trust comment: Randomized clinical trial with 2-year follow-up and objective DXA and biochemical markers, supporting reliable within-study findings.

Study Details

PMID:23283370
Participants:120
Impact:Transient increase over first year (marker of osteoclast activity)
Trust score:4/5

defect resolution percentage

1 evidences

Addition of deproteinized bovine bone mineral plus a collagen membrane produced greater radiographic bone fill of intrabony periodontal defects at 1 year versus flap surgery alone.

Trust comment: Multi-center randomized-controlled trial (n=120) with objective radiographic endpoints supports moderate-to-high trust in results.

Study Details

PMID:16634957
Participants:120
Impact:Greater resolution in test group; influenced by baseline defect depth and plaque score
Trust score:4/5

PIIANP and HELIX-II (cartilage turnover markers)

1 evidences

Tocilizumab plus methotrexate rapidly reduced cartilage turnover and proteolytic markers and reduced bone resorption while increasing bone formation markers in RA patients.

Trust comment: Large substudy (n=416) of a double-blind placebo-controlled trial with objective biochemical markers gives reasonable confidence in findings.

Study Details

PMID:20039425
Participants:416
Impact:Marked, dose-dependent reductions by week 4 that were maintained to week 24
Trust score:4/5

PINP (procollagen type I N‑propeptide)

1 evidences

Tocilizumab plus methotrexate rapidly reduced cartilage turnover and proteolytic markers and reduced bone resorption while increasing bone formation markers in RA patients.

Trust comment: Large substudy (n=416) of a double-blind placebo-controlled trial with objective biochemical markers gives reasonable confidence in findings.

Study Details

PMID:20039425
Participants:416
Impact:Increased at 4 weeks (significant vs placebo)
Trust score:4/5

CTX‑I and ICTP (bone resorption markers)

1 evidences

Tocilizumab plus methotrexate rapidly reduced cartilage turnover and proteolytic markers and reduced bone resorption while increasing bone formation markers in RA patients.

Trust comment: Large substudy (n=416) of a double-blind placebo-controlled trial with objective biochemical markers gives reasonable confidence in findings.

Study Details

PMID:20039425
Participants:416
Impact:Significant decreases, indicating reduced bone degradation
Trust score:4/5

labial plate percentage bone loss

1 evidences

In 30 patients (32 sockets) grafted with biphasic calcium phosphate, sites covered by a PEG synthetic membrane lost less labial and coronal bone percentage than sites covered by porcine collagen membrane at 22 weeks.

Trust comment: Randomized controlled trial with objective CBCT endpoints but relatively small sample (30 patients); results appear internally consistent.

Study Details

PMID:32799365
Participants:30
Impact:PEG -2.86% (SD 13.48) vs collagen 7.42% (SD 11.95) (difference ≈ -10.28 percentage points)
Trust score:4/5

coronal part percentage bone loss

1 evidences

In 30 patients (32 sockets) grafted with biphasic calcium phosphate, sites covered by a PEG synthetic membrane lost less labial and coronal bone percentage than sites covered by porcine collagen membrane at 22 weeks.

Trust comment: Randomized controlled trial with objective CBCT endpoints but relatively small sample (30 patients); results appear internally consistent.

Study Details

PMID:32799365
Participants:30
Impact:PEG 13.45% (SD 11.97) vs collagen 28.59% (SD 16.97) (difference ≈ -15.14 percentage points)
Trust score:4/5

defect width decrease

1 evidences

RCT comparing porcine-derived bioabsorbable collagen membrane versus ePTFE for GBR around implants; both membranes reduced defect dimensions, with some differences by metric.

Trust comment: Randomized controlled design with 6-month follow-up and objective surgical measures; moderate sample size and some reporting limitations.

Study Details

PMID:11128923
Participants:48
Impact:collagen 1.95 ±0.60 mm vs ePTFE 2.65 ±0.56 mm (at 6 months)
Trust score:4/5

defect length decrease

1 evidences

RCT comparing porcine-derived bioabsorbable collagen membrane versus ePTFE for GBR around implants; both membranes reduced defect dimensions, with some differences by metric.

Trust comment: Randomized controlled design with 6-month follow-up and objective surgical measures; moderate sample size and some reporting limitations.

Study Details

PMID:11128923
Participants:48
Impact:collagen 2.65 ±0.61 mm vs ePTFE 2.26 ±0.66 mm (at 6 months)
Trust score:4/5

defect circumference decrease (degrees)

1 evidences

RCT comparing porcine-derived bioabsorbable collagen membrane versus ePTFE for GBR around implants; both membranes reduced defect dimensions, with some differences by metric.

Trust comment: Randomized controlled design with 6-month follow-up and objective surgical measures; moderate sample size and some reporting limitations.

Study Details

PMID:11128923
Participants:48
Impact:collagen 57.7 ±18.7° vs ePTFE 80.2 ±19.9° (at 6 months)
Trust score:4/5

wound dehiscence rate

1 evidences

Absorbable plain gut (collagen-derived) sutures produced similar or slightly better long-term cosmetic outcomes than nylon sutures in children.

Trust comment: Randomized clinical trial in children comparing a collagen-derived suture to nylon with objective and blinded long-term assessment, though some loss to follow-up.

Study Details

PMID:15231459
Participants:63
Impact:-9 percentage points (2% vs 11%; plain gut vs nylon, p = 0.07)
Trust score:4/5

frequency of CAL gain ≥4 mm

1 evidences

Using a collagen membrane with bone graft produced similar tooth-supporting tissue gain as the alternative treatment over 12 months.

Trust comment: Randomized allocation with 12-month follow-up and objective clinical endpoints, but modest sample size limits precision.

Study Details

PMID:24835417
Participants:40
Impact:60% vs 50% (no significant difference)
Trust score:4/5

residual probing depth ≥6 mm

1 evidences

Using a collagen membrane with bone graft produced similar tooth-supporting tissue gain as the alternative treatment over 12 months.

Trust comment: Randomized allocation with 12-month follow-up and objective clinical endpoints, but modest sample size limits precision.

Study Details

PMID:24835417
Participants:40
Impact:5% vs 15% (no significant difference)
Trust score:4/5

cumulative live birth rate

1 evidences

A collagen scaffold seeded with hUC-MSCs led to a non-significant higher live-birth rate and significantly increased endometrial thickness; two patients developed transient urticaria.

Trust comment: Double-blind RCT using a collagen scaffold with objective clinical and molecular endpoints but small sample size limits statistical power for live-birth outcomes.

Study Details

PMID:40371958
Participants:24
Impact:27.3% (3/11) vs 7.7% (1/13), RR 3.55, P=0.30 (not significant)
Trust score:4/5

endometrial thickness (EmT)

1 evidences

A collagen scaffold seeded with hUC-MSCs led to a non-significant higher live-birth rate and significantly increased endometrial thickness; two patients developed transient urticaria.

Trust comment: Double-blind RCT using a collagen scaffold with objective clinical and molecular endpoints but small sample size limits statistical power for live-birth outcomes.

Study Details

PMID:40371958
Participants:24
Impact:Pre 5.3±0.7 → post 6.5±1.3 mm in hUC-MSC/CS group; Δ +1.2±1.2 mm (P=0.007)
Trust score:4/5

urticaria (adverse event)

1 evidences

A collagen scaffold seeded with hUC-MSCs led to a non-significant higher live-birth rate and significantly increased endometrial thickness; two patients developed transient urticaria.

Trust comment: Double-blind RCT using a collagen scaffold with objective clinical and molecular endpoints but small sample size limits statistical power for live-birth outcomes.

Study Details

PMID:40371958
Participants:24
Impact:2 of 11 patients in treatment group experienced urticaria
Trust score:4/5

procollagen type III (PC III)

1 evidences

In 81 hepatitis B patients randomized to Kangxian Baogan Decoction or standard care, the decoction group showed reductions in serum fibrosis markers and improved liver pathology.

Trust comment: Randomized clinical study with biopsy and multiple biomarker outcomes, but limited methodological detail in abstract and traditional decoction limits certainty.

Study Details

PMID:12584827
Participants:81
Impact:reduced after KXBGD treatment
Trust score:3/5

collagen type IV (C-IV)

1 evidences

In 81 hepatitis B patients randomized to Kangxian Baogan Decoction or standard care, the decoction group showed reductions in serum fibrosis markers and improved liver pathology.

Trust comment: Randomized clinical study with biopsy and multiple biomarker outcomes, but limited methodological detail in abstract and traditional decoction limits certainty.

Study Details

PMID:12584827
Participants:81
Impact:reduced after KXBGD treatment
Trust score:3/5

plasma salmon calcitonin exposure

1 evidences

Two randomized double‑blind placebo‑controlled studies showed oral salmon calcitonin exposure varied between and within individuals; higher exposure correlated strongly with greater suppression of serum CTX‑I (bone resorption marker).

Trust comment: Randomized, double‑blind, placebo‑controlled design with clear biomarker correlations supports moderate-to-high trustworthiness.

Study Details

PMID:19813008
Participants:130
Impact:high inter- and intraindividual variability (CV 22–34%)
Trust score:4/5

serum CTX‑I (bone resorption marker)

1 evidences

Two randomized double‑blind placebo‑controlled studies showed oral salmon calcitonin exposure varied between and within individuals; higher exposure correlated strongly with greater suppression of serum CTX‑I (bone resorption marker).

Trust comment: Randomized, double‑blind, placebo‑controlled design with clear biomarker correlations supports moderate-to-high trustworthiness.

Study Details

PMID:19813008
Participants:130
Impact:suppression correlated with sCT exposure (Pearson r = -0.74 to -0.96 for single doses)
Trust score:4/5

serum CTX (s-CTX)

1 evidences

In two randomized placebo‑controlled studies in 81 postmenopausal women, bedtime GLP‑2 injections produced a dose‑related reduction in the bone resorption marker s‑CTX and a trend toward increased osteocalcin.

Trust comment: Well‑designed randomized placebo‑controlled studies with biologic markers and adequate sample size support reasonable confidence.

Study Details

PMID:14751571
Participants:81
Impact:dose-related reduction after GLP-2 injection (AUC0–10h decrease; P < 0.05)
Trust score:4/5

early postoperative complications

1 evidences

Placing a gentamycin-containing collagen sponge after rectal cancer surgery reduced early postoperative complications and improved 3-year survival.

Trust comment: Randomized clinical trial with 218 analyzed and 3-year follow-up showing clear clinical endpoints, though mechanism for metastasis reduction is unclear.

Study Details

PMID:15375668
Participants:218
Impact:-16.8 percentage points (20.7% vs 37.5%; p=0.044)
Trust score:4/5

overall survival after R0 resection (36 months)

1 evidences

Placing a gentamycin-containing collagen sponge after rectal cancer surgery reduced early postoperative complications and improved 3-year survival.

Trust comment: Randomized clinical trial with 218 analyzed and 3-year follow-up showing clear clinical endpoints, though mechanism for metastasis reduction is unclear.

Study Details

PMID:15375668
Participants:218
Impact:+14.7 percentage points (88.66% vs 73.96%)
Trust score:4/5

distant metastasis rate

1 evidences

Placing a gentamycin-containing collagen sponge after rectal cancer surgery reduced early postoperative complications and improved 3-year survival.

Trust comment: Randomized clinical trial with 218 analyzed and 3-year follow-up showing clear clinical endpoints, though mechanism for metastasis reduction is unclear.

Study Details

PMID:15375668
Participants:218
Impact:reduced (significant; absolute rates not provided)
Trust score:4/5

implant failure

2 evidences

Double-blind RCT comparing bovine bone + membrane vs pure β-tricalcium phosphate (a calcium phosphate) + membrane for horizontal augmentation: no major differences, with a small (0.24 mm) less peri-implant radiographic bone loss favoring the β-TCP group.

Trust comment: Double-blind randomized controlled trial with blinded outcome assessment (n=50); objective measures but modest sample size.

Study Details

PMID:26355171
Participants:50
Impact:0% (no implant failures)
Trust score:4/5

Randomized trial (78 enrolled, 8 excluded/dropouts = 70 completed) comparing internal socket grafting alone versus with additional buccal augmentation covered by collagen resorbable membranes; no significant differences at 6 months.

Trust comment: Multicenter randomized controlled trial with blinded assessors and reported outcomes; modest sample and short-term follow-up but directly uses collagen membranes as part of the intervention.

Study Details

PMID:24179978
Participants:70
Impact:no significant difference (IEG 2 vs ISGA 1)
Trust score:4/5

vertical defect bone gain

1 evidences

Double-blind RCT comparing bovine bone + membrane vs pure β-tricalcium phosphate (a calcium phosphate) + membrane for horizontal augmentation: no major differences, with a small (0.24 mm) less peri-implant radiographic bone loss favoring the β-TCP group.

Trust comment: Double-blind randomized controlled trial with blinded outcome assessment (n=50); objective measures but modest sample size.

Study Details

PMID:26355171
Participants:50
Impact:-0.15 mm difference (BB vs CJ; not significant; P=0.5504) favoring BB
Trust score:4/5

horizontal defect bone gain

1 evidences

Double-blind RCT comparing bovine bone + membrane vs pure β-tricalcium phosphate (a calcium phosphate) + membrane for horizontal augmentation: no major differences, with a small (0.24 mm) less peri-implant radiographic bone loss favoring the β-TCP group.

Trust comment: Double-blind randomized controlled trial with blinded outcome assessment (n=50); objective measures but modest sample size.

Study Details

PMID:26355171
Participants:50
Impact:-0.27 mm difference (BB vs CJ; not significant) favoring BB
Trust score:4/5

radiographic peri-implant marginal bone loss

1 evidences

Double-blind RCT comparing bovine bone + membrane vs pure β-tricalcium phosphate (a calcium phosphate) + membrane for horizontal augmentation: no major differences, with a small (0.24 mm) less peri-implant radiographic bone loss favoring the β-TCP group.

Trust comment: Double-blind randomized controlled trial with blinded outcome assessment (n=50); objective measures but modest sample size.

Study Details

PMID:26355171
Participants:50
Impact:0.24 mm difference favoring CJ (P=0.0464)
Trust score:4/5

muscle soreness (DOMS)

1 evidences

When consumed for three days after downhill running, collagen hydrolysate did not improve muscle soreness, muscle function, or blood markers of muscle damage compared with dairy protein or placebo.

Trust comment: Double-blind, placebo-controlled randomized trial (n=33) with appropriate measures; modest sample size but valid design.

Study Details

PMID:39771010
Participants:33
Impact:no significant treatment effect (no difference CH vs DP vs PLA)
Trust score:4/5

muscle function (CMJ, IMTP, MVIC, running economy)

1 evidences

When consumed for three days after downhill running, collagen hydrolysate did not improve muscle soreness, muscle function, or blood markers of muscle damage compared with dairy protein or placebo.

Trust comment: Double-blind, placebo-controlled randomized trial (n=33) with appropriate measures; modest sample size but valid design.

Study Details

PMID:39771010
Participants:33
Impact:no differences between treatments across time
Trust score:4/5

blood markers (CK, hsCRP, IL-6)

1 evidences

When consumed for three days after downhill running, collagen hydrolysate did not improve muscle soreness, muscle function, or blood markers of muscle damage compared with dairy protein or placebo.

Trust comment: Double-blind, placebo-controlled randomized trial (n=33) with appropriate measures; modest sample size but valid design.

Study Details

PMID:39771010
Participants:33
Impact:no treatment effects (all markers changed over time due to exercise but not by supplement)
Trust score:4/5

Clinical success rate

1 evidences

Multicenter randomized trial comparing rhOP-1 delivered in a type I collagen carrier versus autograft for tibial nonunions; clinical and radiographic healing were similar between groups.

Trust comment: Large, randomized multicenter trial with clear clinical endpoints; direct use of type I collagen as a carrier supports relevance but collagen was not the sole active therapy.

Study Details

PMID:11314793
Participants:122
Impact:OP-1+type I collagen carrier 81% vs autograft 85% at 9 months (no significant difference, p=0.524)
Trust score:4/5

Radiographic healing

1 evidences

Multicenter randomized trial comparing rhOP-1 delivered in a type I collagen carrier versus autograft for tibial nonunions; clinical and radiographic healing were similar between groups.

Trust comment: Large, randomized multicenter trial with clear clinical endpoints; direct use of type I collagen as a carrier supports relevance but collagen was not the sole active therapy.

Study Details

PMID:11314793
Participants:122
Impact:OP-1+collagen 75% vs autograft 84% at 9 months (no significant difference, p=0.218)
Trust score:4/5

Adverse events / donor-site morbidity

1 evidences

Multicenter randomized trial comparing rhOP-1 delivered in a type I collagen carrier versus autograft for tibial nonunions; clinical and radiographic healing were similar between groups.

Trust comment: Large, randomized multicenter trial with clear clinical endpoints; direct use of type I collagen as a carrier supports relevance but collagen was not the sole active therapy.

Study Details

PMID:11314793
Participants:122
Impact:Serious events 44% in each group (none related to graft); >20% chronic donor-site pain in autograft group
Trust score:4/5

C-Telopeptide of Type I Collagen (CTx-1)

1 evidences

In Chinese postmenopausal women, daily fortified milk (1200 mg calcium + vitamin D + FOS-inulin) for 52 weeks increased 25(OH)D, suppressed bone turnover markers and preserved femoral neck BMD compared with regular milk.

Trust comment: Randomized controlled trial with relevant biochemical and BMD outcomes; well-reported markers though intervention included multiple nutrients, not collagen alone.

Study Details

PMID:28975432
Participants:121
Impact:Significant suppression in intervention group (p=0.018)
Trust score:4/5

Procollagen I N-Terminal Propeptide (PINP)

1 evidences

In Chinese postmenopausal women, daily fortified milk (1200 mg calcium + vitamin D + FOS-inulin) for 52 weeks increased 25(OH)D, suppressed bone turnover markers and preserved femoral neck BMD compared with regular milk.

Trust comment: Randomized controlled trial with relevant biochemical and BMD outcomes; well-reported markers though intervention included multiple nutrients, not collagen alone.

Study Details

PMID:28975432
Participants:121
Impact:Significant suppression in intervention group (p=0.004)
Trust score:4/5

Plasma 25(OH)D

1 evidences

In Chinese postmenopausal women, daily fortified milk (1200 mg calcium + vitamin D + FOS-inulin) for 52 weeks increased 25(OH)D, suppressed bone turnover markers and preserved femoral neck BMD compared with regular milk.

Trust comment: Randomized controlled trial with relevant biochemical and BMD outcomes; well-reported markers though intervention included multiple nutrients, not collagen alone.

Study Details

PMID:28975432
Participants:121
Impact:Increased to 74.8 nmol/L (intervention) vs 63.1 nmol/L (control), p<0.001
Trust score:4/5

Patient global assessment improvement >10 mm

1 evidences

Analysis of two RCTs (including one of oral type I collagen) assessing sensitivity of MRSS body sites; total MRSS showed large effect sizes and some sites (hands, forearms, chest) were more sensitive to change.

Trust comment: Large RCT data analyzed for outcome sensitivity; collagen was an intervention in one trial but full trial-level results are not detailed here.

Study Details

PMID:19605370
Participants:129
Impact:Collagen trial: 54 of 129 patients (42%) improved >10 mm at 12 months
Trust score:4/5

Total modified Rodnan skin score (MRSS)

1 evidences

Analysis of two RCTs (including one of oral type I collagen) assessing sensitivity of MRSS body sites; total MRSS showed large effect sizes and some sites (hands, forearms, chest) were more sensitive to change.

Trust comment: Large RCT data analyzed for outcome sensitivity; collagen was an intervention in one trial but full trial-level results are not detailed here.

Study Details

PMID:19605370
Participants:129
Impact:Large effect size (0.85–0.98) reported across trials including the collagen study
Trust score:4/5

Body-site effect sizes (hands, forearms, chest)

1 evidences

Analysis of two RCTs (including one of oral type I collagen) assessing sensitivity of MRSS body sites; total MRSS showed large effect sizes and some sites (hands, forearms, chest) were more sensitive to change.

Trust comment: Large RCT data analyzed for outcome sensitivity; collagen was an intervention in one trial but full trial-level results are not detailed here.

Study Details

PMID:19605370
Participants:129
Impact:Moderate effect sizes (0.50–0.74); other sites smaller (0.16–0.49)
Trust score:4/5

Probing pocket depth (PPD) and probing defect depth (PDD)

1 evidences

Randomized study of immediate molar implants using autologous bone chips, a collagen membrane (Ossix), or both; after 12 months all groups had similar modest marginal bone loss.

Trust comment: Randomized prospective design with clinical and radiographic endpoints; moderate follow-up losses but relevant use of a collagen membrane.

Study Details

PMID:22117841
Participants:76
Impact:No differences between groups in PPD or PDD at 12 months
Trust score:4/5

Implant survival/failures

1 evidences

Randomized study of immediate molar implants using autologous bone chips, a collagen membrane (Ossix), or both; after 12 months all groups had similar modest marginal bone loss.

Trust comment: Randomized prospective design with clinical and radiographic endpoints; moderate follow-up losses but relevant use of a collagen membrane.

Study Details

PMID:22117841
Participants:76
Impact:15 implants judged failures at re-entry; no additional implant losses during follow-up reported
Trust score:4/5

number of antiglaucoma medications

1 evidences

A porcine collagen implant (Ologen) used during trabeculectomy lowered intraocular pressure similarly to mitomycin‑C over 5 years with comparable safety.

Trust comment: Randomized, masked trial with 5-year follow-up but small sample (n=40) limits power for secondary endpoints.

Study Details

PMID:26946419
Participants:40
Impact:from 2.6 to 1.4 in Ologen group (−1.2 meds; ≈−46%)
Trust score:4/5

thin avascular bleb frequency

1 evidences

A porcine collagen implant (Ologen) used during trabeculectomy lowered intraocular pressure similarly to mitomycin‑C over 5 years with comparable safety.

Trust comment: Randomized, masked trial with 5-year follow-up but small sample (n=40) limits power for secondary endpoints.

Study Details

PMID:26946419
Participants:40
Impact:10% in Ologen vs 30% in MMC (difference not statistically significant, P=0.235)
Trust score:4/5

probing attachment level (PAL) gain

1 evidences

Guided tissue regeneration with a collagen membrane plus Bio‑Oss produced clinical improvements similar to a PLA/PGA membrane at 1 year.

Trust comment: Randomized trial with small sample and 1-year follow-up; results indicate comparable performance but limited size.

Study Details

PMID:15583920
Participants:28
Impact:3.9 mm (collagen membrane) vs 2.9 mm (PLA/PGA); no significant difference
Trust score:3/5

residual probing pocket depth (PPD)

1 evidences

Guided tissue regeneration with a collagen membrane plus Bio‑Oss produced clinical improvements similar to a PLA/PGA membrane at 1 year.

Trust comment: Randomized trial with small sample and 1-year follow-up; results indicate comparable performance but limited size.

Study Details

PMID:15583920
Participants:28
Impact:4.1 mm (collagen membrane) vs 4.8 mm (PLA/PGA); no significant difference
Trust score:3/5

defect length change (ΔDL)

1 evidences

Cross‑linked collagen membrane supported bone regeneration comparable to a native collagen membrane; premature membrane exposure was linked to soft‑tissue inflammation.

Trust comment: Multicenter, randomized, double-blinded design with reasonable sample size; some exclusions and infections noted but overall high quality.

Study Details

PMID:19302393
Participants:49
Impact:Mean ΔDL 3.0 mm (cross-linked VN) vs 1.94 mm (native BG); VN non-inferior to BG
Trust score:4/5

tissue quality (TQ)

1 evidences

Cross‑linked collagen membrane supported bone regeneration comparable to a native collagen membrane; premature membrane exposure was linked to soft‑tissue inflammation.

Trust comment: Multicenter, randomized, double-blinded design with reasonable sample size; some exclusions and infections noted but overall high quality.

Study Details

PMID:19302393
Participants:49
Impact:VN 3.05 vs BG 3.46 (comparable; no significant difference)
Trust score:4/5

membrane exposure — inflammation

1 evidences

Cross‑linked collagen membrane supported bone regeneration comparable to a native collagen membrane; premature membrane exposure was linked to soft‑tissue inflammation.

Trust comment: Multicenter, randomized, double-blinded design with reasonable sample size; some exclusions and infections noted but overall high quality.

Study Details

PMID:19302393
Participants:49
Impact:Premature exposure correlated with adjacent soft-tissue inflammation (noted in VN group)
Trust score:4/5

cartilage degradation (uCTX-II)

1 evidences

500 mg daily natural eggshell membrane (contains collagen I) vs placebo for 2 weeks reduced cartilage degradation and improved recovery from exercise-induced pain and stiffness in healthy postmenopausal women.

Trust comment: Randomized, double-blind, placebo-controlled human trial with complete follow-up but short duration (2 weeks) and modest sample size.

Study Details

PMID:29497287
Participants:60
Impact:-17.2% at 1 week; -9.9% at 2 weeks (treatment effect vs placebo)
Trust score:4/5

recovery (12-hour) pain

1 evidences

500 mg daily natural eggshell membrane (contains collagen I) vs placebo for 2 weeks reduced cartilage degradation and improved recovery from exercise-induced pain and stiffness in healthy postmenopausal women.

Trust comment: Randomized, double-blind, placebo-controlled human trial with complete follow-up but short duration (2 weeks) and modest sample size.

Study Details

PMID:29497287
Participants:60
Impact:improved (Day 8 onward), Day14 treatment effect −11.8% vs placebo
Trust score:4/5

recovery (12-hour) stiffness

1 evidences

500 mg daily natural eggshell membrane (contains collagen I) vs placebo for 2 weeks reduced cartilage degradation and improved recovery from exercise-induced pain and stiffness in healthy postmenopausal women.

Trust comment: Randomized, double-blind, placebo-controlled human trial with complete follow-up but short duration (2 weeks) and modest sample size.

Study Details

PMID:29497287
Participants:60
Impact:improved, Day14 treatment effect −56.3% vs placebo
Trust score:4/5

immediate stiffness

1 evidences

500 mg daily natural eggshell membrane (contains collagen I) vs placebo for 2 weeks reduced cartilage degradation and improved recovery from exercise-induced pain and stiffness in healthy postmenopausal women.

Trust comment: Randomized, double-blind, placebo-controlled human trial with complete follow-up but short duration (2 weeks) and modest sample size.

Study Details

PMID:29497287
Participants:60
Impact:treatment effect −18.5% (Day13)
Trust score:4/5

immediate pain (within-group)

1 evidences

500 mg daily natural eggshell membrane (contains collagen I) vs placebo for 2 weeks reduced cartilage degradation and improved recovery from exercise-induced pain and stiffness in healthy postmenopausal women.

Trust comment: Randomized, double-blind, placebo-controlled human trial with complete follow-up but short duration (2 weeks) and modest sample size.

Study Details

PMID:29497287
Participants:60
Impact:within-group decrease up to −38.1% (Day13) though overall trend vs placebo NS
Trust score:4/5

healing success (clinical/radiographic)

1 evidences

Randomized clinical assessment of guided-tissue regeneration using anorganic bovine bone plus a resorbable collagen membrane in periapical surgery; overall 1-year healing reported with possible benefit of GTR for transosseous (two-wall) lesions.

Trust comment: Randomized human surgical study using collagen membrane but limited reporting of group-level comparisons for membrane vs no-membrane and modest sample size.

Study Details

PMID:18533208
Participants:55
Impact:56/69 teeth healed at 1 year (81.2% overall)
Trust score:3/5

uncertain healing

1 evidences

Randomized clinical assessment of guided-tissue regeneration using anorganic bovine bone plus a resorbable collagen membrane in periapical surgery; overall 1-year healing reported with possible benefit of GTR for transosseous (two-wall) lesions.

Trust comment: Randomized human surgical study using collagen membrane but limited reporting of group-level comparisons for membrane vs no-membrane and modest sample size.

Study Details

PMID:18533208
Participants:55
Impact:10/69 teeth classified as uncertain at 1 year
Trust score:3/5

failure

1 evidences

Randomized clinical assessment of guided-tissue regeneration using anorganic bovine bone plus a resorbable collagen membrane in periapical surgery; overall 1-year healing reported with possible benefit of GTR for transosseous (two-wall) lesions.

Trust comment: Randomized human surgical study using collagen membrane but limited reporting of group-level comparisons for membrane vs no-membrane and modest sample size.

Study Details

PMID:18533208
Participants:55
Impact:3/69 teeth classified as failure at 1 year
Trust score:3/5

Objective anatomic cure (POP-Q <2)

1 evidences

Collagen-coated mesh gave better objective anatomical repair than conventional repair at 1 and 3 years, but patient-reported symptoms were similar.

Trust comment: Multicenter randomized controlled trial with 3-year follow-up and high follow-up rate supports good trustworthiness.

Study Details

PMID:26420345
Participants:138
Impact:mesh: 88.1% (1 yr) and 91.4% (3 yr) vs colporrhaphy: 39.9% (1 yr) and 41.2% (3 yr)
Trust score:4/5

Patient-reported pelvic floor symptoms

1 evidences

Collagen-coated mesh gave better objective anatomical repair than conventional repair at 1 and 3 years, but patient-reported symptoms were similar.

Trust comment: Multicenter randomized controlled trial with 3-year follow-up and high follow-up rate supports good trustworthiness.

Study Details

PMID:26420345
Participants:138
Impact:no significant difference between groups (PFIQ-7, PFDI-20, PISQ-12)
Trust score:4/5

Osseointegration (bone-DBBM contact %)

1 evidences

Using DBBM plus a porcine collagen membrane or matrix resulted in less new bone formation at 4 months than unassisted socket healing.

Trust comment: Randomized allocation with histomorphometric endpoints and objective measurements gives moderate-high reliability.

Study Details

PMID:39105326
Participants:42
Impact:GBR: 35.66% ±9.8; SS: 31.18% ±19.38
Trust score:4/5

Need for additional guided bone regeneration at implant placement

1 evidences

Alveolar ridge preservation using demineralized bovine bone with 10% collagen plus a collagen matrix reduced the need for additional bone grafting and attenuated ridge changes versus unassisted healing.

Trust comment: Randomized controlled design with radiographic and profilometric outcomes is of good quality though some data loss reduced sample size.

Study Details

PMID:38105498
Participants:55
Impact:ARP-CM: 31.6%; ARP-PG: 29.4%; unassisted control: 68.4% (higher need in control)
Trust score:4/5

Alveolar ridge change attenuation

1 evidences

Alveolar ridge preservation using demineralized bovine bone with 10% collagen plus a collagen matrix reduced the need for additional bone grafting and attenuated ridge changes versus unassisted healing.

Trust comment: Randomized controlled design with radiographic and profilometric outcomes is of good quality though some data loss reduced sample size.

Study Details

PMID:38105498
Participants:55
Impact:ARP reduced radiographic and profilometric alterations at 1 year versus unassisted healing (no single % provided)
Trust score:4/5

Urinary NTX (type I collagen N-telopeptide)

1 evidences

In third-trimester pregnant women, a bedtime 1200 mg calcium supplement reduced urinary markers of type I collagen breakdown (NTX) by about 14%.

Trust comment: Randomized crossover trial with daily urine collection and an objective validated biomarker showing a consistent, statistically significant effect.

Study Details

PMID:12657345
Participants:31
Impact:Mean decreased from 96.8 to 83.2 nM BCE/mM creatinine; mean reduction 13.6 nM (~14%), p<0.001; 27/31 (87.1%) showed reductions
Trust score:4/5

Clinical bone-regeneration success rate

1 evidences

In mandibular reconstruction, grafts with higher CD34+ cell concentrations (≥~200/mL) produced substantially better bone regeneration, higher radiographic density, and greater trabecular bone area; an absorbable collagen sponge was used as scaffold but CD34+ dose was the main variable.

Trust comment: Randomized clinical reconstruction study with objective radiographic and histomorphometric endpoints; collagen sponge was scaffold but not randomized variable.

Study Details

PMID:24683583
Participants:40
Impact:Group with higher CD34+ concentration: 100% vs low-CD34 group: 40% achieved primary endpoint
Trust score:4/5

Radiographic bone density (Hounsfield units)

1 evidences

In mandibular reconstruction, grafts with higher CD34+ cell concentrations (≥~200/mL) produced substantially better bone regeneration, higher radiographic density, and greater trabecular bone area; an absorbable collagen sponge was used as scaffold but CD34+ dose was the main variable.

Trust comment: Randomized clinical reconstruction study with objective radiographic and histomorphometric endpoints; collagen sponge was scaffold but not randomized variable.

Study Details

PMID:24683583
Participants:40
Impact:Low-CD34 group 424 ±115 HU vs high-CD34 group 731 ±98 HU (mean ± SD)
Trust score:4/5

Trabecular bone area (%)

1 evidences

In mandibular reconstruction, grafts with higher CD34+ cell concentrations (≥~200/mL) produced substantially better bone regeneration, higher radiographic density, and greater trabecular bone area; an absorbable collagen sponge was used as scaffold but CD34+ dose was the main variable.

Trust comment: Randomized clinical reconstruction study with objective radiographic and histomorphometric endpoints; collagen sponge was scaffold but not randomized variable.

Study Details

PMID:24683583
Participants:40
Impact:Low-CD34 group 36% ±10% vs high-CD34 group 67% ±13% (mean ± SD)
Trust score:4/5

IKDC subjective score (overall)

1 evidences

A randomized multicentre trial (PP n=100) found the coll-HA osteochondral scaffold safe and—while overall similar to bone marrow stimulation—superior in predefined subgroups of complex osteochondral lesions.

Trust comment: Multicentre randomized trial with blinded imaging and predefined PP analysis, though underpowered vs original target and with heterogeneity; overall reasonably high quality.

Study Details

PMID:28913600
Participants:100
Impact:No significant difference at 2 years (adjusted mean difference −0.48, n.s.)
Trust score:4/5

IKDC subjective score (deep osteochondral lesions)

1 evidences

A randomized multicentre trial (PP n=100) found the coll-HA osteochondral scaffold safe and—while overall similar to bone marrow stimulation—superior in predefined subgroups of complex osteochondral lesions.

Trust comment: Multicentre randomized trial with blinded imaging and predefined PP analysis, though underpowered vs original target and with heterogeneity; overall reasonably high quality.

Study Details

PMID:28913600
Participants:100
Impact:Adjusted mean difference +12.4 points favoring coll-HA (p=0.036)
Trust score:4/5

IKDC subjective score (sport-active subgroup)

1 evidences

A randomized multicentre trial (PP n=100) found the coll-HA osteochondral scaffold safe and—while overall similar to bone marrow stimulation—superior in predefined subgroups of complex osteochondral lesions.

Trust comment: Multicentre randomized trial with blinded imaging and predefined PP analysis, though underpowered vs original target and with heterogeneity; overall reasonably high quality.

Study Details

PMID:28913600
Participants:100
Impact:+16.0 points favoring coll-HA (p=0.027); safety: more adverse events in coll-HA (3 severe vs 1) and 2 failures in coll-HA group
Trust score:4/5

wound healing and complications

1 evidences

Using a resorbable collagen membrane did not reduce horizontal bone resorption; piezosurgery showed no clinical advantage over rotative instruments and took longer.

Trust comment: Randomized split-mouth clinical trial in humans with clear outcome measures and moderate sample size.

Study Details

PMID:21745325
Participants:36
Impact:no change (no differences between test and control; p=.458 and p=1.0)
Trust score:4/5

bacteriologic eradication

1 evidences

Applying gentamicin-impregnated collagen fleeces after surgery reduced pathogen presence and postoperative perineal/sacral infections.

Trust comment: Prospective randomized multicenter human trial with clinically meaningful endpoints and statistically significant results.

Study Details

PMID:11754859
Participants:97
Impact:83.7% vs 60.4% (Genta vs control); +23.3% (P=0.013)
Trust score:4/5

postoperative perineal/sacral infection rate

1 evidences

Applying gentamicin-impregnated collagen fleeces after surgery reduced pathogen presence and postoperative perineal/sacral infections.

Trust comment: Prospective randomized multicenter human trial with clinically meaningful endpoints and statistically significant results.

Study Details

PMID:11754859
Participants:97
Impact:6.1% vs 20.8% (Genta vs control); -14.7 percentage points (P<0.05)
Trust score:4/5

local gentamicin concentration (sacral drainage)

1 evidences

Applying gentamicin-impregnated collagen fleeces after surgery reduced pathogen presence and postoperative perineal/sacral infections.

Trust comment: Prospective randomized multicenter human trial with clinically meaningful endpoints and statistically significant results.

Study Details

PMID:11754859
Participants:97
Impact:day 1 median 126.2 μg/mL; day 3 median 97.6 μg/mL
Trust score:4/5

bone area fraction (coronal)

1 evidences

Adding a resorbable collagen membrane to bovine bone graft in extraction sockets increased the fraction of new bone compared with graft alone.

Trust comment: Human comparative study with histomorphometric endpoints but small sample size limits precision.

Study Details

PMID:22577652
Participants:23
Impact:22.8% (BBM) -> 35.2% (BBM + collagen membrane); +12.4 percentage points (P<.05)
Trust score:4/5

bone area fraction (apical)

1 evidences

Adding a resorbable collagen membrane to bovine bone graft in extraction sockets increased the fraction of new bone compared with graft alone.

Trust comment: Human comparative study with histomorphometric endpoints but small sample size limits precision.

Study Details

PMID:22577652
Participants:23
Impact:36.3% (BBM) -> 47.0% (BBM + collagen membrane); +10.7 percentage points (P<.05)
Trust score:4/5

overall BAF with collagen membrane

1 evidences

Adding a resorbable collagen membrane to bovine bone graft in extraction sockets increased the fraction of new bone compared with graft alone.

Trust comment: Human comparative study with histomorphometric endpoints but small sample size limits precision.

Study Details

PMID:22577652
Participants:23
Impact:significantly higher BAF across depths with membrane (P<.05)
Trust score:4/5

minor complications

2 evidences

Compared immediate implant placement versus delayed placement with socket preservation using bovine bone and a resorbable collagen barrier; immediate placement had more complications but similar aesthetics and patient satisfaction.

Trust comment: Pragmatic multicentre RCT with blinded assessors and complete 4-month follow-up, moderate sample size and clinically relevant endpoints.

Study Details

PMID:22282730
Participants:106
Impact:Immediate group 8 vs delayed group 1 (P = 0.032)
Trust score:4/5

Randomized multicenter trial comparing immediate post-extractive implants vs delayed implants (delayed group received socket preservation with bovine bone and a resorbable collagen barrier); aesthetics similar, more complications with immediate implants.

Trust comment: Multicenter randomized trial with blinded assessors and 1-year follow-up; collagen membrane was used in the delayed (socket preservation) arm but not isolated as a single factor.

Study Details

PMID:26669545
Participants:106
Impact:Immediate 8 events vs Delayed 1 event (P=0.028)
Trust score:4/5

aesthetic score (PES)

1 evidences

Compared immediate implant placement versus delayed placement with socket preservation using bovine bone and a resorbable collagen barrier; immediate placement had more complications but similar aesthetics and patient satisfaction.

Trust comment: Pragmatic multicentre RCT with blinded assessors and complete 4-month follow-up, moderate sample size and clinically relevant endpoints.

Study Details

PMID:22282730
Participants:106
Impact:no significant difference (12.8 vs 12.6; P = 0.5)
Trust score:4/5

vessel occlusion rates

1 evidences

Compared collagen-coated polyester patch closure versus direct closure in carotid surgery and found no significant differences in vessel occlusion, morbidity, or mortality at 12 months.

Trust comment: Large randomized trial with over 300 procedures and 12-month follow-up; good quality for surgical device outcomes.

Study Details

PMID:17038946
Participants:315
Impact:no significant difference at 12 months (patched 5/146 vs direct 3/167)
Trust score:4/5

Morbidity/mortality

1 evidences

Compared collagen-coated polyester patch closure versus direct closure in carotid surgery and found no significant differences in vessel occlusion, morbidity, or mortality at 12 months.

Trust comment: Large randomized trial with over 300 procedures and 12-month follow-up; good quality for surgical device outcomes.

Study Details

PMID:17038946
Participants:315
Impact:no significant difference between groups
Trust score:4/5

vessel patency/clinical outcome

1 evidences

Compared collagen-coated polyester patch closure versus direct closure in carotid surgery and found no significant differences in vessel occlusion, morbidity, or mortality at 12 months.

Trust comment: Large randomized trial with over 300 procedures and 12-month follow-up; good quality for surgical device outcomes.

Study Details

PMID:17038946
Participants:315
Impact:no difference identified
Trust score:4/5

gingival recession (GR)

1 evidences

12-month RCT (51 subjects) showed guided tissue regeneration with collagen membrane improved probing depth and clinical attachment versus open flap debridement, but collagen membrane increased gingival recession compared with other treatments.

Trust comment: Randomized controlled clinical trial directly testing a collagen membrane vs alternatives with 12-month follow-up; moderate-high quality evidence.

Study Details

PMID:18834243
Participants:51
Impact:CM showed significantly greater increase in GR vs OFD and CS
Trust score:4/5

serum collagen synthesis markers

1 evidences

Postoperative oral prednisolone lowered serum markers of collagen synthesis systemically but did not improve surgical success of Molteno implantation over 6 months.

Trust comment: Randomized clinical trial in humans but small sample and clinical endpoint differences were not statistically significant.

Study Details

PMID:10071149
Participants:22
Impact:statistically significant decrease in prednisolone group
Trust score:3/5

pain (WOMAC/VAS)

1 evidences

Undenatured chicken type II collagen (Artneo) taken daily for 180 days reduced pain and stiffness and improved joint function and quality of life versus placebo in knee OA.

Trust comment: Multicenter, double-blind, placebo-controlled RCT with adequate sample size (n=212); good design and reported superiority to placebo.

Study Details

PMID:38829812
Participants:212
Impact:reduced vs placebo (statistically significant)
Trust score:4/5

stiffness and joint function (WOMAC/KOOS)

1 evidences

Undenatured chicken type II collagen (Artneo) taken daily for 180 days reduced pain and stiffness and improved joint function and quality of life versus placebo in knee OA.

Trust comment: Multicenter, double-blind, placebo-controlled RCT with adequate sample size (n=212); good design and reported superiority to placebo.

Study Details

PMID:38829812
Participants:212
Impact:improved vs placebo (statistically significant)
Trust score:4/5

quality of life (EQ-5D)

1 evidences

Undenatured chicken type II collagen (Artneo) taken daily for 180 days reduced pain and stiffness and improved joint function and quality of life versus placebo in knee OA.

Trust comment: Multicenter, double-blind, placebo-controlled RCT with adequate sample size (n=212); good design and reported superiority to placebo.

Study Details

PMID:38829812
Participants:212
Impact:improved vs placebo (statistically significant)
Trust score:4/5

combined clinical-radiographic healing rate

1 evidences

PRP, PRP plus collagen sponge, and collagen membrane yielded similar high healing rates for apicomarginal defects over 1 year.

Trust comment: Randomized clinical study in humans with moderate sample size (n=30); small groups limit precision but design and outcomes are clinically relevant.

Study Details

PMID:21787487
Participants:30
Impact:PRP 83.33%, PRP+collagen sponge 88.89%, collagen membrane 80% (healing rates)
Trust score:3/5

periodontal support and probing depth reduction

1 evidences

PRP, PRP plus collagen sponge, and collagen membrane yielded similar high healing rates for apicomarginal defects over 1 year.

Trust comment: Randomized clinical study in humans with moderate sample size (n=30); small groups limit precision but design and outcomes are clinically relevant.

Study Details

PMID:21787487
Participants:30
Impact:improvements observed in all groups with no clear differences between treatments
Trust score:3/5

relative attachment gain

1 evidences

Randomized allocation of 30 defects in 25 patients to graft alone, graft+PRP, and graft+PRP+membrane; all treatments improved clinical measures similarly with no added clinical benefit from PRP.

Trust comment: Small randomized allocation by defect with objective measures but limited sample size and defect-based randomization.

Study Details

PMID:17470012
Participants:25
Impact:~2.1–2.5 mm gain at 12 months (2.4, 2.1, 2.5 mm) with no significant between-group differences
Trust score:3/5

type I collagen production

1 evidences

In women undergoing abdominoplasty, PRP and nanofat injections increased type I collagen in stretch-mark tissue; combined PRP+nanofat produced the largest increase and better clinical improvement.

Trust comment: Prospective randomized single-blind trial with biopsy quantification (moderate quality), directly measures collagen production.

Study Details

PMID:39627329
Participants:50
Impact:increased (combined PRP+nanofat > PRP or nanofat alone; p < 0.0001)
Trust score:3/5

clinical improvement of striae

1 evidences

In women undergoing abdominoplasty, PRP and nanofat injections increased type I collagen in stretch-mark tissue; combined PRP+nanofat produced the largest increase and better clinical improvement.

Trust comment: Prospective randomized single-blind trial with biopsy quantification (moderate quality), directly measures collagen production.

Study Details

PMID:39627329
Participants:50
Impact:greater improvement with combined PRP+nanofat (p = 0.001)
Trust score:3/5

skin wrinkle severity

1 evidences

PCA increased type I collagen synthesis in vitro and, in a 8-week lotion trial in women, significantly reduced facial wrinkle measures.

Trust comment: Placebo-controlled human skin trial with objective in vitro and ex vivo measures; small sample but direct collagen-related outcomes.

Study Details

PMID:31389672
Participants:22
Impact:decreased (significant reduction in wrinkle parameters after 8 weeks)
Trust score:3/5

MMP-1 secretion

1 evidences

PCA increased type I collagen synthesis in vitro and, in a 8-week lotion trial in women, significantly reduced facial wrinkle measures.

Trust comment: Placebo-controlled human skin trial with objective in vitro and ex vivo measures; small sample but direct collagen-related outcomes.

Study Details

PMID:31389672
Participants:22
Impact:decreased (inhibition in UVA-irradiated fibroblasts)
Trust score:3/5

defect bone level (DBL) gain

1 evidences

In periodontal defects, GTR using collagen membranes and autogenous periosteal+bone chip treatment both improved probing depth, attachment level, and bone defect fill more than debridement alone; autogenous periosteal approach gave greatest bone gain.

Trust comment: Randomized controlled clinical trial with objective surgical re-entry measurements and clear numerical outcomes; directly evaluates collagen membranes.

Study Details

PMID:20583915
Participants:42
Impact:GTR: 2.4 mm; aCPRT: 3.1 mm; OFD: 1.5 mm (1 year)
Trust score:4/5

complications

2 evidences

Randomized trial (78 enrolled, 8 excluded/dropouts = 70 completed) comparing internal socket grafting alone versus with additional buccal augmentation covered by collagen resorbable membranes; no significant differences at 6 months.

Trust comment: Multicenter randomized controlled trial with blinded assessors and reported outcomes; modest sample and short-term follow-up but directly uses collagen membranes as part of the intervention.

Study Details

PMID:24179978
Participants:70
Impact:no significant difference (4 total; 2 vs 2)
Trust score:4/5

Randomized trial in ischemic foot wounds showed a collagen-based tissue-engineered skin graft substantially improved and accelerated wound healing versus moist dressings.

Trust comment: Randomized human trial of a collagen-containing (type I bovine collagen matrix) graft with clear clinical endpoints and significant effects, though sample size is small.

Study Details

PMID:10629263
Participants:31
Impact:Three localized indolent wound infections in graft group; no other significant complications reported
Trust score:4/5

implant/prosthetic failures

1 evidences

22 patients received vertical bone augmentation with either resorbable collagen barriers or nonresorbable barriers; both showed minimal and similar bone loss at 3 years.

Trust comment: Randomized controlled trial with blinded assessors and 3-year follow-up but small sample size (n=22).

Study Details

PMID:20657877
Participants:22
Impact:No implant or prosthetic failures reported after loading
Trust score:4/5

maintenance of regenerated bone

1 evidences

22 patients received vertical bone augmentation with either resorbable collagen barriers or nonresorbable barriers; both showed minimal and similar bone loss at 3 years.

Trust comment: Randomized controlled trial with blinded assessors and 3-year follow-up but small sample size (n=22).

Study Details

PMID:20657877
Participants:22
Impact:Vertically regenerated bone successfully maintained up to 3 years
Trust score:4/5

time to complete closure

1 evidences

Multicenter randomized trial comparing a living skin-equivalent (Graftskin, a collagen-containing product) versus moist gauze for chronic diabetic foot ulcers; assessed healing at 12 weeks.

Trust comment: Randomized multicenter clinical trial with intention-to-treat analysis showing significant benefit; product contains collagen matrix so findings are relevant to collagen-based therapy.

Study Details

PMID:11213881
Participants:208
Impact:−25 days median (65 days Graftskin vs 90 days control; P=0.0026)
Trust score:4/5

serious complications (osteomyelitis, amputations)

1 evidences

Multicenter randomized trial comparing a living skin-equivalent (Graftskin, a collagen-containing product) versus moist gauze for chronic diabetic foot ulcers; assessed healing at 12 weeks.

Trust comment: Randomized multicenter clinical trial with intention-to-treat analysis showing significant benefit; product contains collagen matrix so findings are relevant to collagen-based therapy.

Study Details

PMID:11213881
Participants:208
Impact:reduced incidence in Graftskin group (no numeric detail provided)
Trust score:4/5

PTH (parathyroid hormone)

1 evidences

In people with relapsing-remitting MS, weekly high-dose vitamin D raised vitamin D levels but did not meaningfully change common blood markers of bone formation or resorption over 96 weeks.

Trust comment: Randomized controlled trial in humans with 68 completers and appropriate marker measurements; limited size reduces sensitivity to small effects.

Study Details

PMID:28376767
Participants:68
Impact:Decreased (~−13.7% at 48w; −10.9% at 96w; p>0.05)
Trust score:4/5

retear rate

1 evidences

Adding a 3D collagen graft to rotator cuff repair reduced tendon retears and improved shoulder scores at 12 months; final-function differences were not significant at longest follow-up.

Trust comment: Randomized controlled trial with ~2-year follow-up and objective imaging/histology supports moderate-high trustworthiness.

Study Details

PMID:29533674
Participants:104
Impact:-20.3 percentage points (34.0% → 13.7%; P = .02)
Trust score:4/5

UCLA shoulder score (12 months)

1 evidences

Adding a 3D collagen graft to rotator cuff repair reduced tendon retears and improved shoulder scores at 12 months; final-function differences were not significant at longest follow-up.

Trust comment: Randomized controlled trial with ~2-year follow-up and objective imaging/histology supports moderate-high trustworthiness.

Study Details

PMID:29533674
Participants:104
Impact:+1.2 points (26.9 → 28.1; P = .002)
Trust score:4/5

Constant score (12 months)

1 evidences

Adding a 3D collagen graft to rotator cuff repair reduced tendon retears and improved shoulder scores at 12 months; final-function differences were not significant at longest follow-up.

Trust comment: Randomized controlled trial with ~2-year follow-up and objective imaging/histology supports moderate-high trustworthiness.

Study Details

PMID:29533674
Participants:104
Impact:+2.2 points (84.9 → 87.1; P = .003)
Trust score:4/5

serum CTX (C-terminal telopeptide)

1 evidences

In postmenopausal volunteers with low vitamin D, oral calcium produced marked suppression of bone resorption marker CTX (greater than vitamin D alone); vitamin D alone raised serum 25OHD but had smaller CTX effects.

Trust comment: Small randomized crossover human study with clear biomarker measurements but limited sample size.

Study Details

PMID:20349229
Participants:22
Impact:major suppression by calcium; threefold greater suppression with calcium versus vitamin D (P < 0.001)
Trust score:3/5

serum 25OHD

2 evidences

In postmenopausal volunteers with low vitamin D, oral calcium produced marked suppression of bone resorption marker CTX (greater than vitamin D alone); vitamin D alone raised serum 25OHD but had smaller CTX effects.

Trust comment: Small randomized crossover human study with clear biomarker measurements but limited sample size.

Study Details

PMID:20349229
Participants:22
Impact:increased by vitamin D and further elevated by calcium co-administration
Trust score:3/5

In adults with knee pain, a multi‑component supplement containing glucosamine, chondroitin, quercetin, imidazole peptides and 200 IU vitamin D increased serum 25‑OHD and improved some measures of locomotor function versus placebo over 16 weeks.

Trust comment: Well-designed randomized double-blind RCT, but the product contained multiple active ingredients (including collagen peptides), so effects cannot be attributed to collagen alone.

Study Details

PMID:26604721
Participants:82
Impact:greater increase in GCQID: +11.9 ng/mL vs placebo +6.9 ng/mL change at week 16 (difference ≈+5.0 ng/mL; p<0.05)
Trust score:4/5

bone resorption (CTX)

1 evidences

Pregnant women in an individualized high-dairy-protein diet plus walking program had higher dietary calcium and protein intakes which was associated with reduced bone resorption and preserved bone formation during pregnancy and postpartum.

Trust comment: Large randomized controlled trial with good follow-up and validated biomarker assays supports moderate-high trust.

Study Details

PMID:35759368
Participants:187
Impact:minimized/reduced in intervention versus control (protects against pregnancy-related bone loss)
Trust score:4/5

bone formation (P1NP)

1 evidences

Pregnant women in an individualized high-dairy-protein diet plus walking program had higher dietary calcium and protein intakes which was associated with reduced bone resorption and preserved bone formation during pregnancy and postpartum.

Trust comment: Large randomized controlled trial with good follow-up and validated biomarker assays supports moderate-high trust.

Study Details

PMID:35759368
Participants:187
Impact:maintained (no decline compared with control)
Trust score:4/5

IGF-1

2 evidences

Four-month randomized double-blind trial in prepubertal children found daily hydrolyzed collagen (with or without added calcium) increased markers related to bone modeling—most notably IGF-1 and alkaline phosphatase when collagen was given with calcium.

Trust comment: Randomized double-blind trial in children with clear biomarker changes, but moderate sample size and short duration limit strength of conclusions.

Study Details

PMID:21648282
Participants:60
Impact:Greater increase in collagen+calcium group (G-III) vs collagen alone (G-II) and placebo (G-I); significant (p<0.01 vs G-II; p<0.05 vs G-I)
Trust score:4/5

Pregnant women in an individualized high-dairy-protein diet plus walking program had higher dietary calcium and protein intakes which was associated with reduced bone resorption and preserved bone formation during pregnancy and postpartum.

Trust comment: Large randomized controlled trial with good follow-up and validated biomarker assays supports moderate-high trust.

Study Details

PMID:35759368
Participants:187
Impact:measured as a related biomarker (no large adverse change reported)
Trust score:4/5

membrane exposure incidence

1 evidences

In guided bone regeneration, early membrane exposure occurred in 10 of 29 sites; incision location and palatal/lingual gingival thickness influenced flap survival and membrane exposure, with collagen membranes among the tested materials.

Trust comment: Prospective human study with small sample and site-level outcomes; relevant to collagen membrane performance but limited size.

Study Details

PMID:17199538
Participants:25
Impact:10 of 29 sites experienced early exposure (exposed sites that remained exposed at 1 month stayed exposed)
Trust score:3/5

flap survival length

1 evidences

In guided bone regeneration, early membrane exposure occurred in 10 of 29 sites; incision location and palatal/lingual gingival thickness influenced flap survival and membrane exposure, with collagen membranes among the tested materials.

Trust comment: Prospective human study with small sample and site-level outcomes; relevant to collagen membrane performance but limited size.

Study Details

PMID:17199538
Participants:25
Impact:no significant difference between membrane-treated groups and adjacent KG width; graft-alone group had greater survival beyond KG (1.6 ± 0.4 mm; P = 0.002)
Trust score:3/5

palatal/lingual gingival thickness

1 evidences

In guided bone regeneration, early membrane exposure occurred in 10 of 29 sites; incision location and palatal/lingual gingival thickness influenced flap survival and membrane exposure, with collagen membranes among the tested materials.

Trust comment: Prospective human study with small sample and site-level outcomes; relevant to collagen membrane performance but limited size.

Study Details

PMID:17199538
Participants:25
Impact:thinner palatal/lingual gingiva associated with higher exposure risk (P = 0.002)
Trust score:3/5

baseline CTX-I

1 evidences

In a biomarker subgroup of a randomized trial, higher baseline CTX-I (a type I collagen breakdown marker) predicted greater likelihood of clinical remission/response to abatacept+MTX, and abatacept+MTX produced greater reductions in several ECM/collagen-related biomarkers versus placebo+MTX.

Trust comment: Post-hoc biomarker analysis of a large randomized trial with robust assays; predictive findings are exploratory and need prospective validation.

Study Details

PMID:36585217
Participants:535
Impact:higher baseline CTX-I associated with increased probability of SDAI remission and DAS28(CRP)<2.6 at weeks 24 and 52 (statistically significant predictive effect)
Trust score:4/5

ECM biomarkers (C3M, C4M, CRPM, RANKL)

1 evidences

In a biomarker subgroup of a randomized trial, higher baseline CTX-I (a type I collagen breakdown marker) predicted greater likelihood of clinical remission/response to abatacept+MTX, and abatacept+MTX produced greater reductions in several ECM/collagen-related biomarkers versus placebo+MTX.

Trust comment: Post-hoc biomarker analysis of a large randomized trial with robust assays; predictive findings are exploratory and need prospective validation.

Study Details

PMID:36585217
Participants:535
Impact:greater reductions with abatacept+MTX versus abatacept placebo+MTX at weeks 24 and 52 (p<0.01 for many markers)
Trust score:4/5

ACR70 response

1 evidences

In a biomarker subgroup of a randomized trial, higher baseline CTX-I (a type I collagen breakdown marker) predicted greater likelihood of clinical remission/response to abatacept+MTX, and abatacept+MTX produced greater reductions in several ECM/collagen-related biomarkers versus placebo+MTX.

Trust comment: Post-hoc biomarker analysis of a large randomized trial with robust assays; predictive findings are exploratory and need prospective validation.

Study Details

PMID:36585217
Participants:535
Impact:greater likelihood in patients with medium/high baseline CTX-I receiving abatacept+MTX
Trust score:4/5

aqueous ofloxacin concentration

1 evidences

A collagen shield presoaked with ofloxacin produced higher anterior chamber antibiotic concentrations than topical drops before cataract surgery.

Trust comment: Randomized clinical study directly testing a collagen-based device (collagen shield) in humans but small sample size.

Study Details

PMID:10198864
Participants:31
Impact:Mean 287 ng/mL (drops) vs 957 ng/mL (collagen shield); P<.005
Trust score:3/5

proportion reaching MIC range

1 evidences

A collagen shield presoaked with ofloxacin produced higher anterior chamber antibiotic concentrations than topical drops before cataract surgery.

Trust comment: Randomized clinical study directly testing a collagen-based device (collagen shield) in humans but small sample size.

Study Details

PMID:10198864
Participants:31
Impact:Collagen shield reached or exceeded MICs for many ocular pathogens (MIC range reported 500–4000 ng/mL)
Trust score:3/5

facial wrinkles

1 evidences

In ~82 women >40, 24 weeks of the herbal mixture improved facial wrinkles and increased type I procollagen expression in skin compared with placebo.

Trust comment: Randomized double‑blind placebo‑controlled trial with 82 completers and objective biochemical and histologic endpoints; reporting lacks numeric effect sizes for some outcomes.

Study Details

PMID:20041778
Participants:82
Impact:clinically improved (statistically significant vs placebo)
Trust score:4/5

type I procollagen expression

1 evidences

In ~82 women >40, 24 weeks of the herbal mixture improved facial wrinkles and increased type I procollagen expression in skin compared with placebo.

Trust comment: Randomized double‑blind placebo‑controlled trial with 82 completers and objective biochemical and histologic endpoints; reporting lacks numeric effect sizes for some outcomes.

Study Details

PMID:20041778
Participants:82
Impact:increased (gene and protein expression) in treatment group
Trust score:4/5

MMP-9 induction

1 evidences

In ~82 women >40, 24 weeks of the herbal mixture improved facial wrinkles and increased type I procollagen expression in skin compared with placebo.

Trust comment: Randomized double‑blind placebo‑controlled trial with 82 completers and objective biochemical and histologic endpoints; reporting lacks numeric effect sizes for some outcomes.

Study Details

PMID:20041778
Participants:82
Impact:prevention of MMP-9 induction (treatment vs placebo)
Trust score:4/5

lumbar spine BMD (difference denosumab vs risedronate)

1 evidences

Denosumab increased bone mineral density more than risedronate over 24 months; all participants received daily calcium and vitamin D as background therapy.

Trust comment: Large, international, double‑blind, randomized active‑controlled phase III trial with centralized BMD and marker analyses; high methodological quality.

Study Details

PMID:30816640
Participants:590
Impact:+4.5% (glucocorticoid‑initiating subpopulation, baseline to month 24) and +3.2% (continuing subpopulation)
Trust score:5/5

total hip BMD (difference denosumab vs risedronate)

1 evidences

Denosumab increased bone mineral density more than risedronate over 24 months; all participants received daily calcium and vitamin D as background therapy.

Trust comment: Large, international, double‑blind, randomized active‑controlled phase III trial with centralized BMD and marker analyses; high methodological quality.

Study Details

PMID:30816640
Participants:590
Impact:+3.1% (initiating) and +2.5% (continuing) at 24 months
Trust score:5/5

CTX (C‑telopeptide of type I collagen)

1 evidences

Denosumab increased bone mineral density more than risedronate over 24 months; all participants received daily calcium and vitamin D as background therapy.

Trust comment: Large, international, double‑blind, randomized active‑controlled phase III trial with centralized BMD and marker analyses; high methodological quality.

Study Details

PMID:30816640
Participants:590
Impact:greater reduction with denosumab vs risedronate from day 10 to month 12; differences not significant by month 24
Trust score:5/5

sCD163 (macrophage activation)

1 evidences

In 54 patients with decompensated cirrhosis, 28 days of rifaximin‑α produced no significant changes in macrophage activation markers or neoepitope collagen remodeling markers compared with placebo.

Trust comment: Randomized double‑blind placebo‑controlled trial with specific biomarker assays; modest sample size (n=54) and short treatment duration limit detection of small effects.

Study Details

PMID:30183743
Participants:54
Impact:no significant change (p=0.34)
Trust score:4/5

sMR (mannose receptor)

1 evidences

In 54 patients with decompensated cirrhosis, 28 days of rifaximin‑α produced no significant changes in macrophage activation markers or neoepitope collagen remodeling markers compared with placebo.

Trust comment: Randomized double‑blind placebo‑controlled trial with specific biomarker assays; modest sample size (n=54) and short treatment duration limit detection of small effects.

Study Details

PMID:30183743
Participants:54
Impact:no significant change (p=0.34)
Trust score:4/5

PRO-C3 (type III collagen formation)

1 evidences

In 54 patients with decompensated cirrhosis, 28 days of rifaximin‑α produced no significant changes in macrophage activation markers or neoepitope collagen remodeling markers compared with placebo.

Trust comment: Randomized double‑blind placebo‑controlled trial with specific biomarker assays; modest sample size (n=54) and short treatment duration limit detection of small effects.

Study Details

PMID:30183743
Participants:54
Impact:no significant change vs placebo after 28 days
Trust score:4/5

BPBM + collagen membrane outcome

1 evidences

In 45 patients with bilateral impacted lower third molars, use of bovine porous bone mineral with or without a collagen membrane reduced pocket depth and gained attachment versus untreated controls over long follow‑up.

Trust comment: Randomized assignment, long follow‑up (up to 72 months) and clinically meaningful endpoints support reasonable trust, though sample size moderate (45 patients, 90 sites).

Study Details

PMID:19254122
Participants:45
Impact:best prevention of second‑molar periodontal defect (superior outcome)
Trust score:4/5

C-telopeptide of type I collagen (CTX)

1 evidences

Randomized trial of neridronate vs control in thalassaemia-associated osteoporosis; both groups received calcium + 400 IU vitamin D daily; neridronate increased BMD and reduced bone turnover and back pain.

Trust comment: Randomized phase 2 trial with clear clinical endpoints and 118 participants; open-label design lowers blinding robustness but results are plausible and reported with statistics.

Study Details

PMID:22571408
Participants:118
Impact:decrease (significant from 3 months; lower at 12 months vs control)
Trust score:4/5

total mineralized bone area

1 evidences

Randomized clinical comparison found the new collagen barrier membrane produced similar histologic bone regeneration to standard e-PTFE membrane.

Trust comment: Randomized clinical study with histomorphometric endpoints but modest sample size (pilot), limiting generalizability.

Study Details

PMID:12519332
Participants:28
Impact:Ossix (collagen) 42% ± 18% vs PTFE 39% ± 15% (no significant difference)
Trust score:3/5

unmineralized tissue area

1 evidences

Randomized clinical comparison found the new collagen barrier membrane produced similar histologic bone regeneration to standard e-PTFE membrane.

Trust comment: Randomized clinical study with histomorphometric endpoints but modest sample size (pilot), limiting generalizability.

Study Details

PMID:12519332
Participants:28
Impact:Ossix 44% ± 15% vs PTFE 46% ± 12% (no significant difference)
Trust score:3/5

DBBM remnants area

1 evidences

Randomized clinical comparison found the new collagen barrier membrane produced similar histologic bone regeneration to standard e-PTFE membrane.

Trust comment: Randomized clinical study with histomorphometric endpoints but modest sample size (pilot), limiting generalizability.

Study Details

PMID:12519332
Participants:28
Impact:Ossix 14% ± 9% vs PTFE 15% ± 12% (no significant difference)
Trust score:3/5

type I collagen telopeptide (high)

1 evidences

In post-MI patients with LV dysfunction, collagen turnover biomarkers predicted outcomes and eplerenone reduced procollagen levels over follow-up.

Trust comment: Large substudy (n=476) of a randomized trial with clinical endpoints and serial biomarker measurements—reasonably high reliability.

Study Details

PMID:19398668
Participants:476
Impact:High level with high BNP associated with higher all-cause mortality (HR 2.49) and composite CV death/HF hospitalization (HR 3.03)
Trust score:4/5

aminoterminal propeptide of type I and III procollagen

1 evidences

In post-MI patients with LV dysfunction, collagen turnover biomarkers predicted outcomes and eplerenone reduced procollagen levels over follow-up.

Trust comment: Large substudy (n=476) of a randomized trial with clinical endpoints and serial biomarker measurements—reasonably high reliability.

Study Details

PMID:19398668
Participants:476
Impact:Levels consistently lower in eplerenone group, significantly lower beginning at 6 months
Trust score:4/5

total alkaline phosphatase (tALP)

1 evidences

Four-month randomized double-blind trial in prepubertal children found daily hydrolyzed collagen (with or without added calcium) increased markers related to bone modeling—most notably IGF-1 and alkaline phosphatase when collagen was given with calcium.

Trust comment: Randomized double-blind trial in children with clear biomarker changes, but moderate sample size and short duration limit strength of conclusions.

Study Details

PMID:21648282
Participants:60
Impact:Greater increase in collagen+calcium group (G-III) vs placebo (G-I) (p<0.05)
Trust score:4/5

bone alkaline phosphatase (bALP)

1 evidences

Four-month randomized double-blind trial in prepubertal children found daily hydrolyzed collagen (with or without added calcium) increased markers related to bone modeling—most notably IGF-1 and alkaline phosphatase when collagen was given with calcium.

Trust comment: Randomized double-blind trial in children with clear biomarker changes, but moderate sample size and short duration limit strength of conclusions.

Study Details

PMID:21648282
Participants:60
Impact:Behavior differed: increase in collagen alone (G-II) vs decrease in placebo (G-I) (p<0.05)
Trust score:4/5

tartrate-resistant acid phosphatase (TRAP)

1 evidences

Four-month randomized double-blind trial in prepubertal children found daily hydrolyzed collagen (with or without added calcium) increased markers related to bone modeling—most notably IGF-1 and alkaline phosphatase when collagen was given with calcium.

Trust comment: Randomized double-blind trial in children with clear biomarker changes, but moderate sample size and short duration limit strength of conclusions.

Study Details

PMID:21648282
Participants:60
Impact:Significant group differences across treatments (G-II vs G-I p<0.01; G-III vs G-II p<0.05)
Trust score:4/5

seroma incidence

1 evidences

Compared two acellular dermal matrix products in bilateral breast reconstruction; AlloDerm had more seromas and slightly lower incorporation than DermACELL.

Trust comment: Prospective, patient-blind within-patient randomized design with clear outcome measures; moderate sample size supports reliability.

Study Details

PMID:38377366
Participants:55
Impact:AlloDerm 30.91% vs DermACELL 14.55% (AlloDerm +16.36 percentage points, P<0.05)
Trust score:4/5

incorporation rate

1 evidences

Compared two acellular dermal matrix products in bilateral breast reconstruction; AlloDerm had more seromas and slightly lower incorporation than DermACELL.

Trust comment: Prospective, patient-blind within-patient randomized design with clear outcome measures; moderate sample size supports reliability.

Study Details

PMID:38377366
Participants:55
Impact:AlloDerm 93.4% vs DermACELL 99.8% (AlloDerm −6.4 percentage points, P<0.05)
Trust score:4/5

reconstruction success rate

1 evidences

Compared two acellular dermal matrix products in bilateral breast reconstruction; AlloDerm had more seromas and slightly lower incorporation than DermACELL.

Trust comment: Prospective, patient-blind within-patient randomized design with clear outcome measures; moderate sample size supports reliability.

Study Details

PMID:38377366
Participants:55
Impact:Both products 94.55% (no difference)
Trust score:4/5

horizontal ridge resorption

1 evidences

Ridge preservation using corticocancellous porcine bone plus a collagen membrane significantly limited horizontal and vertical ridge resorption and increased mineralized bone versus extraction alone after 7 months.

Trust comment: Randomized clinical trial with histomorphometric endpoints and clear numerical outcomes; moderate sample size gives reasonable confidence.

Study Details

PMID:18672985
Participants:40
Impact:Extraction alone 4.3±0.8 mm vs ridge-preservation 2.5±1.2 mm (RP reduced resorption by ~1.8 mm)
Trust score:4/5

buccal ridge height reduction

1 evidences

Ridge preservation using corticocancellous porcine bone plus a collagen membrane significantly limited horizontal and vertical ridge resorption and increased mineralized bone versus extraction alone after 7 months.

Trust comment: Randomized clinical trial with histomorphometric endpoints and clear numerical outcomes; moderate sample size gives reasonable confidence.

Study Details

PMID:18672985
Participants:40
Impact:Extraction alone 3.6±1.5 mm vs RP 0.7±1.4 mm (RP ~2.9 mm less loss)
Trust score:4/5

mineralized bone / trabecular bone percentage

1 evidences

Ridge preservation using corticocancellous porcine bone plus a collagen membrane significantly limited horizontal and vertical ridge resorption and increased mineralized bone versus extraction alone after 7 months.

Trust comment: Randomized clinical trial with histomorphometric endpoints and clear numerical outcomes; moderate sample size gives reasonable confidence.

Study Details

PMID:18672985
Participants:40
Impact:Higher percentage of trabecular bone and total mineralized tissue in grafted (RP) sites vs extraction-alone at 7 months (significant)
Trust score:4/5

reduction in bleeding on probing

1 evidences

In combined surgical therapy of peri-implantitis with bone graft and collagen membrane, the choice of debridement/decontamination method (Er:YAG laser vs curets+saline) did not significantly affect 6-month clinical or radiographic outcomes.

Trust comment: Randomized controlled clinical study on humans with objective clinical and radiographic measures, but small sample and short follow-up limit generalizability.

Study Details

PMID:21219392
Participants:30
Impact:No significant difference between ERL (47.8±35.5%) and CPS (55.0±31.1%) at 6 months
Trust score:4/5

Type I procollagen (procollagen I)

1 evidences

Among abstinent smokers who completed the protocol (n=39), 10 days of transdermal nicotine increased type I procollagen levels compared with placebo.

Trust comment: Human randomized, double-blind study with modest sample (39 completers) and short duration; outcome directly measures collagen synthesis.

Study Details

PMID:16808802
Participants:39
Impact:+18% with nicotine patch vs −10% with placebo during abstinence (p<0.05)
Trust score:3/5

Hydroxyproline deposition

1 evidences

Among abstinent smokers who completed the protocol (n=39), 10 days of transdermal nicotine increased type I procollagen levels compared with placebo.

Trust comment: Human randomized, double-blind study with modest sample (39 completers) and short duration; outcome directly measures collagen synthesis.

Study Details

PMID:16808802
Participants:39
Impact:No change with abstinence or nicotine vs smoking/placebo
Trust score:3/5

Procollagen type 1 N-terminal propeptide (P1NP)

1 evidences

In 833 glucocorticoid-treated patients, annual zoledronic acid reduced bone turnover markers more than daily risedronate over 12 months.

Trust comment: Large randomized study with clear biochemical endpoints and appropriate stratification; results robust for bone turnover markers.

Study Details

PMID:23365149
Participants:833
Impact:greater reductions with zoledronic acid vs risedronate (P < 0.05)
Trust score:4/5

change in bone height

1 evidences

Multicenter randomized trial found rhBMP-2 on an absorbable collagen sponge produced substantial new bone and comparable implant outcomes to autograft, with less donor-site morbidity.

Trust comment: Large multicenter randomized clinical trial using an absorbable collagen sponge as BMP carrier—good design and sample size, directly relevant to a collagen-based medical device though not oral collagen supplementation.

Study Details

PMID:19686934
Participants:160
Impact:rhBMP-2/ACS mean +7.83 ±3.52 mm vs autograft +9.46 ±4.11 mm at 6 months
Trust score:4/5

induced bone density

1 evidences

Multicenter randomized trial found rhBMP-2 on an absorbable collagen sponge produced substantial new bone and comparable implant outcomes to autograft, with less donor-site morbidity.

Trust comment: Large multicenter randomized clinical trial using an absorbable collagen sponge as BMP carrier—good design and sample size, directly relevant to a collagen-based medical device though not oral collagen supplementation.

Study Details

PMID:19686934
Participants:160
Impact:rhBMP-2/ACS induced bone denser than autograft at 6 months (significant)
Trust score:4/5

implant integration / success rate

1 evidences

Multicenter randomized trial found rhBMP-2 on an absorbable collagen sponge produced substantial new bone and comparable implant outcomes to autograft, with less donor-site morbidity.

Trust comment: Large multicenter randomized clinical trial using an absorbable collagen sponge as BMP carrier—good design and sample size, directly relevant to a collagen-based medical device though not oral collagen supplementation.

Study Details

PMID:19686934
Participants:160
Impact:rhBMP-2/ACS success 79% (64/81 subjects); implants integrated: 199/241 (rhBMP-2/ACS) vs 201/251 (autograft) at 6 months after loading
Trust score:4/5

Tumor COL4A3 expression

1 evidences

In advanced NSCLC, higher tumor COL4A3 mRNA expression was associated with shorter overall survival after cisplatin–gemcitabine chemotherapy.

Trust comment: Human observational study showing an association between a collagen gene (COL4A3) and outcomes; moderate quality but limited by small sample size and retrospective tumor marker analysis.

Study Details

PMID:23108892
Participants:58
Impact:high expression associated with poorer median overall survival (significant prognostic factor)
Trust score:3/5

Treatment response rate

1 evidences

In advanced NSCLC, higher tumor COL4A3 mRNA expression was associated with shorter overall survival after cisplatin–gemcitabine chemotherapy.

Trust comment: Human observational study showing an association between a collagen gene (COL4A3) and outcomes; moderate quality but limited by small sample size and retrospective tumor marker analysis.

Study Details

PMID:23108892
Participants:58
Impact:no significant association between COL4A3 level and response rate
Trust score:3/5

Prognosis (multivariable analysis)

1 evidences

In advanced NSCLC, higher tumor COL4A3 mRNA expression was associated with shorter overall survival after cisplatin–gemcitabine chemotherapy.

Trust comment: Human observational study showing an association between a collagen gene (COL4A3) and outcomes; moderate quality but limited by small sample size and retrospective tumor marker analysis.

Study Details

PMID:23108892
Participants:58
Impact:COL4A3 expression remained an independent prognostic factor for survival
Trust score:3/5

vertical bone fill (mean)

1 evidences

Randomized study comparing a synthetic PEG hydrogel membrane vs standard collagen membrane for guided bone regeneration around implants; regenerated bone was similar and both membranes performed comparably after 6 months.

Trust comment: Randomized clinical trial in humans but small sample size (n=37) and short-term (6 months); directly compares a collagen membrane as clinical control.

Study Details

PMID:19191793
Participants:37
Impact:PEG membrane: 5.63 ± 1.84 mm; collagen membrane: 4.25 ± 1.16 mm
Trust score:3/5

soft tissue complications

1 evidences

Randomized study comparing a synthetic PEG hydrogel membrane vs standard collagen membrane for guided bone regeneration around implants; regenerated bone was similar and both membranes performed comparably after 6 months.

Trust comment: Randomized clinical trial in humans but small sample size (n=37) and short-term (6 months); directly compares a collagen membrane as clinical control.

Study Details

PMID:19191793
Participants:37
Impact:more soft tissue complications observed with PEG membrane (delayed/incomplete healing)
Trust score:3/5

Ridge width reduction

1 evidences

Randomized controlled trial of socket preservation using bovine bone mineral plus porcine collagen membrane vs extraction alone; collagen membrane with graft markedly limited horizontal and vertical ridge resorption at 4 months.

Trust comment: Randomized controlled clinical trial using a collagen membrane as the intervention with histologic analysis; moderate sample size but strong design for surgical outcome.

Study Details

PMID:22577648
Participants:41
Impact:SP group 1.04 ±1.08 mm vs extraction-alone 4.48 ±0.65 mm (P < .001)
Trust score:4/5

Ridge height reduction

1 evidences

Randomized controlled trial of socket preservation using bovine bone mineral plus porcine collagen membrane vs extraction alone; collagen membrane with graft markedly limited horizontal and vertical ridge resorption at 4 months.

Trust comment: Randomized controlled clinical trial using a collagen membrane as the intervention with histologic analysis; moderate sample size but strong design for surgical outcome.

Study Details

PMID:22577648
Participants:41
Impact:SP group 0.46 ±0.46 mm vs extraction-alone 1.54 ±0.33 mm (P < .001)
Trust score:4/5

Clinical periodontal measures (PPD, CAL)

1 evidences

Randomized controlled trial of socket preservation using bovine bone mineral plus porcine collagen membrane vs extraction alone; collagen membrane with graft markedly limited horizontal and vertical ridge resorption at 4 months.

Trust comment: Randomized controlled clinical trial using a collagen membrane as the intervention with histologic analysis; moderate sample size but strong design for surgical outcome.

Study Details

PMID:22577648
Participants:41
Impact:No significant difference between groups
Trust score:4/5

Aqueous tobramycin concentration

1 evidences

Prospective randomized study comparing preoperative tobramycin-dexamethasone drops vs a pre-soaked collagen shield in cataract patients; aqueous antibiotic concentrations were similar and both below MIC, with no adverse effects from the collagen shield.

Trust comment: Randomized prospective clinical study testing a collagen-based device in humans; small sample and many unanalyzable samples reduce certainty.

Study Details

PMID:9684075
Participants:21
Impact:Drops mean 0.026 µg/mL vs collagen shield mean 0.024 µg/mL (no significant difference); both << MIC of 4 µg/mL
Trust score:3/5

Safety/adverse effects

1 evidences

Prospective randomized study comparing preoperative tobramycin-dexamethasone drops vs a pre-soaked collagen shield in cataract patients; aqueous antibiotic concentrations were similar and both below MIC, with no adverse effects from the collagen shield.

Trust comment: Randomized prospective clinical study testing a collagen-based device in humans; small sample and many unanalyzable samples reduce certainty.

Study Details

PMID:9684075
Participants:21
Impact:No adverse effects related to collagen shields observed
Trust score:3/5

Attachment gain

1 evidences

Proof-of-principle randomized study of collagen scaffolds with/without autologous BM-MSCs for periodontal defects: all treatments led to significant clinical improvements over 12 months with no adverse healing events; radiographic bone fill was less in scaffold-only group.

Trust comment: Small, randomized proof-of-principle trial using collagen scaffolds; clinically meaningful outcomes but limited sample size and defect-based randomization.

Study Details

PMID:33899259
Participants:27
Impact:+3.0 mm (estimated marginal mean at 12 months)
Trust score:3/5

Normal walking speed

1 evidences

In adults with knee pain, a multi‑component supplement containing glucosamine, chondroitin, quercetin, imidazole peptides and 200 IU vitamin D increased serum 25‑OHD and improved some measures of locomotor function versus placebo over 16 weeks.

Trust comment: Well-designed randomized double-blind RCT, but the product contained multiple active ingredients (including collagen peptides), so effects cannot be attributed to collagen alone.

Study Details

PMID:26604721
Participants:82
Impact:+0.15 m/s (1.36 vs 1.21 m/s at week 16 in K–L grade I subgroup; p<0.05)
Trust score:4/5

JKOM total score (knee function)

1 evidences

In adults with knee pain, a multi‑component supplement containing glucosamine, chondroitin, quercetin, imidazole peptides and 200 IU vitamin D increased serum 25‑OHD and improved some measures of locomotor function versus placebo over 16 weeks.

Trust comment: Well-designed randomized double-blind RCT, but the product contained multiple active ingredients (including collagen peptides), so effects cannot be attributed to collagen alone.

Study Details

PMID:26604721
Participants:82
Impact:−20.3 points vs 0.5 at week 8 in K–L ≥II subgroup (p<0.05)
Trust score:4/5

type I collagen expression

1 evidences

Eight weeks of split-face home device use improved skin-aging measures and increased type I collagen expression while decreasing MMP-1, with no adverse effects.

Trust comment: Randomized split-face clinical trial with supportive ex vivo and histology data, moderate sample size and objective endpoints.

Study Details

PMID:38236440
Participants:36
Impact:increased in skin biopsies after 8 weeks
Trust score:4/5

uTIINE concentration

1 evidences

Measured urine type II collagen neoepitope and related it to radiographic knee joint narrowing over 30 months in 120 women with unilateral knee OA.

Trust comment: Well‑characterized human cohort within an RCT sample with serial measurements but observational associations and subgroup selection limit causal inference.

Study Details

PMID:16753310
Participants:120
Impact:1‑SD increase (68 ng/mM Cr) associated with OR 2.04 for JSN progression in active treatment group (95% CI 0.98–4.28)
Trust score:3/5

Joint space narrowing (JSN)

2 evidences

Measured urine type II collagen neoepitope and related it to radiographic knee joint narrowing over 30 months in 120 women with unilateral knee OA.

Trust comment: Well‑characterized human cohort within an RCT sample with serial measurements but observational associations and subgroup selection limit causal inference.

Study Details

PMID:16753310
Participants:120
Impact:0.10 mm more JSN per 69 ng/mM Cr in concurrent mean uTIINE (P=0.008)
Trust score:3/5

Higher plasma LBP and sTLR4 were associated with worse knee OA progression and increased urinary collagen-breakdown marker over 16–18 months.

Trust comment: Large (n=431) human cohort from a clinical trial with multivariable adjustment; observational biomarker associations rather than a collagen intervention.

Study Details

PMID:30144513
Participants:431
Impact:OR 1.32–1.42 for JSN≥0.5 mm per SD higher LBP
Trust score:4/5

Procollagen type I C‑propeptide (P1CP)

1 evidences

In patients starting glucocorticoids, alfacalcidol (a vitamin D analog) increased some bone formation markers but BMD fell with alfacalcidol while it increased with alendronate over 18 months.

Trust comment: Large randomized, double‑blind clinical trial with standard biochemical and BMD endpoints; good internal validity though population limited to glucocorticoid users.

Study Details

PMID:17407214
Participants:201
Impact:P1CP increased in alfacalcidol group (significant) but not in alendronate group
Trust score:4/5

Bone mineral density (lumbar spine/total hip)

1 evidences

In patients starting glucocorticoids, alfacalcidol (a vitamin D analog) increased some bone formation markers but BMD fell with alfacalcidol while it increased with alendronate over 18 months.

Trust comment: Large randomized, double‑blind clinical trial with standard biochemical and BMD endpoints; good internal validity though population limited to glucocorticoid users.

Study Details

PMID:17407214
Participants:201
Impact:BMD decreased with alfacalcidol and increased with alendronate (P<0.001)
Trust score:4/5

Urinary CTX‑II/cr (type II collagen degradation)

1 evidences

Subgroup analysis from a large randomized trial showing strontium ranelate lowered urinary CTX‑II (cartilage collagen II degradation marker) over 3 years in postmenopausal women.

Trust comment: Large randomized, double‑blind trial subgroup with consistent, statistically robust biomarker changes over 3 years.

Study Details

PMID:17010685
Participants:2617
Impact:Approximately 15–20% lower CTX‑II/cr in strontium ranelate group versus placebo from 3 months onward (P<0.0001)
Trust score:4/5

WOMAC overall score

1 evidences

Double‑blind RCT of hydrolyzed chicken type II collagen (2.5 g/day) versus placebo in adults with joint discomfort over 8 weeks; assessed pain, stiffness, and function.

Trust comment: Randomized, double‑blind placebo‑controlled human trial with clinically relevant patient‑reported outcomes but small sample and short follow‑up.

Study Details

PMID:34371963
Participants:90
Impact:AVC‑H2: −36.9% at week 4 vs placebo −14.3% (β=−22.6, P=0.027); week 8: −48.6% vs −31.0%
Trust score:4/5

WOMAC stiffness subscore

1 evidences

Double‑blind RCT of hydrolyzed chicken type II collagen (2.5 g/day) versus placebo in adults with joint discomfort over 8 weeks; assessed pain, stiffness, and function.

Trust comment: Randomized, double‑blind placebo‑controlled human trial with clinically relevant patient‑reported outcomes but small sample and short follow‑up.

Study Details

PMID:34371963
Participants:90
Impact:AVC‑H2: −33.2% at week 4 vs placebo −4.5% (β=−28.6, P=0.022); week 8: −42.6% vs −15.7% (P=0.034)
Trust score:4/5

TGF‑β1 levels

1 evidences

Randomized study in paraquat poisoning patients testing Xuebijing plus conventional therapy versus conventional therapy; measured TGF‑β1, procollagen III peptide, and mortality.

Trust comment: Small randomized clinical study with clear biomarker and mortality outcomes but limited sample size and specificity to paraquat poisoning.

Study Details

PMID:23427393
Participants:56
Impact:Significantly lower over time in Xuebijing group versus conventional therapy (P<0.01)
Trust score:3/5

Procollagen type III peptide (PIIIP) levels

1 evidences

Randomized study in paraquat poisoning patients testing Xuebijing plus conventional therapy versus conventional therapy; measured TGF‑β1, procollagen III peptide, and mortality.

Trust comment: Small randomized clinical study with clear biomarker and mortality outcomes but limited sample size and specificity to paraquat poisoning.

Study Details

PMID:23427393
Participants:56
Impact:Significantly lower over time in Xuebijing group versus conventional therapy (P<0.01)
Trust score:3/5

1‑month mortality

1 evidences

Randomized study in paraquat poisoning patients testing Xuebijing plus conventional therapy versus conventional therapy; measured TGF‑β1, procollagen III peptide, and mortality.

Trust comment: Small randomized clinical study with clear biomarker and mortality outcomes but limited sample size and specificity to paraquat poisoning.

Study Details

PMID:23427393
Participants:56
Impact:Lower mortality in Xuebijing group versus conventional therapy (P<0.05)
Trust score:3/5

bone regeneration (radiographic highest grade)

1 evidences

Randomized trial in patients with bone defects: porous hydroxyapatite/collagen implant produced superior radiographic bone regeneration versus porous β-TCP by 18–24 weeks, with more (non-serious) adverse events.

Trust comment: Randomized controlled trial with objective radiographic endpoints and 119 analyzed patients; clear primary outcome reporting.

Study Details

PMID:26961287
Participants:119
Impact:↑ frequency of highest-grade regeneration at 18 & 24 weeks vs β-TCP (p=0.0004, 0.0254)
Trust score:4/5

early radiographic bone regeneration

1 evidences

Randomized trial in patients with bone defects: porous hydroxyapatite/collagen implant produced superior radiographic bone regeneration versus porous β-TCP by 18–24 weeks, with more (non-serious) adverse events.

Trust comment: Randomized controlled trial with objective radiographic endpoints and 119 analyzed patients; clear primary outcome reporting.

Study Details

PMID:26961287
Participants:119
Impact:Superior from 4 weeks onward (p=0.0084 at 4w to p<0.0001 at 18w)
Trust score:4/5

KOOS Pain score

1 evidences

12-week randomized double-blind pilot of a multinutrient supplement containing collagen (type II and collagen complex) showed within-group improvements in KOOS subscores and QoL, but did not significantly outperform placebo on the primary endpoint.

Trust comment: Randomized double-blind placebo-controlled pilot (n=52 completers) with validated outcomes but limited power and unequal group sizes; signals but primary endpoint not met.

Study Details

PMID:40664872
Participants:52
Impact:Verum +19.1% (p<0.001); Placebo +16.7% (p<0.01); between-group difference not significant (primary endpoint not met)
Trust score:3/5

KOOS Quality of Life

1 evidences

12-week randomized double-blind pilot of a multinutrient supplement containing collagen (type II and collagen complex) showed within-group improvements in KOOS subscores and QoL, but did not significantly outperform placebo on the primary endpoint.

Trust comment: Randomized double-blind placebo-controlled pilot (n=52 completers) with validated outcomes but limited power and unequal group sizes; signals but primary endpoint not met.

Study Details

PMID:40664872
Participants:52
Impact:Verum +27.66% (p<0.001)
Trust score:3/5

KOOS Sport/Recreation

1 evidences

12-week randomized double-blind pilot of a multinutrient supplement containing collagen (type II and collagen complex) showed within-group improvements in KOOS subscores and QoL, but did not significantly outperform placebo on the primary endpoint.

Trust comment: Randomized double-blind placebo-controlled pilot (n=52 completers) with validated outcomes but limited power and unequal group sizes; signals but primary endpoint not met.

Study Details

PMID:40664872
Participants:52
Impact:Verum +25.25% (p<0.01)
Trust score:3/5

N‑telopeptide of collagen type I (NTx)

1 evidences

Multicenter randomized comparison of yearly zoledronic acid vs weekly alendronate in ~600 postmenopausal women assessing bone turnover markers (NTx, P1NP): zoledronic acid produced a greater and faster reduction in both markers.

Trust comment: Large randomized multicenter trial with objective biochemical endpoints; open‑label design is a limitation but results are statistically robust.

Study Details

PMID:21442459
Participants:604
Impact:greater reduction with zoledronic acid vs alendronate (AUC change 0.282 vs 0.270 ng/mL; P=0.012)
Trust score:4/5

P1NP (procollagen type I N‑terminal propeptide)

2 evidences

Multicenter randomized comparison of yearly zoledronic acid vs weekly alendronate in ~600 postmenopausal women assessing bone turnover markers (NTx, P1NP): zoledronic acid produced a greater and faster reduction in both markers.

Trust comment: Large randomized multicenter trial with objective biochemical endpoints; open‑label design is a limitation but results are statistically robust.

Study Details

PMID:21442459
Participants:604
Impact:greater reduction with zoledronic acid vs alendronate (28.21 vs 25.53 ng/mL; P=0.0024)
Trust score:4/5

Short randomized trial showing rosiglitazone reduces biochemical markers of bone formation (including a procollagen marker) and decreases hip BMD in postmenopausal women.

Trust comment: Randomized, double‑blind controlled trial with clear biochemical and BMD endpoints but small sample and short duration (14 weeks).

Study Details

PMID:17264176
Participants:50
Impact:↓13% vs placebo (P<0.005)
Trust score:4/5

N-propeptide of type I collagen (PINP)

1 evidences

PTH therapy increased early collagen-formation markers and larger short-term increases predicted greater spine and hip BMD gains at 1 year.

Trust comment: Large randomized placebo-controlled multicenter trial with objective BMD measures; measures PINP (a collagen formation marker) indirectly related to collagen biology.

Study Details

PMID:16449339
Participants:238
Impact:increased at 1 and 3 months; each SD increase in 3-month PINP change associated with +21% QCT spine trabecular BMD
Trust score:4/5

Radiographic subcrestal horizontal bone gain

1 evidences

In 24 patients, rhBMP-2 delivered on an absorbable collagen sponge (ACS) produced greater immediate subcrestal radiographic horizontal bone gain than autogenous graft; clinical gains at 6 months were similar.

Trust comment: Randomized controlled clinical trial with objective radiographic and clinical endpoints but small sample size (proof-of-concept).

Study Details

PMID:23998375
Participants:24
Impact:rhBMP-2/ACS 1.5±0.7 mm vs autograft 0.5±0.9 mm (difference ≈+1.0 mm; p=0.01)
Trust score:4/5

Clinical horizontal bone gain at 6 months

1 evidences

In 24 patients, rhBMP-2 delivered on an absorbable collagen sponge (ACS) produced greater immediate subcrestal radiographic horizontal bone gain than autogenous graft; clinical gains at 6 months were similar.

Trust comment: Randomized controlled clinical trial with objective radiographic and clinical endpoints but small sample size (proof-of-concept).

Study Details

PMID:23998375
Participants:24
Impact:No significant difference: rhBMP-2/ACS 3.2±0.9 mm vs autograft 3.7±1.4 mm (p=0.31)
Trust score:4/5

hs‑CRP (inflammation)

1 evidences

Inflammatory hand OA patients showed biomarker variation; prednisolone did not change most collagen-related biomarkers over 6 weeks.

Trust comment: Post-hoc biomarker analysis of an RCT with moderate sample size; assays well described but limited by short treatment duration and exploratory nature.

Study Details

PMID:35946535
Participants:78
Impact:higher in erosive disease (geometric mean ratio 1.91) and not reduced by prednisolone in serum
Trust score:3/5

Residual graft material (%)

1 evidences

Compared two xenograft ridge-preservation protocols in humans; the protocol using a cross-linked bovine collagen sponge produced more vital bone than the other, while clinical dimensional changes were similar.

Trust comment: Randomized controlled trial with histologic endpoints in 44 patients; moderate sample and clear results support moderate-high trust.

Study Details

PMID:22680300
Participants:44
Impact:-13.44 percentage points (13.44% vs 0%)
Trust score:4/5

buccal plate regeneration

1 evidences

rhBMP-2 on an absorbable collagen sponge regenerated more buccal bone and preserved ridge dimensions better than collagen sponge alone after flapless extraction.

Trust comment: Randomized controlled clinical trial directly comparing collagen sponge alone versus collagen carrier with rhBMP-2; moderate sample size and clear radiographic/clinical endpoints.

Study Details

PMID:23826643
Participants:39
Impact:4.75 mm (rhBMP-2/ACS) vs 1.85 mm (collagen sponge) at 5 months
Trust score:4/5

clinical ridge width at 5 months

1 evidences

rhBMP-2 on an absorbable collagen sponge regenerated more buccal bone and preserved ridge dimensions better than collagen sponge alone after flapless extraction.

Trust comment: Randomized controlled clinical trial directly comparing collagen sponge alone versus collagen carrier with rhBMP-2; moderate sample size and clear radiographic/clinical endpoints.

Study Details

PMID:23826643
Participants:39
Impact:6.00 mm (rhBMP-2/ACS) vs 4.62 mm (collagen sponge)
Trust score:4/5

remaining buccal dehiscence (clinical)

1 evidences

rhBMP-2 on an absorbable collagen sponge regenerated more buccal bone and preserved ridge dimensions better than collagen sponge alone after flapless extraction.

Trust comment: Randomized controlled clinical trial directly comparing collagen sponge alone versus collagen carrier with rhBMP-2; moderate sample size and clear radiographic/clinical endpoints.

Study Details

PMID:23826643
Participants:39
Impact:6.81 mm (rhBMP-2/ACS) vs 10.00 mm (collagen sponge) at 5 months
Trust score:4/5

implant failure rate

2 evidences

Immediate implants with or without anorganic bovine bone + resorbable collagen barrier were compared over 3 years; no difference in implant failures but graft+collagen group showed greater marginal bone loss and worse esthetic/patient satisfaction.

Trust comment: Multicenter randomized controlled trial with 3‑year follow‑up and objective measures, but moderate sample size and mixed implant counts.

Study Details

PMID:30260821
Participants:102
Impact:1 implant failed in each group (no difference)
Trust score:4/5

Randomized multicenter trial comparing immediate post-extractive implants vs delayed implants (delayed group received socket preservation with bovine bone and a resorbable collagen barrier); aesthetics similar, more complications with immediate implants.

Trust comment: Multicenter randomized trial with blinded assessors and 1-year follow-up; collagen membrane was used in the delayed (socket preservation) arm but not isolated as a single factor.

Study Details

PMID:26669545
Participants:106
Impact:Immediate 6% vs Delayed 0%
Trust score:4/5

objective response rate (ORR)

1 evidences

Measured circulating collagen neo-peptides in patients with metastatic pancreatic cancer and found that a high C3M/PRO-C3 ratio predicted better response (PFS, OS, ORR) to pegvorhyaluronidase alfa plus chemotherapy.

Trust comment: Randomized phase‑2 clinical trial with blinded biomarker assays and a validation cohort, but exploratory retrospective biomarker analysis and moderate sample size.

Study Details

PMID:33478521
Participants:189
Impact:+27 percentage points (55% vs 28%) in C3M/PRO-C3 high (Stage 1, median cut-off)
Trust score:4/5

serum ICTP (type I collagen degradation)

1 evidences

Combination DMARD therapy suppressed a serum marker of type I collagen degradation (ICTP) early and was linked to less radiographic joint damage over 2 years.

Trust comment: Randomized study (n=182) with clinically relevant biomarker and radiographic endpoints; assesses collagen degradation rather than collagen supplementation.

Study Details

PMID:18415764
Participants:182
Impact:Decreased from baseline to 1 year (significant)
Trust score:4/5

ICTP at 6 months (COMBI vs SINGLE)

1 evidences

Combination DMARD therapy suppressed a serum marker of type I collagen degradation (ICTP) early and was linked to less radiographic joint damage over 2 years.

Trust comment: Randomized study (n=182) with clinically relevant biomarker and radiographic endpoints; assesses collagen degradation rather than collagen supplementation.

Study Details

PMID:18415764
Participants:182
Impact:Lower in COMBI (p=0.008); lower ICTP associated with less radiographic progression
Trust score:4/5

interleukin-6 (IL-6)

1 evidences

Randomized comparison of femoral closure devices including AngioSeal (anchor + collagen sponge) showed no device-related differences in systemic inflammatory markers; IL-6 rose at 6 hours in all groups.

Trust comment: Randomized study with biomarker endpoints and adequate reporting showing no device-specific systemic inflammatory effect.

Study Details

PMID:18398639
Participants:77
Impact:increased at 6 h postprocedure in all groups (p<0.01) with no between-group difference
Trust score:4/5

skin roughness

1 evidences

Topical product containing collagen tripeptide improved objective skin barrier measures and reduced symptoms of sensitive atopic skin versus placebo over 4 weeks.

Trust comment: Randomized double-blind placebo-controlled human trial but small (n=40) and short duration (4 weeks), so moderate confidence.

Study Details

PMID:19496838
Participants:40
Impact:decreased (P<0.02)
Trust score:3/5

pain during squats

1 evidences

Randomized double-blind placebo-controlled trial: 5 g/day specific collagen peptides for 12 weeks reduced activity-related knee pain versus placebo in physically active young adults.

Trust comment: Well-powered randomized double-blind placebo-controlled trial with pre-registered design and per-protocol and intention-to-treat analyses, but results apply to a specific collagen peptide formulation.

Study Details

PMID:33562729
Participants:180
Impact:improved within groups but between-group differences not statistically significant
Trust score:4/5

resting pain

1 evidences

Randomized double-blind placebo-controlled trial: 5 g/day specific collagen peptides for 12 weeks reduced activity-related knee pain versus placebo in physically active young adults.

Trust comment: Well-powered randomized double-blind placebo-controlled trial with pre-registered design and per-protocol and intention-to-treat analyses, but results apply to a specific collagen peptide formulation.

Study Details

PMID:33562729
Participants:180
Impact:improved within groups but no significant between-group difference (low baseline prevalence)
Trust score:4/5

complete joint fusion at 24 weeks

1 evidences

rhPDGF-BB combined with a β-TCP–collagen matrix (osteoconductive, calcium phosphate–based) produced higher fusion rates, faster time to fusion, and higher clinical success versus autograft in ankle/hindfoot fusions.

Trust comment: Level I randomized trial using a collagen-containing matrix with strong clinical endpoints; high-quality design though historical control data were also included.

Study Details

PMID:25848134
Participants:75
Impact:84% vs 65% (+19 percentage points)
Trust score:4/5

time to fusion

1 evidences

rhPDGF-BB combined with a β-TCP–collagen matrix (osteoconductive, calcium phosphate–based) produced higher fusion rates, faster time to fusion, and higher clinical success versus autograft in ankle/hindfoot fusions.

Trust comment: Level I randomized trial using a collagen-containing matrix with strong clinical endpoints; high-quality design though historical control data were also included.

Study Details

PMID:25848134
Participants:75
Impact:14.3 weeks vs 19.7 weeks (−5.4 weeks)
Trust score:4/5

clinical success at 52 weeks

1 evidences

rhPDGF-BB combined with a β-TCP–collagen matrix (osteoconductive, calcium phosphate–based) produced higher fusion rates, faster time to fusion, and higher clinical success versus autograft in ankle/hindfoot fusions.

Trust comment: Level I randomized trial using a collagen-containing matrix with strong clinical endpoints; high-quality design though historical control data were also included.

Study Details

PMID:25848134
Participants:75
Impact:91% vs 78% (+13 percentage points)
Trust score:4/5

serum C-telopeptide of type I collagen (CTX)

1 evidences

Ibandronate and alendronate both increased BMD over 1 year; all women also received daily calcium and vitamin D 200 IU.

Trust comment: Multicenter randomized positive-control trial with 158 randomized (151 completed) and objective BMD/biomarker endpoints; good internal validity.

Study Details

PMID:19855926
Participants:151
Impact:decrease (significant by 1 month, maintained through 12 months)
Trust score:4/5

MMP-9 level

1 evidences

In 96 uncontrolled hypertensive patients, antihypertensive treatment reduced MMP-9 and increased TIMP-1, indicating altered collagen/ECM turnover after therapy.

Trust comment: Well-defined substudy of a large cardiovascular trial with before/after measurements in 96 patients, but biomarker-only outcomes limit clinical endpoints.

Study Details

PMID:15363817
Participants:96
Impact:decreased after treatment (statistically significant, P=0.035)
Trust score:4/5

TIMP-1 level

1 evidences

In 96 uncontrolled hypertensive patients, antihypertensive treatment reduced MMP-9 and increased TIMP-1, indicating altered collagen/ECM turnover after therapy.

Trust comment: Well-defined substudy of a large cardiovascular trial with before/after measurements in 96 patients, but biomarker-only outcomes limit clinical endpoints.

Study Details

PMID:15363817
Participants:96
Impact:increased after treatment (statistically significant, P=0.005)
Trust score:4/5

CTX (collagen type 1 C-telopeptide)

1 evidences

In 78 overweight schizophrenia patients with prediabetes, 16 weeks of liraglutide did not change bone turnover markers (CTX, P1NP) versus placebo.

Trust comment: Randomized placebo-controlled trial with clearly reported biomarker outcomes and sample size, though moderate duration (16 weeks) limits long-term inference.

Study Details

PMID:33373806
Participants:78
Impact:no significant change vs placebo after 16 weeks
Trust score:4/5

P1NP (procollagen type 1 N-terminal propeptide)

2 evidences

In 78 overweight schizophrenia patients with prediabetes, 16 weeks of liraglutide did not change bone turnover markers (CTX, P1NP) versus placebo.

Trust comment: Randomized placebo-controlled trial with clearly reported biomarker outcomes and sample size, though moderate duration (16 weeks) limits long-term inference.

Study Details

PMID:33373806
Participants:78
Impact:no significant change vs placebo after 16 weeks
Trust score:4/5

12-week randomized dietary supplement trial in adults with abdominal obesity; whey protein increased urinary calcium but did not change bone turnover markers or BMD.

Trust comment: Randomized controlled intervention with objective biochemical measures and reasonable sample size, but post-hoc analysis and limited duration.

Study Details

PMID:35422766
Participants:64
Impact:no significant change after 12 weeks
Trust score:4/5

PINP, tALP, bALP, ICTP

1 evidences

In 77 men with bone-metastatic prostate cancer on zoledronic acid, most bone turnover markers fell after treatment; several markers were higher in patients with progressive bone disease.

Trust comment: Prospective serial biomarker study with defined clinical endpoints and reasonable sample size, but observational comparisons within treated patients limit causal claims.

Study Details

PMID:17321667
Participants:77
Impact:levels were higher in patients with metastatic bone progression vs those without at multiple timepoints
Trust score:4/5

Procollagen type III N-terminal peptide (PIIINP)

1 evidences

In 31 stable chronic heart failure patients, spironolactone reduced a circulating procollagen III peptide and improved heart rate variability and early-morning heart rate.

Trust comment: Randomized double-blind design but small sample size and some analyses on subsets (HRV n=24) reduce robustness.

Study Details

PMID:9302344
Participants:31
Impact:decreased with spironolactone treatment
Trust score:3/5

Heart rate variability (time-domain parameters)

1 evidences

In 31 stable chronic heart failure patients, spironolactone reduced a circulating procollagen III peptide and improved heart rate variability and early-morning heart rate.

Trust comment: Randomized double-blind design but small sample size and some analyses on subsets (HRV n=24) reduce robustness.

Study Details

PMID:9302344
Participants:31
Impact:improved (increased) in treated patients (n=24 for HRV analysis)
Trust score:3/5

Morning heart rate (dawn rise)

1 evidences

In 31 stable chronic heart failure patients, spironolactone reduced a circulating procollagen III peptide and improved heart rate variability and early-morning heart rate.

Trust comment: Randomized double-blind design but small sample size and some analyses on subsets (HRV n=24) reduce robustness.

Study Details

PMID:9302344
Participants:31
Impact:reduced with spironolactone (prolonged RR interval between 06:00–09:00)
Trust score:3/5

C1M (MMP-degraded type I collagen)

1 evidences

In 585 RA patients, serum C1M (MMP-degraded type I collagen) correlated with disease activity and predicted radiographic progression; tocilizumab dose-dependently reduced C1M (rapid ~49% drop at 2 weeks with sustained lowering at higher dose).

Trust comment: Large randomized controlled trial biomarker substudy with robust serial measurements, strong statistical analysis and clinically relevant radiographic endpoints.

Study Details

PMID:23945134
Participants:585
Impact:baseline C1M predicted radiographic progression (OR JSN 3.15, mTSS 2.94); TCZ reduced C1M ~49% at Week 2 with sustained lower levels at 8 mg/kg
Trust score:5/5

Radiographic progression (JSN, mTSS)

1 evidences

In 585 RA patients, serum C1M (MMP-degraded type I collagen) correlated with disease activity and predicted radiographic progression; tocilizumab dose-dependently reduced C1M (rapid ~49% drop at 2 weeks with sustained lowering at higher dose).

Trust comment: Large randomized controlled trial biomarker substudy with robust serial measurements, strong statistical analysis and clinically relevant radiographic endpoints.

Study Details

PMID:23945134
Participants:585
Impact:higher baseline C1M associated with greater progression at 24 and 52 weeks (significant correlations and increased odds ratios)
Trust score:5/5

serum bone-specific alkaline phosphatase (BAP)

2 evidences

Multicenter randomized trial of once-weekly alendronate in postmenopausal Chinese women; not designed to test Vitamin D effects.

Trust comment: Large randomized double-blind placebo-controlled multicenter trial (n=560) with objective BMD and bone turnover endpoints; high reliability.

Study Details

PMID:19343272
Participants:560
Impact:decrease (significant at 12 months)
Trust score:4/5

Randomized substudy comparing tamoxifen, exemestane, and anastrozole over 2 years; tamoxifen was associated with lower bone turnover markers (NTX and BAP) versus the two aromatase inhibitors, with BMD trends favoring tamoxifen though not always significant.

Trust comment: Randomized substudy with objective bone markers but limited sample size reduces precision for BMD comparisons.

Study Details

PMID:21430407
Participants:68
Impact:significantly lower in tamoxifen vs exemestane/anastrozole at 1 and 2 years (p<0.05)
Trust score:3/5

PRO-C2 (type II collagen formation marker)

1 evidences

Lower baseline PRO-C2 (a marker of type II collagen formation) identifies patients with faster radiographic knee OA progression and higher odds of progression.

Trust comment: Post-hoc analysis of two human OA cohorts with well-described methods and moderate sample size; exploratory biomarker work limits causal claims.

Study Details

PMID:33687578
Participants:253
Impact:Very low baseline associated with greater 2‑yr JSN: Q1 vs Q4 mean +0.65 mm JSN; OR progression 3.4× (p=0.0087).
Trust score:4/5

Medial joint space narrowing (radiographic progression)

1 evidences

Lower baseline PRO-C2 (a marker of type II collagen formation) identifies patients with faster radiographic knee OA progression and higher odds of progression.

Trust comment: Post-hoc analysis of two human OA cohorts with well-described methods and moderate sample size; exploratory biomarker work limits causal claims.

Study Details

PMID:33687578
Participants:253
Impact:Low PRO-C2 groups had increased 2‑yr JSN (NYU mean diff +0.52 mm, p=0.0078; SMC placebo mean diff +0.24 mm, p=0.078).
Trust score:4/5

Response to salmon calcitonin (sCT)

1 evidences

Lower baseline PRO-C2 (a marker of type II collagen formation) identifies patients with faster radiographic knee OA progression and higher odds of progression.

Trust comment: Post-hoc analysis of two human OA cohorts with well-described methods and moderate sample size; exploratory biomarker work limits causal claims.

Study Details

PMID:33687578
Participants:253
Impact:In low PRO-C2 subgroup fewer non-responders with sCT vs placebo (29% vs 55%, Chi² p=0.011); sCT increased PRO-C2 ≈+20% (placebo ≈+15%, NS).
Trust score:4/5

Baseline NTX (N‑telopeptide of type I collagen)

1 evidences

High levels of a collagen breakdown marker (NTX) predicted worse bone outcomes and death; zoledronic acid reduced mortality risk in patients with high NTX.

Trust comment: Retrospective analysis of randomized trial data with moderate sample size; associations and subgroup effects reported but causality limited by post-hoc nature.

Study Details

PMID:18317064
Participants:382
Impact:High vs normal NTX associated with ≈>2× increased risk of bone lesion progression and death in placebo group (p≈0.039 and p=0.001).
Trust score:3/5

Zoledronic acid effect in high‑NTX patients

1 evidences

High levels of a collagen breakdown marker (NTX) predicted worse bone outcomes and death; zoledronic acid reduced mortality risk in patients with high NTX.

Trust comment: Retrospective analysis of randomized trial data with moderate sample size; associations and subgroup effects reported but causality limited by post-hoc nature.

Study Details

PMID:18317064
Participants:382
Impact:Among high baseline NTX patients, ZOL reduced relative risk of death by 35% vs placebo (p=0.024).
Trust score:3/5

Serum PICP (type I collagen C‑terminal propeptide, bone formation)

1 evidences

A daily combined massage and physical activity protocol increased a serum bone formation marker but did not reduce markers of bone resorption in preterm infants.

Trust comment: Small double‑blind randomized trial in preterm infants; randomized design strengthens inference but limited by small N.

Study Details

PMID:15071483
Participants:30
Impact:Intervention group increased from 62.5 to 73.8 (units) over hospitalization; regression coef +18.8 (±4.6), p=0.0001.
Trust score:3/5

Urinary Pyd (pyridinoline, bone resorption)

1 evidences

A daily combined massage and physical activity protocol increased a serum bone formation marker but did not reduce markers of bone resorption in preterm infants.

Trust comment: Small double‑blind randomized trial in preterm infants; randomized design strengthens inference but limited by small N.

Study Details

PMID:15071483
Participants:30
Impact:Pyd increased over time in both groups with no significant difference between groups (no effect of intervention, p≈0.96).
Trust score:3/5

Radiographic bone erosion progression

1 evidences

Tocilizumab monotherapy reduced 1‑year radiographic erosion and joint‑space narrowing most markedly in patients classified as high‑risk by collagen and other biomarkers.

Trust comment: Prospective randomized controlled trial subanalysis with blinded radiographic scoring; good design though subgroup analyses reduce power.

Study Details

PMID:20574648
Participants:302
Impact:Tocilizumab reduced 1‑yr change in erosion scores in high‑risk groups (high uCTX‑II or uPYD/DPD, low BMI) vs conventional DMARDs (statistically significant).
Trust score:4/5

Joint space narrowing (JSN) progression

1 evidences

Tocilizumab monotherapy reduced 1‑year radiographic erosion and joint‑space narrowing most markedly in patients classified as high‑risk by collagen and other biomarkers.

Trust comment: Prospective randomized controlled trial subanalysis with blinded radiographic scoring; good design though subgroup analyses reduce power.

Study Details

PMID:20574648
Participants:302
Impact:Tocilizumab reduced 1‑yr JSN progression in high‑risk subgroups (high JSN or low BMI) compared with DMARDs (significant in several high‑risk strata).
Trust score:4/5

Collagen type I C‑telopeptide (CTX, bone resorption)

1 evidences

In Mexican postmenopausal women with osteoporosis, bazedoxifene markedly reduced bone turnover markers including a collagen resorption marker versus placebo at 12 months.

Trust comment: Subgroup analysis of a large randomized trial but small Mexican subgroup reduces power and precision; biochemical endpoints robust though.

Study Details

PMID:27116464
Participants:76
Impact:At 12 months C‑telopeptide percent change −45.7% (BZA) vs −29.4% (placebo); difference reported significant (P<0.001).
Trust score:3/5

Elevated bone turnover markers (incl. C‑terminal collagen propeptide)

1 evidences

High serum bone turnover markers (including collagen‑related markers) predicted much worse survival in CRPC with bone metastases; a small high‑marker subgroup derived survival benefit from atrasentan.

Trust comment: Prospective biomarker analysis nested in a large phase III trial with preplanned assays and multivariate adjustment; strong prognostic evidence though predictive subgroup is small.

Study Details

PMID:24565955
Participants:778
Impact:Elevated baseline markers associated with worse survival (upper 25% HR=4.3, p<0.001).
Trust score:4/5

Predictive benefit of atrasentan in highest‑marker subgroup

1 evidences

High serum bone turnover markers (including collagen‑related markers) predicted much worse survival in CRPC with bone metastases; a small high‑marker subgroup derived survival benefit from atrasentan.

Trust comment: Prospective biomarker analysis nested in a large phase III trial with preplanned assays and multivariate adjustment; strong prognostic evidence though predictive subgroup is small.

Study Details

PMID:24565955
Participants:778
Impact:In upper 25% marker subgroup atrasentan vs placebo HR=0.33 for death (median survival 13 vs 5 months); interaction p=0.005.
Trust score:4/5

progression-free survival (PFS)

1 evidences

Measured circulating collagen neo-peptides in patients with metastatic pancreatic cancer and found that a high C3M/PRO-C3 ratio predicted better response (PFS, OS, ORR) to pegvorhyaluronidase alfa plus chemotherapy.

Trust comment: Randomized phase‑2 clinical trial with blinded biomarker assays and a validation cohort, but exploratory retrospective biomarker analysis and moderate sample size.

Study Details

PMID:33478521
Participants:189
Impact:+2.7 months (8.0 vs 5.3 mo) with PAG vs AG in C3M/PRO-C3 high (Stage 1, median cut-off); Stage 2: 8.8 vs 3.4 mo (median cut-off)
Trust score:4/5

overall survival (OS)

1 evidences

Measured circulating collagen neo-peptides in patients with metastatic pancreatic cancer and found that a high C3M/PRO-C3 ratio predicted better response (PFS, OS, ORR) to pegvorhyaluronidase alfa plus chemotherapy.

Trust comment: Randomized phase‑2 clinical trial with blinded biomarker assays and a validation cohort, but exploratory retrospective biomarker analysis and moderate sample size.

Study Details

PMID:33478521
Participants:189
Impact:+5.3 months (13.8 vs 8.5 mo) with PAG vs AG in C3M/PRO-C3 high (Stage 2, median cut-off); up to +8.9 mo using ROC cut-off (17.4 vs 8.5 mo)
Trust score:4/5

WOMAC (OA symptoms)

1 evidences

Four weeks of an oral supplement containing hydrolyzed collagen type II plus HA and CS reduced pain scores and decreased some inflammatory cytokines in synovial fluid of knee OA patients.

Trust comment: Pilot randomized study in 30 patients with short (4-week) duration and small sample size, limiting confidence.

Study Details

PMID:33213125
Participants:30
Impact:improved (p<0.01)
Trust score:3/5

synovial fluid IL-8

1 evidences

Four weeks of an oral supplement containing hydrolyzed collagen type II plus HA and CS reduced pain scores and decreased some inflammatory cytokines in synovial fluid of knee OA patients.

Trust comment: Pilot randomized study in 30 patients with short (4-week) duration and small sample size, limiting confidence.

Study Details

PMID:33213125
Participants:30
Impact:decreased (p=0.015); IL-6 and IL-10 also decreased
Trust score:3/5

Urinary collagen type II fragments

1 evidences

Risedronate plus calcium reduced objective pain measure and was associated with a decrease in urinary type II collagen fragments compared with calcium alone.

Trust comment: Small randomized human trial with objective and subjective pain measures; limited sample size reduces certainty.

Study Details

PMID:18831886
Participants:33
Impact:decrease (associated with pain alleviation)
Trust score:3/5

Pain on exercise (skin impedance/electroalgometry)

1 evidences

Risedronate plus calcium reduced objective pain measure and was associated with a decrease in urinary type II collagen fragments compared with calcium alone.

Trust comment: Small randomized human trial with objective and subjective pain measures; limited sample size reduces certainty.

Study Details

PMID:18831886
Participants:33
Impact:reduced (improved) — objective measure; VRS not changed
Trust score:3/5

Type IV collagen (sputum)

1 evidences

Six months of low-dose roxithromycin reduced airway inflammation, sputum type IV collagen, airway wall thickness, and exacerbations versus control.

Trust comment: Randomized open-label single-center trial with moderate sample and multiple objective measures but limited blinding and size.

Study Details

PMID:25580060
Participants:43
Impact:significant decrease from baseline to 6 months (P<0.001)
Trust score:3/5

Airway wall thickness (WT% and WA%)

1 evidences

Six months of low-dose roxithromycin reduced airway inflammation, sputum type IV collagen, airway wall thickness, and exacerbations versus control.

Trust comment: Randomized open-label single-center trial with moderate sample and multiple objective measures but limited blinding and size.

Study Details

PMID:25580060
Participants:43
Impact:WT% and WA% decreased from baseline to 6 months; significantly lower vs control (P≤0.018/0.001)
Trust score:3/5

Exacerbation rate / time to first exacerbation

1 evidences

Six months of low-dose roxithromycin reduced airway inflammation, sputum type IV collagen, airway wall thickness, and exacerbations versus control.

Trust comment: Randomized open-label single-center trial with moderate sample and multiple objective measures but limited blinding and size.

Study Details

PMID:25580060
Participants:43
Impact:proportion with ≥1 exacerbation: 76.2% → 50.0% (−26.2 percentage points); median time to first exacerbation prolonged (113 → 264 days)
Trust score:3/5

Urinary NTX (cross-linked N-terminal telopeptide of type I collagen)

1 evidences

Alendronate suppressed bone turnover (NTX, ALP) more than elcatonin and produced greater reductions in back pain and improved quality of life over 6 months.

Trust comment: Large randomized controlled trial with high completion and clinically relevant outcomes.

Study Details

PMID:21104227
Participants:193
Impact:significant decrease at 3 months in alendronate group (no change in elcatonin)
Trust score:4/5

Serum alkaline phosphatase (ALP)

1 evidences

Alendronate suppressed bone turnover (NTX, ALP) more than elcatonin and produced greater reductions in back pain and improved quality of life over 6 months.

Trust comment: Large randomized controlled trial with high completion and clinically relevant outcomes.

Study Details

PMID:21104227
Participants:193
Impact:decrease at 6 months in both groups, greater reduction with alendronate
Trust score:4/5

Back pain / QOL

1 evidences

Alendronate suppressed bone turnover (NTX, ALP) more than elcatonin and produced greater reductions in back pain and improved quality of life over 6 months.

Trust comment: Large randomized controlled trial with high completion and clinically relevant outcomes.

Study Details

PMID:21104227
Participants:193
Impact:improved in both groups at 1, 3, 6 months; greater improvement with alendronate
Trust score:4/5

Aminoterminal propeptide of type I procollagen (serum)

1 evidences

Two years of transdermal DHT did not affect prostate growth but increased the aminoterminal propeptide of type I procollagen and altered body composition and blood parameters.

Trust comment: Well-conducted 2-year randomized placebo-controlled trial with objective imaging and biochemical outcomes.

Study Details

PMID:21079217
Participants:114
Impact:increased in the second year vs placebo
Trust score:4/5

Spinal bone mineral density (BMD)

1 evidences

Two years of transdermal DHT did not affect prostate growth but increased the aminoterminal propeptide of type I procollagen and altered body composition and blood parameters.

Trust comment: Well-conducted 2-year randomized placebo-controlled trial with objective imaging and biochemical outcomes.

Study Details

PMID:21079217
Participants:114
Impact:decrease −1.4% over 24 months
Trust score:4/5

Lean and fat mass

1 evidences

Two years of transdermal DHT did not affect prostate growth but increased the aminoterminal propeptide of type I procollagen and altered body composition and blood parameters.

Trust comment: Well-conducted 2-year randomized placebo-controlled trial with objective imaging and biochemical outcomes.

Study Details

PMID:21079217
Participants:114
Impact:lean mass +2.4%; fat mass −5.2% (both significant)
Trust score:4/5

Serum C-telopeptide (S-CTX)

1 evidences

Drinking bicarbonate-rich (alkaline) mineral water for 2–4 weeks reduced serum CTX and PTH compared with an acidic calcium-rich water in young women.

Trust comment: Small randomized dietary intervention with short duration and biochemical endpoints; informative but limited generalizability.

Study Details

PMID:18926940
Participants:30
Impact:decrease with alkaline water (significant vs control, p=0.023)
Trust score:3/5

Procollagen III N-terminal peptide (PIIINP)

1 evidences

Spironolactone reduced ventricular extrasystoles, shortened QT interval, and lowered a collagen synthesis marker (PIIINP) in ischemic heart disease patients without heart failure.

Trust comment: Randomized, double-blind, placebo-controlled crossover study with robust electrophysiologic and biochemical endpoints.

Study Details

PMID:17921831
Participants:98
Impact:mean decrease from 3.6 to 3.0 (P<0.001)
Trust score:4/5

Ventricular extrasystoles

1 evidences

Spironolactone reduced ventricular extrasystoles, shortened QT interval, and lowered a collagen synthesis marker (PIIINP) in ischemic heart disease patients without heart failure.

Trust comment: Randomized, double-blind, placebo-controlled crossover study with robust electrophysiologic and biochemical endpoints.

Study Details

PMID:17921831
Participants:98
Impact:~75% median reduction vs placebo (median 192 → 48)
Trust score:4/5

QT interval

1 evidences

Spironolactone reduced ventricular extrasystoles, shortened QT interval, and lowered a collagen synthesis marker (PIIINP) in ischemic heart disease patients without heart failure.

Trust comment: Randomized, double-blind, placebo-controlled crossover study with robust electrophysiologic and biochemical endpoints.

Study Details

PMID:17921831
Participants:98
Impact:decrease from mean 440 ms to 425 ms (P<0.001)
Trust score:4/5

WOMAC score (OA severity)

1 evidences

A 6-month randomized trial found the product containing undenatured type II collagen (Artneo) improved pain, stiffness, and some MRI signs of synovitis and was not inferior to glucosamine+chondroitin.

Trust comment: Randomized clinical trial directly testing an undenatured type II collagen-containing product but small sample (n=70) and limited power; moderate confidence.

Study Details

PMID:38785054
Participants:70
Impact:improved in both groups; Artneo non-inferior to glucosamine+chondroitin
Trust score:3/5

morning stiffness and synovitis area (MRI)

1 evidences

A 6-month randomized trial found the product containing undenatured type II collagen (Artneo) improved pain, stiffness, and some MRI signs of synovitis and was not inferior to glucosamine+chondroitin.

Trust comment: Randomized clinical trial directly testing an undenatured type II collagen-containing product but small sample (n=70) and limited power; moderate confidence.

Study Details

PMID:38785054
Participants:70
Impact:greater decrease in stiffness with Artneo; synovitis area reduced 2.95x (Artneo) vs 1.37x (GC)
Trust score:3/5

Total WOMAC score (symptoms)

1 evidences

A multicenter randomized double-blind trial of undenatured type II collagen (UC-II) in knee OA (mITT n=186) showed significant reductions in total WOMAC and subscale scores, less rescue medication use, and was well tolerated.

Trust comment: Large multicenter randomized double-blind placebo-controlled trial with robust clinical endpoints showing consistent symptomatic benefit for undenatured type II collagen (UC-II).

Study Details

PMID:26822714
Participants:186
Impact:Change at day 180: −551 (UC-II) vs −414 (placebo); p=0.002
Trust score:4/5

Mean VAS (pain)

1 evidences

A multicenter randomized double-blind trial of undenatured type II collagen (UC-II) in knee OA (mITT n=186) showed significant reductions in total WOMAC and subscale scores, less rescue medication use, and was well tolerated.

Trust comment: Large multicenter randomized double-blind placebo-controlled trial with robust clinical endpoints showing consistent symptomatic benefit for undenatured type II collagen (UC-II).

Study Details

PMID:26822714
Participants:186
Impact:Greater decrease at day 180: 22.6 vs 17.0 (UC-II vs placebo); p=0.002
Trust score:4/5

Rescue medication use

1 evidences

A multicenter randomized double-blind trial of undenatured type II collagen (UC-II) in knee OA (mITT n=186) showed significant reductions in total WOMAC and subscale scores, less rescue medication use, and was well tolerated.

Trust comment: Large multicenter randomized double-blind placebo-controlled trial with robust clinical endpoints showing consistent symptomatic benefit for undenatured type II collagen (UC-II).

Study Details

PMID:26822714
Participants:186
Impact:Fewer users in UC-II group (11/63) vs placebo (28/58); p=0.001
Trust score:4/5

HbA1c

1 evidences

Pyridoxamine tended to raise a bone formation marker, increased femoral neck BMD, and slightly lowered HbA1c in older women with T2D.

Trust comment: Double-blind RCT with modest sample size showing significant BMD and HbA1c changes, though some outcomes are borderline.

Study Details

PMID:39376018
Participants:55
Impact:PM -0.38% vs placebo +0.05% (between-groups P=0.04)
Trust score:4/5

WOMAC total score

1 evidences

Randomized double-blind 30-day trial (67 completers) found Aflapin reduced knee pain and improved function; collagen type II cleavage biomarker (C2C) and inflammatory biomarkers decreased.

Trust comment: Randomized, double-blind, placebo-controlled trial with objective biomarker and clinical endpoints but small, short-duration study.

Study Details

PMID:35512759
Participants:67
Impact:−48% in Aflapin group (significant vs placebo)
Trust score:4/5

histological activity index (HAI)

1 evidences

IFN-beta-1a therapy reduced liver inflammation, fibrosis, and collagen III levels in patients with chronic hepatitis C.

Trust comment: Small randomized human study with biopsy-based endpoints and significant within-subject changes but limited sample size (n=21).

Study Details

PMID:18353212
Participants:21
Impact:-2.3 points (6.6 → 4.3)
Trust score:3/5

fibrosis score

1 evidences

IFN-beta-1a therapy reduced liver inflammation, fibrosis, and collagen III levels in patients with chronic hepatitis C.

Trust comment: Small randomized human study with biopsy-based endpoints and significant within-subject changes but limited sample size (n=21).

Study Details

PMID:18353212
Participants:21
Impact:-0.6 points (1.7 → 1.1)
Trust score:3/5

collagen type III level (integrated light density)

1 evidences

IFN-beta-1a therapy reduced liver inflammation, fibrosis, and collagen III levels in patients with chronic hepatitis C.

Trust comment: Small randomized human study with biopsy-based endpoints and significant within-subject changes but limited sample size (n=21).

Study Details

PMID:18353212
Participants:21
Impact:-6 units (16 → 10)
Trust score:3/5

type-I collagen β C-telopeptide (bone resorption marker)

1 evidences

In AGHD patients receiving GH replacement, adding oral phosphate or alendronate increased markers of bone activity and produced greater BMD increases compared with GH alone; vitamin D was not studied.

Trust comment: Randomized clinical study with objective BMD and biochemical endpoints but moderate sample size and complex group structure.

Study Details

PMID:21252245
Participants:44
Impact:decreased with GHR + alendronate (P < 0.001 vs GHR alone)
Trust score:3/5

nephrogenous cAMP / bone formation markers

1 evidences

In AGHD patients receiving GH replacement, adding oral phosphate or alendronate increased markers of bone activity and produced greater BMD increases compared with GH alone; vitamin D was not studied.

Trust comment: Randomized clinical study with objective BMD and biochemical endpoints but moderate sample size and complex group structure.

Study Details

PMID:21252245
Participants:44
Impact:increased with GHR + phosphate (P < 0.01 vs GHR)
Trust score:3/5

endostatin (EST) level

1 evidences

Combination lisinopril+verapamil reduced angiogenic markers and albuminuria in hypertensive T2DM patients with microalbuminuria.

Trust comment: Randomized trial with clear biochemical endpoints but modest sample size and short follow-up (3 months).

Study Details

PMID:34282598
Participants:40
Impact:significantly decreased with lisinopril + verapamil vs baseline and vs lisinopril alone (P < 0.001)
Trust score:3/5

angiopoietin-2 (Ang-2) level

1 evidences

Combination lisinopril+verapamil reduced angiogenic markers and albuminuria in hypertensive T2DM patients with microalbuminuria.

Trust comment: Randomized trial with clear biochemical endpoints but modest sample size and short follow-up (3 months).

Study Details

PMID:34282598
Participants:40
Impact:significantly decreased with lisinopril + verapamil vs baseline and vs lisinopril alone (P < 0.001)
Trust score:3/5

urinary albumin-creatinine ratio (UACR)

1 evidences

Combination lisinopril+verapamil reduced angiogenic markers and albuminuria in hypertensive T2DM patients with microalbuminuria.

Trust comment: Randomized trial with clear biochemical endpoints but modest sample size and short follow-up (3 months).

Study Details

PMID:34282598
Participants:40
Impact:decreased with lisinopril + verapamil vs baseline and vs lisinopril alone (P < 0.001)
Trust score:3/5

urine N-telopeptide of type I collagen (resorption marker)

1 evidences

Zoledronic acid produced larger reductions in type I collagen resorption marker and bone formation marker than raloxifene in postmenopausal women with low bone density.

Trust comment: Multicenter, randomized, double-blind trial with a reasonable sample size (n=110) and consistent biochemical endpoints.

Study Details

PMID:21796066
Participants:110
Impact:significantly greater reduction with zoledronic acid vs raloxifene at 6 months (P < 0.001)
Trust score:4/5

serum bone-specific alkaline phosphatase (formation marker)

1 evidences

Zoledronic acid produced larger reductions in type I collagen resorption marker and bone formation marker than raloxifene in postmenopausal women with low bone density.

Trust comment: Multicenter, randomized, double-blind trial with a reasonable sample size (n=110) and consistent biochemical endpoints.

Study Details

PMID:21796066
Participants:110
Impact:greater decreases with zoledronic acid vs raloxifene at 2, 4, and 6 months (P < 0.001)
Trust score:4/5

knee muscle strength

1 evidences

In athletes with early knee arthritis, 12 weeks of collagen supplementation reduced pain from baseline but was not superior to exercise; combined collagen+exercise improved several functional outcomes.

Trust comment: Quasi‑randomized, blinded trial with modest sample size and short (12‑week) collagen exposure limiting long‑term conclusions.

Study Details

PMID:38063519
Participants:48
Impact:flexor and extensor strength improved in all groups (p<0.001)
Trust score:3/5

Proportion reporting joint pain

1 evidences

Placebo-controlled RCT of AR7 (contains sternum collagen type II among other ingredients) for 3 months showed reduced joint pain and improved body pain scores.

Trust comment: Randomized, placebo-controlled and blinded with 89 completers, but short duration (3 months) and multi-ingredient product limits attribution solely to collagen.

Study Details

PMID:18954461
Participants:89
Impact:43.2% (treatment) vs 71.1% (control) after 12 weeks
Trust score:3/5

Proportion reporting joint stiffness

1 evidences

Placebo-controlled RCT of AR7 (contains sternum collagen type II among other ingredients) for 3 months showed reduced joint pain and improved body pain scores.

Trust comment: Randomized, placebo-controlled and blinded with 89 completers, but short duration (3 months) and multi-ingredient product limits attribution solely to collagen.

Study Details

PMID:18954461
Participants:89
Impact:22.7% (treatment) vs 42.2% (control) after 12 weeks
Trust score:3/5

SF-36 body pain score

1 evidences

Placebo-controlled RCT of AR7 (contains sternum collagen type II among other ingredients) for 3 months showed reduced joint pain and improved body pain scores.

Trust comment: Randomized, placebo-controlled and blinded with 89 completers, but short duration (3 months) and multi-ingredient product limits attribution solely to collagen.

Study Details

PMID:18954461
Participants:89
Impact:improved to 64.07 (treatment) vs 55.76 (control) after 12 weeks
Trust score:3/5

Medial perimeniscal synovitis (CE-MRI)

1 evidences

In a cross-sectional analysis of participants from the VIDEO trial (n≈447 with serum data; n=136 with CE‑MRI), site-specific CE‑MRI synovitis (medial perimeniscal, suprapatellar) associated with worse knee pain/function, and certain serum matrix-turnover markers (C3M, CRPM) showed negative associations with pain.

Trust comment: Large secondary cross-sectional analysis of a randomized trial with robust biomarker and MRI measures, but cross-sectional design limits causal inference.

Study Details

PMID:34359996
Participants:447
Impact:+9.83 WOMAC pain points (95% CI 1.33 to 18.32) versus no synovitis
Trust score:3/5

C3M (type III collagen degradation fragment)

1 evidences

In a cross-sectional analysis of participants from the VIDEO trial (n≈447 with serum data; n=136 with CE‑MRI), site-specific CE‑MRI synovitis (medial perimeniscal, suprapatellar) associated with worse knee pain/function, and certain serum matrix-turnover markers (C3M, CRPM) showed negative associations with pain.

Trust comment: Large secondary cross-sectional analysis of a randomized trial with robust biomarker and MRI measures, but cross-sectional design limits causal inference.

Study Details

PMID:34359996
Participants:447
Impact:-6.97 WOMAC pain points (3rd quartile vs lowest, adjusted)
Trust score:3/5

CRPM (CRP neo-epitope)

1 evidences

In a cross-sectional analysis of participants from the VIDEO trial (n≈447 with serum data; n=136 with CE‑MRI), site-specific CE‑MRI synovitis (medial perimeniscal, suprapatellar) associated with worse knee pain/function, and certain serum matrix-turnover markers (C3M, CRPM) showed negative associations with pain.

Trust comment: Large secondary cross-sectional analysis of a randomized trial with robust biomarker and MRI measures, but cross-sectional design limits causal inference.

Study Details

PMID:34359996
Participants:447
Impact:-7.40 WOMAC pain points (3rd quartile vs lowest, adjusted); -5.94 WOMAC function points (3rd vs lowest)
Trust score:3/5

Parathyroid gland volume

1 evidences

In dialysis patients with early secondary hyperparathyroidism, intermittent intravenous calcitriol prevented parathyroid gland enlargement compared with daily oral calcitriol over 12 months.

Trust comment: Randomized controlled trial (72 randomized, 60 completed) with objective imaging and biochemical outcomes; good internal validity though sample modest.

Study Details

PMID:18515308
Participants:60
Impact:DO group increase (max 49 → 101 mm³, P = 0.007); IV group no significant change (96 → 89 mm³)
Trust score:4/5

N-telopeptide cross-linked of type I collagen (NTX)

1 evidences

In dialysis patients with early secondary hyperparathyroidism, intermittent intravenous calcitriol prevented parathyroid gland enlargement compared with daily oral calcitriol over 12 months.

Trust comment: Randomized controlled trial (72 randomized, 60 completed) with objective imaging and biochemical outcomes; good internal validity though sample modest.

Study Details

PMID:18515308
Participants:60
Impact:DO: significant decrease from 3 months (P < 0.01); IV: significant decrease at 12 months (P < 0.05)
Trust score:4/5

PIIINP level

1 evidences

In people with type 2 diabetes, higher circulating PIIINP marks expanded visceral fat and an inflammatory adipose-tissue profile.

Trust comment: Moderate-quality observational study with direct measurements but a modest sample (n=62) and cross-sectional design limits causal inference.

Study Details

PMID:29471595
Participants:62
Impact:positively correlated with BMI and visceral adipose tissue area (higher PIIINP in adipose-expanded individuals)
Trust score:3/5

Adipose-associated inflammation markers (WISP-1, IL-8, adiponectin)

1 evidences

In people with type 2 diabetes, higher circulating PIIINP marks expanded visceral fat and an inflammatory adipose-tissue profile.

Trust comment: Moderate-quality observational study with direct measurements but a modest sample (n=62) and cross-sectional design limits causal inference.

Study Details

PMID:29471595
Participants:62
Impact:WISP-1 and IL-8 increased; adiponectin decreased (associated with higher PIIINP)
Trust score:3/5

Hepatic fat / NAFLD markers

1 evidences

In people with type 2 diabetes, higher circulating PIIINP marks expanded visceral fat and an inflammatory adipose-tissue profile.

Trust comment: Moderate-quality observational study with direct measurements but a modest sample (n=62) and cross-sectional design limits causal inference.

Study Details

PMID:29471595
Participants:62
Impact:no significant association with PIIINP
Trust score:3/5

Urinary N-telopeptide (NTX) normalization

1 evidences

Among breast cancer patients with bone metastases, early normalization of urinary NTX during zoledronic acid therapy was linked to fewer skeletal events and lower mortality.

Trust comment: Post-hoc subset analysis of a randomized trial with a reasonably large subset but retrospective nature reduces certainty.

Study Details

PMID:17914073
Participants:328
Impact:early normalization (by 3 months) associated with significantly lower risk of first SRE, first fracture or surgery to bone, and death versus persistently elevated NTX
Trust score:3/5

Skeletal-related events (SRE) and death

1 evidences

Among breast cancer patients with bone metastases, early normalization of urinary NTX during zoledronic acid therapy was linked to fewer skeletal events and lower mortality.

Trust comment: Post-hoc subset analysis of a randomized trial with a reasonably large subset but retrospective nature reduces certainty.

Study Details

PMID:17914073
Participants:328
Impact:reduced incidence in NTX-normalized group (significantly lower risk compared with persistently elevated NTX)
Trust score:3/5

Bone turnover markers (osteocalcin, N-telopeptide)

1 evidences

Bazedoxifene/conjugated estrogens increased spine and hip bone mineral density and reduced bone turnover markers versus placebo in postmenopausal women at risk for osteoporosis.

Trust comment: Large, randomized, double-blind, phase 3 trial providing high-quality evidence for BMD and marker changes.

Study Details

PMID:19635616
Participants:3397
Impact:significant decreases versus placebo
Trust score:4/5

Urinary procollagen III aminoterminal propeptide (PIIINP)

1 evidences

Shockwave lithotripsy caused prolonged increases in a urinary renal fibrosis marker (PIIINP) for up to ~18 months and modest persistent serum creatinine elevation at 2 years.

Trust comment: Prospective randomized study with clear biomarker follow-up and adequate sample size, though clinical consequences beyond markers were limited.

Study Details

PMID:29205049
Participants:320
Impact:significant increase from 6 weeks to 18 months post-SWL; peak at 1 year; returned toward baseline by 2 years
Trust score:4/5

serum creatinine

2 evidences

Shockwave lithotripsy caused prolonged increases in a urinary renal fibrosis marker (PIIINP) for up to ~18 months and modest persistent serum creatinine elevation at 2 years.

Trust comment: Prospective randomized study with clear biomarker follow-up and adequate sample size, though clinical consequences beyond markers were limited.

Study Details

PMID:29205049
Participants:320
Impact:small but statistically significant elevation persisted at 2 years
Trust score:4/5

In 200 CRF patients randomized to autologous MSCs vs N-acetylcysteine, MSCs produced greater improvements in renal function markers and oxidative stress over 8 weeks.

Trust comment: Randomized study with 200 patients and multiple biochemical endpoints; good sample size though described as a pilot and limited to 8-week follow-up.

Study Details

PMID:34602393
Participants:200
Impact:decreased more with MSCs vs NACys (statistically significant)
Trust score:4/5

Blood pressure control / new hypertension

1 evidences

Shockwave lithotripsy caused prolonged increases in a urinary renal fibrosis marker (PIIINP) for up to ~18 months and modest persistent serum creatinine elevation at 2 years.

Trust comment: Prospective randomized study with clear biomarker follow-up and adequate sample size, though clinical consequences beyond markers were limited.

Study Details

PMID:29205049
Participants:320
Impact:9.95% developed new-onset hypertension; additional patients had worsened BP control (reported 36.4%)
Trust score:4/5

Bone ALP isoforms (B1, B2)

1 evidences

In GH-deficient adults, IGF-I and GH therapy produced distinct changes in bone alkaline phosphatase isoforms and increased several bone turnover markers, indicating stimulation of type I collagen synthesis.

Trust comment: Small interventional cohort with detailed biochemical measures but limited sample size (n=22) restricts generalizability.

Study Details

PMID:9041052
Participants:22
Impact:B1 decreased after short IGF-I/GH exposure then B1 and B2 increased after 3 months of GH therapy
Trust score:3/5

Type I collagen synthesis marker (PICP)

1 evidences

In GH-deficient adults, IGF-I and GH therapy produced distinct changes in bone alkaline phosphatase isoforms and increased several bone turnover markers, indicating stimulation of type I collagen synthesis.

Trust comment: Small interventional cohort with detailed biochemical measures but limited sample size (n=22) restricts generalizability.

Study Details

PMID:9041052
Participants:22
Impact:PICP increased early, preceding increases in bone ALP and osteocalcin
Trust score:3/5

Other bone turnover markers (osteocalcin, ICTP, urinary pyridinoline)

1 evidences

In GH-deficient adults, IGF-I and GH therapy produced distinct changes in bone alkaline phosphatase isoforms and increased several bone turnover markers, indicating stimulation of type I collagen synthesis.

Trust comment: Small interventional cohort with detailed biochemical measures but limited sample size (n=22) restricts generalizability.

Study Details

PMID:9041052
Participants:22
Impact:increased during GH therapy
Trust score:3/5

Urinary N-telopeptide (uNTx) normalization

1 evidences

In patients with elevated urinary N-telopeptide despite IV bisphosphonates, denosumab more frequently normalized uNTx and was associated with fewer on-study SREs than continuing IV bisphosphonates.

Trust comment: Randomized phase II trial with clear biochemical and clinical endpoints but modest sample size (n=111) limits power for some outcomes.

Study Details

PMID:19237632
Participants:111
Impact:uNTx <50 at week 13 achieved in 71% of denosumab arms vs 29% of IV BP arm; maintained at week 25 (64% vs 37%)
Trust score:4/5

Skeletal-related events (SRE) incidence

1 evidences

In patients with elevated urinary N-telopeptide despite IV bisphosphonates, denosumab more frequently normalized uNTx and was associated with fewer on-study SREs than continuing IV bisphosphonates.

Trust comment: Randomized phase II trial with clear biochemical and clinical endpoints but modest sample size (n=111) limits power for some outcomes.

Study Details

PMID:19237632
Participants:111
Impact:lower on-study SREs in denosumab group (8% denosumab vs 17% IV BP)
Trust score:4/5

PIIINP (serum)

1 evidences

Observational cohort (n=142) showing higher baseline serum PIIINP (type III procollagen N-peptide) in patients with AF recurrence and that PIIINP independently predicted recurrence after cardioversion.

Trust comment: Moderate-sized clinical cohort with biomarker measurement and multivariable analysis, but observational design limits causal inference.

Study Details

PMID:22622138
Participants:142
Impact:higher in AF recurrence group (0.664 vs 0.581 U/mL); independent predictor (OR 2.61, P=0.008)
Trust score:3/5

BNP (serum)

1 evidences

Randomized study in 93 AMI patients undergoing PCI reporting that Shenfu injection (plus PCI) reduced post-AMI rise in BNP versus PCI alone and was interpreted as ameliorating myocardial injury and preventing fibrosis.

Trust comment: Randomized clinical intervention with relevant biomarkers, but limited detail and reporting in the available abstract/text reduces confidence in effect-size estimates.

Study Details

PMID:15957835
Participants:93
Impact:BNP at 24h and day 7 was lower in treatment group vs control (control showed larger increases; difference at T3 P<0.05)
Trust score:3/5

lumbar spine bone mineral density (L2-L4)

1 evidences

In osteopenic postmenopausal women receiving calcium/magnesium/calcitriol, red clover extract plus probiotics reduced lumbar spine BMD loss and improved bone turnover and estrogen metabolite profile versus placebo.

Trust comment: 12-month double-blind RCT with 78 participants — well-designed but moderate sample size.

Study Details

PMID:28768651
Participants:78
Impact:attenuated BMD loss (statistically significant)
Trust score:4/5

estrogen metabolite profile (2-OH:16α-OH)

1 evidences

In osteopenic postmenopausal women receiving calcium/magnesium/calcitriol, red clover extract plus probiotics reduced lumbar spine BMD loss and improved bone turnover and estrogen metabolite profile versus placebo.

Trust comment: 12-month double-blind RCT with 78 participants — well-designed but moderate sample size.

Study Details

PMID:28768651
Participants:78
Impact:shifted to a more favorable profile (statistically significant)
Trust score:4/5

serum C-terminal propeptide of procollagen type I (PIP)

1 evidences

In 35 HFpEF patients with diabetes, 9 months of torasemide did not change serum PIP compared with furosemide — no effect on collagen synthesis marker or clinical measures.

Trust comment: Randomized, double-blind trial directly measuring collagen-synthesis biomarker but small single-center sample limits confidence.

Study Details

PMID:28891228
Participants:35
Impact:mean % change: torasemide +2.63% ±5.68 vs furosemide +2.74% ±6.49 (P=0.9898; no difference)
Trust score:3/5

functional capacity / diastolic function / QoL

1 evidences

In 35 HFpEF patients with diabetes, 9 months of torasemide did not change serum PIP compared with furosemide — no effect on collagen synthesis marker or clinical measures.

Trust comment: Randomized, double-blind trial directly measuring collagen-synthesis biomarker but small single-center sample limits confidence.

Study Details

PMID:28891228
Participants:35
Impact:no improvement with torasemide vs furosemide (no significant change)
Trust score:3/5

trabecular bone loss (peripheral)

1 evidences

Ossein-hydroxyapatite compound (contains collagen) slowed peripheral trabecular bone loss more than calcium carbonate over 20 months in postmenopausal osteoporotic women.

Trust comment: Randomized, double-masked human trial with 40 patients and 20-month follow-up; moderate quality but small sample size.

Study Details

PMID:7703621
Participants:40
Impact:OHC: 0.8% loss vs CC: 1.8% loss over 20 months (difference ≈1.0 percentage point)
Trust score:3/5

procollagen (amniotic fluid)

1 evidences

Ancillary case–control analysis (n=166) found higher second-trimester amniotic fluid procollagen, osteopontin, IL-19 and increased positive IL-33 and TNFα in women who later had spontaneous preterm birth, especially late preterm.

Trust comment: Well-described ancillary analysis of prospectively collected trial samples with PCR-confirmed absence of bacteria and clear laboratory methods; moderate sample size and acknowledged limitations.

Study Details

PMID:36918342
Participants:166
Impact:markedly higher in late preterm births (median 663 ng/mL) vs full-term (median 17 ng/mL)
Trust score:4/5

osteopontin (amniotic fluid)

1 evidences

Ancillary case–control analysis (n=166) found higher second-trimester amniotic fluid procollagen, osteopontin, IL-19 and increased positive IL-33 and TNFα in women who later had spontaneous preterm birth, especially late preterm.

Trust comment: Well-described ancillary analysis of prospectively collected trial samples with PCR-confirmed absence of bacteria and clear laboratory methods; moderate sample size and acknowledged limitations.

Study Details

PMID:36918342
Participants:166
Impact:higher in late preterm (median 316 ng/mL) vs full-term (median 176 ng/mL)
Trust score:4/5

IL-19 (amniotic fluid)

1 evidences

Ancillary case–control analysis (n=166) found higher second-trimester amniotic fluid procollagen, osteopontin, IL-19 and increased positive IL-33 and TNFα in women who later had spontaneous preterm birth, especially late preterm.

Trust comment: Well-described ancillary analysis of prospectively collected trial samples with PCR-confirmed absence of bacteria and clear laboratory methods; moderate sample size and acknowledged limitations.

Study Details

PMID:36918342
Participants:166
Impact:higher in late preterm (median 6 ng/mL) vs full-term (median 2 ng/mL)
Trust score:4/5

IL-33 (positive test rate)

1 evidences

Ancillary case–control analysis (n=166) found higher second-trimester amniotic fluid procollagen, osteopontin, IL-19 and increased positive IL-33 and TNFα in women who later had spontaneous preterm birth, especially late preterm.

Trust comment: Well-described ancillary analysis of prospectively collected trial samples with PCR-confirmed absence of bacteria and clear laboratory methods; moderate sample size and acknowledged limitations.

Study Details

PMID:36918342
Participants:166
Impact:positive in 20.0% of late preterm vs 5.4% of full-term
Trust score:4/5

TNFα (positive test rate)

1 evidences

Ancillary case–control analysis (n=166) found higher second-trimester amniotic fluid procollagen, osteopontin, IL-19 and increased positive IL-33 and TNFα in women who later had spontaneous preterm birth, especially late preterm.

Trust comment: Well-described ancillary analysis of prospectively collected trial samples with PCR-confirmed absence of bacteria and clear laboratory methods; moderate sample size and acknowledged limitations.

Study Details

PMID:36918342
Participants:166
Impact:positive in 20.0% of late preterm vs 2.3% of full-term
Trust score:4/5

RMS20 (P-SAECG)

1 evidences

Observational cohort (n=142) showing higher baseline serum PIIINP (type III procollagen N-peptide) in patients with AF recurrence and that PIIINP independently predicted recurrence after cardioversion.

Trust comment: Moderate-sized clinical cohort with biomarker measurement and multivariable analysis, but observational design limits causal inference.

Study Details

PMID:22622138
Participants:142
Impact:RMS20 associated with PIIINP and showed significant longitudinal change in subgroup with PIIINP ~0.72 U/mL
Trust score:3/5

25(OH)D (serum)

1 evidences

Randomized double-blind trial in women >60: yogurt fortified with vitamin D3 (400 IU) and additional calcium increased 25OHD and decreased PTH and bone resorption markers over 12 weeks.

Trust comment: Randomized, double-blind design with good compliance and clear biochemical endpoints, though small completed sample size limits precision.

Study Details

PMID:25923487
Participants:48
Impact:increase D84-D0: +22.0 nmol/L (fortified) vs +6.2 nmol/L (control)
Trust score:4/5

PTH (serum)

2 evidences

Randomized double-blind trial in women >60: yogurt fortified with vitamin D3 (400 IU) and additional calcium increased 25OHD and decreased PTH and bone resorption markers over 12 weeks.

Trust comment: Randomized, double-blind design with good compliance and clear biochemical endpoints, though small completed sample size limits precision.

Study Details

PMID:25923487
Participants:48
Impact:decrease D84-D0: −16.7 ng/L (fortified) vs −2.8 ng/L (control)
Trust score:4/5

Twelve-week randomized study: calcium- and vitamin D–fortified milk (higher calcium + vitamin D + FOS-inulin) reduced bone resorption markers and PTH more than regular milk, especially in postmenopausal women.

Trust comment: Large randomized nutritional trial with clear endpoints and subgroup analyses; reasonable internal validity though short duration.

Study Details

PMID:26264387
Participants:257
Impact:reduced in most groups over time except postmenopausal control where levels increased at 12 weeks
Trust score:4/5

TRAP5b (bone resorption marker)

1 evidences

Randomized double-blind trial in women >60: yogurt fortified with vitamin D3 (400 IU) and additional calcium increased 25OHD and decreased PTH and bone resorption markers over 12 weeks.

Trust comment: Randomized, double-blind design with good compliance and clear biochemical endpoints, though small completed sample size limits precision.

Study Details

PMID:25923487
Participants:48
Impact:change D84-D0: −0.17 U/L (fortified) vs +0.25 U/L (control)
Trust score:4/5

vitamin D status (25(OH)D)

1 evidences

Twelve-week randomized study: calcium- and vitamin D–fortified milk (higher calcium + vitamin D + FOS-inulin) reduced bone resorption markers and PTH more than regular milk, especially in postmenopausal women.

Trust comment: Large randomized nutritional trial with clear endpoints and subgroup analyses; reasonable internal validity though short duration.

Study Details

PMID:26264387
Participants:257
Impact:improved in fortified milk intervention groups over 12 weeks
Trust score:4/5

CTx-1 (bone resorption)

1 evidences

Twelve-week randomized study: calcium- and vitamin D–fortified milk (higher calcium + vitamin D + FOS-inulin) reduced bone resorption markers and PTH more than regular milk, especially in postmenopausal women.

Trust comment: Large randomized nutritional trial with clear endpoints and subgroup analyses; reasonable internal validity though short duration.

Study Details

PMID:26264387
Participants:257
Impact:reduced in both pre- and postmenopausal groups; reduction significantly greater in postmenopausal fortified vs control at week 12 (P<0.035)
Trust score:4/5

aminoterminal peptide of precollagen type III (NP III)

1 evidences

Randomized study in 93 AMI patients undergoing PCI reporting that Shenfu injection (plus PCI) reduced post-AMI rise in BNP versus PCI alone and was interpreted as ameliorating myocardial injury and preventing fibrosis.

Trust comment: Randomized clinical intervention with relevant biomarkers, but limited detail and reporting in the available abstract/text reduces confidence in effect-size estimates.

Study Details

PMID:15957835
Participants:93
Impact:measured as fibrosis marker but specific numeric changes not reported in the provided summary
Trust score:3/5

Hyaluronic acid

1 evidences

Adding Korean Red Ginseng to antiviral therapy in chronic hepatitis B reduced some non‑invasive fibrosis markers (hyaluronic acid and TGF‑β) compared with antivirals alone.

Trust comment: Small, single‑center randomized trial with biomarker endpoints and single‑blinding; findings are promising but limited by size and short follow‑up.

Study Details

PMID:27603149
Participants:38
Impact:Decreased vs control (p=0.032)
Trust score:3/5

cystatin C

1 evidences

In 200 CRF patients randomized to autologous MSCs vs N-acetylcysteine, MSCs produced greater improvements in renal function markers and oxidative stress over 8 weeks.

Trust comment: Randomized study with 200 patients and multiple biochemical endpoints; good sample size though described as a pilot and limited to 8-week follow-up.

Study Details

PMID:34602393
Participants:200
Impact:decreased more with MSCs (statistically significant)
Trust score:4/5

soluble ST2

1 evidences

In >1,100 HFpEF patients sacubitril/valsartan (vs valsartan) favorably altered circulating extracellular matrix/collagen-related biomarkers at 16 weeks.

Trust comment: Large randomized trial (PARAGON-HF) with >1,100 participants and serial biomarker measurement; high sample size but biomarkers are surrogate endpoints.

Study Details

PMID:32731928
Participants:1135
Impact:−4% vs valsartan at 16 weeks (95% CI 1%–7%; p=0.002)
Trust score:4/5

Natriuretic peptide (NP) above threshold

1 evidences

In post-MI patients, eplerenone lowered a blood marker of collagen turnover (PIIINP) when baseline levels were high.

Trust comment: Randomized double-blind trial but this is a secondary analysis on ~52% subset, limiting full generalizability.

Study Details

PMID:28852839
Participants:526
Impact:Higher PIIINP associated with increased proportion of NP above thresholds (HR=1.95)
Trust score:4/5

Clinical response rate (disease activity)

1 evidences

Eight weeks of budesonide produced higher short-term clinical response and reduced lamina propria inflammatory infiltrate in collagenous colitis.

Trust comment: Double-blind RCT but small sample size and short blinded duration limit robustness.

Study Details

PMID:11781276
Participants:25
Impact:+36 percentage points (57% [8/14] budesonide vs 21% [3/14] placebo; P=0.05)
Trust score:3/5

Lamina propria inflammatory infiltrate

1 evidences

Eight weeks of budesonide produced higher short-term clinical response and reduced lamina propria inflammatory infiltrate in collagenous colitis.

Trust comment: Double-blind RCT but small sample size and short blinded duration limit robustness.

Study Details

PMID:11781276
Participants:25
Impact:Significant decrease (P<0.001)
Trust score:3/5

Collagen band thickness

1 evidences

Eight weeks of budesonide produced higher short-term clinical response and reduced lamina propria inflammatory infiltrate in collagenous colitis.

Trust comment: Double-blind RCT but small sample size and short blinded duration limit robustness.

Study Details

PMID:11781276
Participants:25
Impact:No significant change
Trust score:3/5

Procollagen I and III mRNA expression

1 evidences

Topical DHEA increased androgen receptor expression and procollagen (type I and III) mRNA in skin of postmenopausal women.

Trust comment: Randomized placebo-controlled study with biopsies and reasonable sample size supports mechanistic skin effects.

Study Details

PMID:20698844
Participants:75
Impact:Increased (dose-dependent, greater at higher DHEA doses)
Trust score:4/5

Androgen receptor (AR) expression

1 evidences

Topical DHEA increased androgen receptor expression and procollagen (type I and III) mRNA in skin of postmenopausal women.

Trust comment: Randomized placebo-controlled study with biopsies and reasonable sample size supports mechanistic skin effects.

Study Details

PMID:20698844
Participants:75
Impact:Markedly increased with DHEA treatment
Trust score:4/5

HSP47 expression

1 evidences

Topical DHEA increased androgen receptor expression and procollagen (type I and III) mRNA in skin of postmenopausal women.

Trust comment: Randomized placebo-controlled study with biopsies and reasonable sample size supports mechanistic skin effects.

Study Details

PMID:20698844
Participants:75
Impact:Increased, especially at highest DHEA doses
Trust score:4/5

Basal serum parathormone (PTH)

1 evidences

Twelve months of high-impact exercise lowered basal serum PTH but did not change bone turnover markers in premenopausal women.

Trust comment: Well-powered randomized controlled exercise trial with objective hormonal measures and clear PTH effect.

Study Details

PMID:19262975
Participants:120
Impact:Decreased more in exercise group (-11.2 pg/mL) vs control (-2.2 pg/mL); P=0.03
Trust score:4/5

TRACP5b (bone resorption marker)

1 evidences

Twelve months of high-impact exercise lowered basal serum PTH but did not change bone turnover markers in premenopausal women.

Trust comment: Well-powered randomized controlled exercise trial with objective hormonal measures and clear PTH effect.

Study Details

PMID:19262975
Participants:120
Impact:No persistent change
Trust score:4/5

Serum sRAGE

1 evidences

All patients received vitamin D3 and calcium; HRT (vs no HRT) decreased serum sRAGE and associated with increased BMD and reduced bone/cartilage turnover.

Trust comment: Randomized controlled trial with 2-year follow-up showing consistent biochemical and BMD associations, though mechanistic causality is indirect.

Study Details

PMID:19416946
Participants:88
Impact:Decreased at 1 and 2 years with HRT (vs baseline)
Trust score:4/5

Bone mineral density (total BMD)

1 evidences

All patients received vitamin D3 and calcium; HRT (vs no HRT) decreased serum sRAGE and associated with increased BMD and reduced bone/cartilage turnover.

Trust comment: Randomized controlled trial with 2-year follow-up showing consistent biochemical and BMD associations, though mechanistic causality is indirect.

Study Details

PMID:19416946
Participants:88
Impact:Increased in association with sRAGE decline after 2 years
Trust score:4/5

Bone/cartilage turnover markers (e.g., C-terminal propeptide of type I procollagen, CTX, COMP)

1 evidences

All patients received vitamin D3 and calcium; HRT (vs no HRT) decreased serum sRAGE and associated with increased BMD and reduced bone/cartilage turnover.

Trust comment: Randomized controlled trial with 2-year follow-up showing consistent biochemical and BMD associations, though mechanistic causality is indirect.

Study Details

PMID:19416946
Participants:88
Impact:Concentrations diminished in parallel with sRAGE decline
Trust score:4/5

total effective rate (CR+PR)

1 evidences

Randomized study in NSCLC patients found recombinant human endostatin (a collagen-derived fragment) given during a normalization window with radiotherapy increased response rates and median survival versus radiotherapy alone, but did not significantly improve long-term overall survival.

Trust comment: Human randomized trial of a collagen-derived therapeutic (endostatin) with modest sample size and positive short-term outcomes but limited long-term survival benefit.

Study Details

PMID:22099051
Participants:50
Impact:80% with RHES+radiotherapy vs 44% with radiotherapy alone (P = 0.009; +36 percentage points)
Trust score:3/5

median survival

1 evidences

Randomized study in NSCLC patients found recombinant human endostatin (a collagen-derived fragment) given during a normalization window with radiotherapy increased response rates and median survival versus radiotherapy alone, but did not significantly improve long-term overall survival.

Trust comment: Human randomized trial of a collagen-derived therapeutic (endostatin) with modest sample size and positive short-term outcomes but limited long-term survival benefit.

Study Details

PMID:22099051
Participants:50
Impact:21.1 ± 0.97 months vs 16.5 ± 0.95 months (+4.6 months, P = 0.004)
Trust score:3/5

local control rates

1 evidences

Randomized study in NSCLC patients found recombinant human endostatin (a collagen-derived fragment) given during a normalization window with radiotherapy increased response rates and median survival versus radiotherapy alone, but did not significantly improve long-term overall survival.

Trust comment: Human randomized trial of a collagen-derived therapeutic (endostatin) with modest sample size and positive short-term outcomes but limited long-term survival benefit.

Study Details

PMID:22099051
Participants:50
Impact:Improved 1- and 2-year local control with RHES (statistically significant, P < 0.05)
Trust score:3/5

Subjective Frey's syndrome incidence

1 evidences

Bovine pericardial membrane placed after parotidectomy reduced Frey's syndrome compared with SMAS flap at 12-month follow-up.

Trust comment: Direct collagenous membrane intervention in humans but small pilot sample (n=40) and limited power; study design details limited.

Study Details

PMID:23467957
Participants:40
Impact:5% in collagen-membrane group vs 10% in control (−5 percentage points)
Trust score:3/5

Objective Frey's syndrome (Minor's/starch-iodine test)

1 evidences

Bovine pericardial membrane placed after parotidectomy reduced Frey's syndrome compared with SMAS flap at 12-month follow-up.

Trust comment: Direct collagenous membrane intervention in humans but small pilot sample (n=40) and limited power; study design details limited.

Study Details

PMID:23467957
Participants:40
Impact:0 cases in collagen-membrane group vs 2 cases (10%) in control (−10 percentage points)
Trust score:3/5

hospital stay

1 evidences

Application of a fibrinogen/thrombin-coated collagen patch did not significantly reduce clinically relevant pancreatic fistulas or hospital stay.

Trust comment: Randomized clinical trial directly tested a collagen patch but was single-center and may be underpowered for some outcomes.

Study Details

PMID:31502003
Participants:124
Impact:Intervention 11.6 days vs control 12.1 days (no significant difference, p=0.585)
Trust score:3/5

Pulp sensibility (cold test)

1 evidences

Randomized trial of 36 necrotic teeth using four scaffolds (periapical bleeding, PRF, collagen, hydroxyapatite); collagen scaffold showed intermediate rates of cold-test sensibility recovery and all groups had good radiographic periapical healing at 12 months.

Trust comment: Randomised clinical trial but small sample (n=36 teeth total, n=9 per arm) and some outcomes non-significant.

Study Details

PMID:34810392
Participants:36
Impact:44.4% positive in collagen group at 12 months (group-level outcome; between-group differences non-significant)
Trust score:3/5

Pulp sensibility at earlier timepoints (3–9 months)

1 evidences

Randomized trial of 36 necrotic teeth using four scaffolds (periapical bleeding, PRF, collagen, hydroxyapatite); collagen scaffold showed intermediate rates of cold-test sensibility recovery and all groups had good radiographic periapical healing at 12 months.

Trust comment: Randomised clinical trial but small sample (n=36 teeth total, n=9 per arm) and some outcomes non-significant.

Study Details

PMID:34810392
Participants:36
Impact:11.15% at 3–6 months; 33.3% at 9 months (collagen group)
Trust score:3/5

vertical alveolar bone level change

1 evidences

Use of Bio‑Oss Collagen with early implant placement (8–10 weeks) preserved alveolar bone levels better than collagen alone or no treatment.

Trust comment: Small clinical study with clear radiographic endpoints but limited sample size and group sizes; not randomized.

Study Details

PMID:22244384
Participants:25
Impact:significantly less vs untreated control (p<0.001)
Trust score:3/5

annual rate of bone level change

1 evidences

Use of Bio‑Oss Collagen with early implant placement (8–10 weeks) preserved alveolar bone levels better than collagen alone or no treatment.

Trust comment: Small clinical study with clear radiographic endpoints but limited sample size and group sizes; not randomized.

Study Details

PMID:22244384
Participants:25
Impact:significantly lower for Bio‑Oss Collagen + implant vs control (p=0.019) and vs collagen alone (p=0.003)
Trust score:3/5

knee flexion range of motion (ROM)

1 evidences

In athletes with early knee arthritis, 12 weeks of collagen supplementation reduced pain from baseline but was not superior to exercise; combined collagen+exercise improved several functional outcomes.

Trust comment: Quasi‑randomized, blinded trial with modest sample size and short (12‑week) collagen exposure limiting long‑term conclusions.

Study Details

PMID:38063519
Participants:48
Impact:improved in combined and exercise-only groups (p<0.001); not significant in collagen-only (p=0.111)
Trust score:3/5

postoperative drainage volume (first 24 h)

1 evidences

Randomized trial found collagen hemostatic sponge reduced postoperative drainage volume and calculated drainage blood compared with gelatin sponge in posterior lumbar fusion.

Trust comment: Randomized controlled design with adequate sample size and objective outcomes supports moderate–high trustworthiness.

Study Details

PMID:27955644
Participants:92
Impact:significantly lower for collagen sponge vs gelatin (p<0.05)
Trust score:4/5

total postoperative drainage volume

1 evidences

Randomized trial found collagen hemostatic sponge reduced postoperative drainage volume and calculated drainage blood compared with gelatin sponge in posterior lumbar fusion.

Trust comment: Randomized controlled design with adequate sample size and objective outcomes supports moderate–high trustworthiness.

Study Details

PMID:27955644
Participants:92
Impact:significantly lower for collagen sponge vs gelatin (p<0.05)
Trust score:4/5

drainage blood volume (ml)

1 evidences

Randomized trial found collagen hemostatic sponge reduced postoperative drainage volume and calculated drainage blood compared with gelatin sponge in posterior lumbar fusion.

Trust comment: Randomized controlled design with adequate sample size and objective outcomes supports moderate–high trustworthiness.

Study Details

PMID:27955644
Participants:92
Impact:lower in collagen and Stypro groups vs gelatin; no difference between collagen and Stypro
Trust score:4/5

time to full healing

1 evidences

In a randomized trial of diabetic foot ulcers, collagen dressings had longer median time-to-heal and lower 12‑week healing rates than PLA matrices.

Trust comment: Randomized single‑center trial but small sample size limits generalizability; outcomes clinically meaningful.

Study Details

PMID:37643451
Participants:30
Impact:median 14.8 weeks (collagen) vs 9.3 weeks (PLA), P=0.021 (collagen slower)
Trust score:3/5

proportion healed at 12 weeks

1 evidences

In a randomized trial of diabetic foot ulcers, collagen dressings had longer median time-to-heal and lower 12‑week healing rates than PLA matrices.

Trust comment: Randomized single‑center trial but small sample size limits generalizability; outcomes clinically meaningful.

Study Details

PMID:37643451
Participants:30
Impact:33% healed (collagen) vs 80% healed (PLA), P=0.025
Trust score:3/5

Global Assessment Score (GAS) at 12 weeks

1 evidences

Adding an oral supplement containing hydrolysed marine collagen plus amino acids and micronutrients to standard hair-loss treatments improved blinded clinician-rated hair outcomes over 12 weeks versus treatments alone and was well tolerated.

Trust comment: Randomized, assessor-blinded multicenter trial with 83 enrolled (76 completers); not double-blind and authors declare COI, but outcomes and analysis are reasonable.

Study Details

PMID:37357646
Participants:76
Impact:mean difference +1.01 (1.67 vs 0.66) favoring supplement (95% CI 0.52–1.50)
Trust score:4/5

proportion with GAS≥0

1 evidences

Adding an oral supplement containing hydrolysed marine collagen plus amino acids and micronutrients to standard hair-loss treatments improved blinded clinician-rated hair outcomes over 12 weeks versus treatments alone and was well tolerated.

Trust comment: Randomized, assessor-blinded multicenter trial with 83 enrolled (76 completers); not double-blind and authors declare COI, but outcomes and analysis are reasonable.

Study Details

PMID:37357646
Participants:76
Impact:85.4% vs 48.6% (absolute +36.8 percentage points) favoring supplement
Trust score:4/5

clinically meaningful response (GAS≥2)

1 evidences

Adding an oral supplement containing hydrolysed marine collagen plus amino acids and micronutrients to standard hair-loss treatments improved blinded clinician-rated hair outcomes over 12 weeks versus treatments alone and was well tolerated.

Trust comment: Randomized, assessor-blinded multicenter trial with 83 enrolled (76 completers); not double-blind and authors declare COI, but outcomes and analysis are reasonable.

Study Details

PMID:37357646
Participants:76
Impact:50% vs 23% (absolute +27 percentage points) favoring supplement
Trust score:4/5

scar severity score improvement

1 evidences

Both percutaneous collagen induction and focal 100% TCA (CROSS) improved atrophic acne scars substantially; no significant difference between the two methods.

Trust comment: Randomized small trial (n=30) showing both treatments effective, but limited by small sample size.

Study Details

PMID:21269351
Participants:30
Impact:PCI mean improvement 68.3%; TCA CROSS mean improvement 75.3%; difference not significant (p=0.47)
Trust score:3/5

Ridge width/height

1 evidences

Randomized clinical study (60 patients) comparing PRF, PRF+collagen plug, and control after tooth extraction; evaluated ridge dimensions and postoperative pain.

Trust comment: Prospective randomized human trial (n=60) with objective measurements and CBCT; moderate–high quality though sample size modest and short follow-up (3 months).

Study Details

PMID:39064496
Participants:60
Impact:No significant change in ridge width or height vs control (p>0.05)
Trust score:4/5

Keratinized mucosa width gain

1 evidences

Randomized clinical trial (63 enrolled, 58 available for follow-up) comparing apically positioned flap, free gingival graft (FGG), and a collagen matrix to increase keratinized mucosa before implant prosthesis; outcomes at 4 weeks.

Trust comment: Randomized parallel-group human trial with objective measures and reasonable follow-up; moderate quality though some dropouts and short-term endpoint.

Study Details

PMID:32159530
Participants:58
Impact:Collagen matrix group: 3.03 ± 0.58 mm gain at 4 weeks (FGG 4.85 ± 1.11 mm; control 1.93 ± 0.85 mm)
Trust score:4/5

skin hydration (moisture)

1 evidences

Topical meristem-cell-based serums applied for 4 weeks improved skin hydration, elasticity and increased dermal collagen markers (hydroxyproline) with reduced lipid peroxidation.

Trust comment: Randomized single-blind trial with objective instrumental and biochemical measures but no placebo control and small biopsy subgroup (n=12) for collagen marker.

Study Details

PMID:39334942
Participants:102
Impact:statistically significant improvement after 4 weeks
Trust score:3/5

dermal collagen content (hydroxyproline & dermal thickness/density)

1 evidences

Topical meristem-cell-based serums applied for 4 weeks improved skin hydration, elasticity and increased dermal collagen markers (hydroxyproline) with reduced lipid peroxidation.

Trust comment: Randomized single-blind trial with objective instrumental and biochemical measures but no placebo control and small biopsy subgroup (n=12) for collagen marker.

Study Details

PMID:39334942
Participants:102
Impact:significant increase (hydroxyproline p<0.0068; ultrasonic dermal density/thickness improved)
Trust score:3/5

new bone area (%NB)

1 evidences

Compared collagen-stabilized bovine bone (ABBM-C) to composite graft (ABBM+autogenous bone) for sinus augmentation; similar new bone but ABBM-C showed lower osseointegration and less mature bone in some zones.

Trust comment: Prospective clinical trial with objective histomorphometric outcomes and moderate sample size, though some subgroup differences and limited sample per ROI.

Study Details

PMID:26374171
Participants:40
Impact:no significant difference between ABBM-C and ABBM+AB
Trust score:4/5

graft osseointegration (%OI, ROI-2)

1 evidences

Compared collagen-stabilized bovine bone (ABBM-C) to composite graft (ABBM+autogenous bone) for sinus augmentation; similar new bone but ABBM-C showed lower osseointegration and less mature bone in some zones.

Trust comment: Prospective clinical trial with objective histomorphometric outcomes and moderate sample size, though some subgroup differences and limited sample per ROI.

Study Details

PMID:26374171
Participants:40
Impact:test 19.6% vs control 42.0% (−22.4 percentage points, P<0.05)
Trust score:4/5

lamellar-to-woven bone ratio

1 evidences

Compared collagen-stabilized bovine bone (ABBM-C) to composite graft (ABBM+autogenous bone) for sinus augmentation; similar new bone but ABBM-C showed lower osseointegration and less mature bone in some zones.

Trust comment: Prospective clinical trial with objective histomorphometric outcomes and moderate sample size, though some subgroup differences and limited sample per ROI.

Study Details

PMID:26374171
Participants:40
Impact:test 0.38 vs control 1.22 (lower in test, P<0.05)
Trust score:4/5

symptomatic lymphocele incidence

1 evidences

Multicenter randomized trial: intraoperative collagen-fibrin patch did not reduce symptomatic or asymptomatic lymphocele rates after pelvic lymphadenectomy.

Trust comment: Adequately powered multicenter randomized trial with clear clinical endpoints and complete follow-up.

Study Details

PMID:29395308
Participants:164
Impact:intervention 7.4% (5/68) vs control 3.5% (3/85); no significant reduction (P=0.47)
Trust score:4/5

asymptomatic lymphocele incidence

1 evidences

Multicenter randomized trial: intraoperative collagen-fibrin patch did not reduce symptomatic or asymptomatic lymphocele rates after pelvic lymphadenectomy.

Trust comment: Adequately powered multicenter randomized trial with clear clinical endpoints and complete follow-up.

Study Details

PMID:29395308
Participants:164
Impact:intervention 23.5% vs control 21.2% (P=0.85)
Trust score:4/5

cell area fraction on abutment surface

1 evidences

Randomized triple-blind trial: plasma (argon) cleaning of titanium abutments increased cell-covered area, altered collagen fiber density/orientation, and reduced contamination versus untreated abutments.

Trust comment: Triple-blinded RCT with objective histology but small sample and some outcomes only trend-level significant.

Study Details

PMID:27552929
Participants:30
Impact:33.75% (plasma) vs 15.14% (control); +18.61 percentage points (P=0.089, trend)
Trust score:3/5

surface contamination

1 evidences

Randomized triple-blind trial: plasma (argon) cleaning of titanium abutments increased cell-covered area, altered collagen fiber density/orientation, and reduced contamination versus untreated abutments.

Trust comment: Triple-blinded RCT with objective histology but small sample and some outcomes only trend-level significant.

Study Details

PMID:27552929
Participants:30
Impact:reduced in plasma group (no contamination cases in plasma group; P=0.006)
Trust score:3/5

ridge width gain at crest (0 mm)

1 evidences

RCT comparing FDBA + collagen membrane versus combined FDBA+autogenous bone + collagen membrane for horizontal ridge augmentation: both produced significant ridge width gains with no difference in new bone amount or connective tissue.

Trust comment: Randomized controlled trial with radiologic and histologic endpoints and adequate reporting; moderate sample size.

Study Details

PMID:32902105
Participants:42
Impact:FDBA + collagen: +2.78 ± 1.44 mm vs combined: +2.40 ± 1.60 mm (both significant vs baseline)
Trust score:4/5

new bone amount

1 evidences

RCT comparing FDBA + collagen membrane versus combined FDBA+autogenous bone + collagen membrane for horizontal ridge augmentation: both produced significant ridge width gains with no difference in new bone amount or connective tissue.

Trust comment: Randomized controlled trial with radiologic and histologic endpoints and adequate reporting; moderate sample size.

Study Details

PMID:32902105
Participants:42
Impact:no significant difference between groups (P=0.367)
Trust score:4/5

analgesic/NSAID consumption

1 evidences

After HA injection, adding an oral collagen-containing viscosupplement tended to improve symptoms and reduced patients' use of painkillers more than HA alone.

Trust comment: Randomized double-blind placebo-controlled trial with 100 patients, but the oral product combined multiple ingredients so effects cannot be attributed solely to collagen.

Study Details

PMID:26550817
Participants:100
Impact:significantly reduced with oral collagen-containing formulation (reported significant)
Trust score:4/5

Esophageal stenosis rate

1 evidences

Glucocorticoid (oral ± local injection) treatment after esophageal ESD reduced post‑operative stenosis and lowered TGF‑β1 and collagen‑I expression in mucosal tissue.

Trust comment: Prospective randomized clinical study (n=81) with clear clinical and molecular endpoints; moderate sample size.

Study Details

PMID:35692065
Participants:81
Impact:Control 82.6% vs oral prednisone 46.4% vs oral+local 20.0% (lower with glucocorticoids)
Trust score:4/5

Collagen‑I protein expression

1 evidences

Glucocorticoid (oral ± local injection) treatment after esophageal ESD reduced post‑operative stenosis and lowered TGF‑β1 and collagen‑I expression in mucosal tissue.

Trust comment: Prospective randomized clinical study (n=81) with clear clinical and molecular endpoints; moderate sample size.

Study Details

PMID:35692065
Participants:81
Impact:Decreased (glucocorticoid groups showed reduced collagen‑I expression vs control)
Trust score:4/5

TGF‑β1 expression

1 evidences

Glucocorticoid (oral ± local injection) treatment after esophageal ESD reduced post‑operative stenosis and lowered TGF‑β1 and collagen‑I expression in mucosal tissue.

Trust comment: Prospective randomized clinical study (n=81) with clear clinical and molecular endpoints; moderate sample size.

Study Details

PMID:35692065
Participants:81
Impact:Decreased (glucocorticoid groups showed reduced TGF‑β1 expression vs control)
Trust score:4/5

Plaque echogenicity (GSM)

1 evidences

TTFCA treatment (60 mg TID) for 12 months increased femoral plaque echogenicity (GSM) and homogeneity, consistent with increased collagen/stroma within plaques and plaque stabilization.

Trust comment: Randomized, placebo‑controlled human trial with 12‑month follow‑up but modest sample size and partial attrition.

Study Details

PMID:11666127
Participants:50
Impact:Treatment GSM increased from 14.0 to 22.8 vs controls 14.3 to 15.0 (approx +8.8 units in treatment)
Trust score:4/5

Plaque size change

1 evidences

TTFCA treatment (60 mg TID) for 12 months increased femoral plaque echogenicity (GSM) and homogeneity, consistent with increased collagen/stroma within plaques and plaque stabilization.

Trust comment: Randomized, placebo‑controlled human trial with 12‑month follow‑up but modest sample size and partial attrition.

Study Details

PMID:11666127
Participants:50
Impact:Controls median size increase 23% (0–44%) vs treatment unchanged (variation ~7%)
Trust score:4/5

Plaque homogeneity / inferred collagen content

1 evidences

TTFCA treatment (60 mg TID) for 12 months increased femoral plaque echogenicity (GSM) and homogeneity, consistent with increased collagen/stroma within plaques and plaque stabilization.

Trust comment: Randomized, placebo‑controlled human trial with 12‑month follow‑up but modest sample size and partial attrition.

Study Details

PMID:11666127
Participants:50
Impact:Qualitative increase in homogeneity and inferred collagen (treatment showed increased stromal/collagen features)
Trust score:4/5

Modified Vancouver Scar Scale (mVSS)

1 evidences

Both microneedling and fractional CO2 laser improved scar clinical scores and histochemical collagen/elastin; fractional CO2 laser produced larger increases in collagen (neocollagenesis).

Trust comment: Small randomized clinical study (n=30) with histochemical endpoints; limited by small sample size.

Study Details

PMID:34468410
Participants:30
Impact:Improved in both treatment arms (clinical scar scores decreased)
Trust score:3/5

Collagen content (histochemical)

1 evidences

Both microneedling and fractional CO2 laser improved scar clinical scores and histochemical collagen/elastin; fractional CO2 laser produced larger increases in collagen (neocollagenesis).

Trust comment: Small randomized clinical study (n=30) with histochemical endpoints; limited by small sample size.

Study Details

PMID:34468410
Participants:30
Impact:Increased after both treatments; greater percentage increase with fractional CO2 laser than microneedling
Trust score:3/5

Collagen amount (biopsy)

1 evidences

Adding topical PRP to fractional laser improved patient satisfaction, increased skin elasticity, collagen amount, and fibroblast number on biopsy compared with laser alone.

Trust comment: Small controlled clinical study (n=22) with biopsy and objective skin measures but limited sample size.

Study Details

PMID:22288389
Participants:22
Impact:Increased with PRP + fractional laser versus fractional laser alone
Trust score:3/5

Fibroblast number

1 evidences

Adding topical PRP to fractional laser improved patient satisfaction, increased skin elasticity, collagen amount, and fibroblast number on biopsy compared with laser alone.

Trust comment: Small controlled clinical study (n=22) with biopsy and objective skin measures but limited sample size.

Study Details

PMID:22288389
Participants:22
Impact:Increased after PRP combined with fractional laser
Trust score:3/5

Griffith aging score

1 evidences

40 women randomized; treated group (Giovina supplement) over 4 months showed lower clinical aging score, reduced skin redness, and fewer visible wrinkles than controls.

Trust comment: Randomized single-blind pilot with objective imaging endpoints but small, single-sex sample and borderline significance for some outcomes.

Study Details

PMID:40411804
Participants:40
Impact:-0.7 points (4.5 → 3.8, p=0.001)
Trust score:3/5

Erythema (Redspot extent)

1 evidences

40 women randomized; treated group (Giovina supplement) over 4 months showed lower clinical aging score, reduced skin redness, and fewer visible wrinkles than controls.

Trust comment: Randomized single-blind pilot with objective imaging endpoints but small, single-sex sample and borderline significance for some outcomes.

Study Details

PMID:40411804
Participants:40
Impact:-~17% (Redspot_Abs 15500.07 → 12848.79, p=0.004)
Trust score:3/5

Visible wrinkle count

1 evidences

40 women randomized; treated group (Giovina supplement) over 4 months showed lower clinical aging score, reduced skin redness, and fewer visible wrinkles than controls.

Trust comment: Randomized single-blind pilot with objective imaging endpoints but small, single-sex sample and borderline significance for some outcomes.

Study Details

PMID:40411804
Participants:40
Impact:-23% (Wrinkle_count 50.33 → 38.53; p=0.059)
Trust score:3/5

Postoperative pain scores

1 evidences

60 patients randomized; primary closure over a gentamicin-impregnated collagen sponge led to less pain, faster healing, and lower overall cost than open excision, with similar 5-year recurrence.

Trust comment: Randomized clinical trial (n=60) directly uses a collagen-containing implant with 5-year follow-up; older study but clinically relevant endpoints.

Study Details

PMID:19823853
Participants:60
Impact:Lower in closed-with-collagen group (significant across early post-op days)
Trust score:4/5

Healing rate at 4 weeks

1 evidences

60 patients randomized; primary closure over a gentamicin-impregnated collagen sponge led to less pain, faster healing, and lower overall cost than open excision, with similar 5-year recurrence.

Trust comment: Randomized clinical trial (n=60) directly uses a collagen-containing implant with 5-year follow-up; older study but clinically relevant endpoints.

Study Details

PMID:19823853
Participants:60
Impact:Higher proportion healed in closed-with-collagen group (significant)
Trust score:4/5

Recurrence at 5 years

1 evidences

60 patients randomized; primary closure over a gentamicin-impregnated collagen sponge led to less pain, faster healing, and lower overall cost than open excision, with similar 5-year recurrence.

Trust comment: Randomized clinical trial (n=60) directly uses a collagen-containing implant with 5-year follow-up; older study but clinically relevant endpoints.

Study Details

PMID:19823853
Participants:60
Impact:No difference (recurrence rates similar between groups)
Trust score:4/5

healing complications (exposure/infection)

1 evidences

In this randomized trial, covering customized titanium mesh with a resorbable (cross-linked collagen) membrane tended to reduce healing complications and improve regenerated bone volume compared with mesh alone, though differences were not statistically significant.

Trust comment: - Checklist: - Confirm whether study tests Collagen effect on humans and list top outcomes. - Determine participant count (completed subjects). - Rate study quality (1–5) with brief justification. - Report quantitative change per outcome and give a very short plain-language summary. Justification: This is a randomized, investigator-blinded clinical trial directly testing the effect of adding a resorbable collagen membrane (vs no membrane) with objective measures; good design but small sample (n=30) and many outcomes were not statistically significant, so moderate-high trust (4).

Study Details

PMID:34551168
Participants:30
Impact:decreased from 33.3% (mesh alone) to 13.3% (mesh + collagen membrane) (−20 percentage points, NS)
Trust score:4/5

regeneration rate (RR)

1 evidences

In this randomized trial, covering customized titanium mesh with a resorbable (cross-linked collagen) membrane tended to reduce healing complications and improve regenerated bone volume compared with mesh alone, though differences were not statistically significant.

Trust comment: - Checklist: - Confirm whether study tests Collagen effect on humans and list top outcomes. - Determine participant count (completed subjects). - Rate study quality (1–5) with brief justification. - Report quantitative change per outcome and give a very short plain-language summary. Justification: This is a randomized, investigator-blinded clinical trial directly testing the effect of adding a resorbable collagen membrane (vs no membrane) with objective measures; good design but small sample (n=30) and many outcomes were not statistically significant, so moderate-high trust (4).

Study Details

PMID:34551168
Participants:30
Impact:increased from 74.3% to 82.3% (+8.0 percentage points, NS)
Trust score:4/5

LV remodeling

1 evidences

In post-MI patients, measures of collagen-related biomarkers one month after MI predicted adverse LV remodeling and higher cardiovascular events over follow-up.

Trust comment: Prospective multicenter human study with biomarker measurements (n=218) and multivariate analysis; moderate-to-high quality for prognostic associations.

Study Details

PMID:23983248
Participants:218
Impact:+86% odds (OR 1.86, P=0.043) associated with low type III procollagen/type I telopeptide ratio (≤1)
Trust score:4/5

BNP >100 pg/mL

1 evidences

In post-MI patients, measures of collagen-related biomarkers one month after MI predicted adverse LV remodeling and higher cardiovascular events over follow-up.

Trust comment: Prospective multicenter human study with biomarker measurements (n=218) and multivariate analysis; moderate-to-high quality for prognostic associations.

Study Details

PMID:23983248
Participants:218
Impact:+135% odds (OR 2.35, P=0.006) of adverse LV remodeling
Trust score:4/5

Composite cardiovascular events (death or HF hospitalization)

1 evidences

In post-MI patients, measures of collagen-related biomarkers one month after MI predicted adverse LV remodeling and higher cardiovascular events over follow-up.

Trust comment: Prospective multicenter human study with biomarker measurements (n=218) and multivariate analysis; moderate-to-high quality for prognostic associations.

Study Details

PMID:23983248
Participants:218
Impact:Higher event burden (14 events/216 patients), significant (P=0.0001)
Trust score:4/5

Total treatment time

1 evidences

Randomized clinical trial (nested) in orthodontic patients: decortication and porcine 3D collagen matrix tended to shorten alignment/total treatment times, while IL‑1β allele 2 had no clear effect.

Trust comment: Small randomized clinical study (n=37 completed) with objective timing outcomes; limited power and several non-significant comparisons.

Study Details

PMID:32952230
Participants:37
Impact:Group 3 −27% and Group 4 −35% vs control (faster), differences not statistically significant
Trust score:3/5

Upper arch alignment time

1 evidences

Randomized clinical trial (nested) in orthodontic patients: decortication and porcine 3D collagen matrix tended to shorten alignment/total treatment times, while IL‑1β allele 2 had no clear effect.

Trust comment: Small randomized clinical study (n=37 completed) with objective timing outcomes; limited power and several non-significant comparisons.

Study Details

PMID:32952230
Participants:37
Impact:Decortication group (Group 2) reduced upper arch time from 179.2 to 98.8 days (~−45%), P=0.01
Trust score:3/5

IL‑1β allele 2 presence

1 evidences

Randomized clinical trial (nested) in orthodontic patients: decortication and porcine 3D collagen matrix tended to shorten alignment/total treatment times, while IL‑1β allele 2 had no clear effect.

Trust comment: Small randomized clinical study (n=37 completed) with objective timing outcomes; limited power and several non-significant comparisons.

Study Details

PMID:32952230
Participants:37
Impact:No significant effect on treatment time (no clear difference)
Trust score:3/5

ECCA score (scar severity)

1 evidences

Split-face RCT in humans found both MFR+topical insulin and MFR+placebo significantly improved acne scars and scar volume; insulin produced earlier improvement but final outcomes were similar between sides.

Trust comment: Well-designed split-face double-blind RCT (n=29 completed) with objective 3D imaging and clinical grading; limited sample size but robust within-subject design.

Study Details

PMID:39970082
Participants:29
Impact:Reduced by 46.77% (TI) and 46.39% (placebo); no between-group difference (p=0.728)
Trust score:4/5

Atrophic scar volume

1 evidences

Split-face RCT in humans found both MFR+topical insulin and MFR+placebo significantly improved acne scars and scar volume; insulin produced earlier improvement but final outcomes were similar between sides.

Trust comment: Well-designed split-face double-blind RCT (n=29 completed) with objective 3D imaging and clinical grading; limited sample size but robust within-subject design.

Study Details

PMID:39970082
Participants:29
Impact:TI: 18.22→13.48 mm³ (−26%); Placebo: 18.02→14.03 mm³ (−22%); between-group p=0.517
Trust score:4/5

tendon collagen organization (biopsy)

1 evidences

Randomized double-blind trial comparing isolated bioinductive repair (implant that induces collagen deposition) versus sutured repair for small/medium full-thickness rotator cuff tears: bioinductive repair yielded superior collagen organization, greater tendon thickness increase, 100% MRI healing at 12/24 months, better PROs and faster return to work.

Trust comment: Well-conducted randomized, double-blind RCT with meaningful objective (biopsy, MRI) and patient-reported outcomes; single-center but adequate sample (n=60).

Study Details

PMID:38734130
Participants:60
Impact:markedly improved (all IBR patients had highly organized parallel collagen vs 24/30 controls with poorly organized fibers)
Trust score:4/5

healing on MRI

1 evidences

Randomized double-blind trial comparing isolated bioinductive repair (implant that induces collagen deposition) versus sutured repair for small/medium full-thickness rotator cuff tears: bioinductive repair yielded superior collagen organization, greater tendon thickness increase, 100% MRI healing at 12/24 months, better PROs and faster return to work.

Trust comment: Well-conducted randomized, double-blind RCT with meaningful objective (biopsy, MRI) and patient-reported outcomes; single-center but adequate sample (n=60).

Study Details

PMID:38734130
Participants:60
Impact:100% healing in IBR group at 12 and 24 months
Trust score:4/5

sternal wound infection rate

1 evidences

Randomized study of gentamicin-collagen implant vs control in CABG patients showed a small, nonsignificant reduction in sternal wound infections and mediastinitis with the implant; treatment was safe.

Trust comment: Large randomized trial with objective clinical endpoints, but effect was small and not statistically significant and authors note limited power for definitive conclusions.

Study Details

PMID:15620444
Participants:542
Impact:4.0% (implant) vs 5.9% (control); absolute reduction ~1.9 percentage points (not statistically significant)
Trust score:3/5

total and appendicular lean mass

1 evidences

In older men doing home-based resistance exercise, obesity/metabolic risk reduced anabolic response; a higher-quality multi-ingredient supplement (which included calcium) produced better lean-mass, strength and bone marker outcomes than a lower-quality supplement.

Trust comment: Based on a randomized, double-blind trial but current report is a retrospective analysis with modest sample size (32 completers) and subgroup comparisons (n=20) limiting power.

Study Details

PMID:39771028
Participants:32
Impact:marginal decrease in collagen-peptide (PLA) group; moderate increase in high-quality MIS group
Trust score:4/5

fat mass / % body fat

1 evidences

In older men doing home-based resistance exercise, obesity/metabolic risk reduced anabolic response; a higher-quality multi-ingredient supplement (which included calcium) produced better lean-mass, strength and bone marker outcomes than a lower-quality supplement.

Trust comment: Based on a randomized, double-blind trial but current report is a retrospective analysis with modest sample size (32 completers) and subgroup comparisons (n=20) limiting power.

Study Details

PMID:39771028
Participants:32
Impact:increase (significant) in collagen-peptide (PLA) group; marginal loss in high-quality MIS group
Trust score:4/5

strength

1 evidences

In older men doing home-based resistance exercise, obesity/metabolic risk reduced anabolic response; a higher-quality multi-ingredient supplement (which included calcium) produced better lean-mass, strength and bone marker outcomes than a lower-quality supplement.

Trust comment: Based on a randomized, double-blind trial but current report is a retrospective analysis with modest sample size (32 completers) and subgroup comparisons (n=20) limiting power.

Study Details

PMID:39771028
Participants:32
Impact:no significant improvement in collagen-peptide group vs significant improvements in high-quality MIS group
Trust score:4/5

probing pocket depth reduction

1 evidences

Proof-of-principle randomized study of collagen scaffolds with/without autologous BM-MSCs for periodontal defects: all treatments led to significant clinical improvements over 12 months with no adverse healing events; radiographic bone fill was less in scaffold-only group.

Trust comment: Small, randomized proof-of-principle trial using collagen scaffolds; clinically meaningful outcomes but limited sample size and defect-based randomization.

Study Details

PMID:33899259
Participants:27
Impact:−3.7 mm (estimated marginal mean at 12 months)
Trust score:3/5

radiographic bone fill (CEJ-BD reduction)

1 evidences

Proof-of-principle randomized study of collagen scaffolds with/without autologous BM-MSCs for periodontal defects: all treatments led to significant clinical improvements over 12 months with no adverse healing events; radiographic bone fill was less in scaffold-only group.

Trust comment: Small, randomized proof-of-principle trial using collagen scaffolds; clinically meaningful outcomes but limited sample size and defect-based randomization.

Study Details

PMID:33899259
Participants:27
Impact:greater reduction in cell-based and surgical groups vs scaffold-only (p < .023)
Trust score:3/5

bone formation markers (osteocalcin, PICP, ALP)

1 evidences

Steroid pulses altered bone turnover markers; adding alendronate reduced steroid-induced bone resorption.

Trust comment: Moderate-quality clinical study with randomized allocation in reduced BMD subgroup but modest sample size and biomarker-focused outcomes.

Study Details

PMID:22728519
Participants:73
Impact:decreased after methylprednisolone
Trust score:3/5

bone resorption markers (ICTP, CTX, urinary deoxypyridinoline)

1 evidences

Steroid pulses altered bone turnover markers; adding alendronate reduced steroid-induced bone resorption.

Trust comment: Moderate-quality clinical study with randomized allocation in reduced BMD subgroup but modest sample size and biomarker-focused outcomes.

Study Details

PMID:22728519
Participants:73
Impact:increased after methylprednisolone
Trust score:3/5

bone resorption with alendronate

1 evidences

Steroid pulses altered bone turnover markers; adding alendronate reduced steroid-induced bone resorption.

Trust comment: Moderate-quality clinical study with randomized allocation in reduced BMD subgroup but modest sample size and biomarker-focused outcomes.

Study Details

PMID:22728519
Participants:73
Impact:suppressed (resorption markers decreased when alendronate given)
Trust score:3/5

bone mineral density (BMD) T-score

1 evidences

Adding calcitriol to esomeprazole did not improve bone mineral density; only minor changes in calcium and bone markers were observed.

Trust comment: Large randomized study but treatment exposure was very short (~10 days), limiting ability to detect BMD changes.

Study Details

PMID:25046547
Participants:386
Impact:no meaningful change with calcitriol versus control
Trust score:3/5

carboxy-terminal collagen crosslinks (CTX)

1 evidences

Adding calcitriol to esomeprazole did not improve bone mineral density; only minor changes in calcium and bone markers were observed.

Trust comment: Large randomized study but treatment exposure was very short (~10 days), limiting ability to detect BMD changes.

Study Details

PMID:25046547
Participants:386
Impact:no clinically meaningful between-group difference (reported 366.6 vs 373.1 pg/mL; p=0.036)
Trust score:3/5

C1M (type I collagen degradation)

2 evidences

Biomarker sub-study of an RCT in RA showing tocilizumab reduces collagen-degradation biomarkers and CRP more than methotrexate by week 8.

Trust comment: Large, randomized phase‑3 trial sub-study with validated assays and appropriate statistics, but limited to short (8‑week) biomarker follow‑up.

Study Details

PMID:33413588
Participants:387
Impact:↓ significant with tocilizumab vs placebo; 23% greater reduction vs methotrexate
Trust score:4/5

Clustering of blood ECM (including collagen) biomarkers identified three patient endotypes with different disease activity and differential response to adalimumab.

Trust comment: Exploratory post-hoc analysis pooling three clinical cohorts (moderate sample) with appropriate biomarker assays but requires external validation.

Study Details

PMID:38199849
Participants:135
Impact:major driver of inflammation-related biomarker dimension (high in Endotype1)
Trust score:3/5

PRO-C2 (type II collagen formation)

1 evidences

Clustering of blood ECM (including collagen) biomarkers identified three patient endotypes with different disease activity and differential response to adalimumab.

Trust comment: Exploratory post-hoc analysis pooling three clinical cohorts (moderate sample) with appropriate biomarker assays but requires external validation.

Study Details

PMID:38199849
Participants:135
Impact:major driver of collagen turnover/cartilage dimension (high in Endotype3)
Trust score:3/5

treatment response by endotype (ASDAS/BASDAI)

1 evidences

Clustering of blood ECM (including collagen) biomarkers identified three patient endotypes with different disease activity and differential response to adalimumab.

Trust comment: Exploratory post-hoc analysis pooling three clinical cohorts (moderate sample) with appropriate biomarker assays but requires external validation.

Study Details

PMID:38199849
Participants:135
Impact:Endotype1 had higher ASDAS major improvement; Endotype3 had higher BASDAI50 response versus Endotype2
Trust score:3/5

clinical symptoms (VISA-p, VAS)

1 evidences

All treatments improved symptoms short-term; heavy slow resistance training gave better long-term outcomes and increased collagen network turnover.

Trust comment: Randomized single-blind trial with small sample (n=39) and meaningful clinical and biomarker outcomes, limiting generalizability.

Study Details

PMID:19793213
Participants:39
Impact:improved in all groups at 12 weeks; maintained in ECC and HSR, deteriorated in corticosteroid group by 6 months
Trust score:3/5

tendon swelling and vascularization

1 evidences

All treatments improved symptoms short-term; heavy slow resistance training gave better long-term outcomes and increased collagen network turnover.

Trust comment: Randomized single-blind trial with small sample (n=39) and meaningful clinical and biomarker outcomes, limiting generalizability.

Study Details

PMID:19793213
Participants:39
Impact:decreased in CORT and HSR at 12 weeks (swelling ≈ -12% to -13%; vascularization large reductions)
Trust score:3/5

collagen network turnover

1 evidences

All treatments improved symptoms short-term; heavy slow resistance training gave better long-term outcomes and increased collagen network turnover.

Trust comment: Randomized single-blind trial with small sample (n=39) and meaningful clinical and biomarker outcomes, limiting generalizability.

Study Details

PMID:19793213
Participants:39
Impact:increased with heavy slow resistance training (HSR)
Trust score:3/5

C1M (type I collagen turnover)

1 evidences

Inflammatory hand OA patients showed biomarker variation; prednisolone did not change most collagen-related biomarkers over 6 weeks.

Trust comment: Post-hoc biomarker analysis of an RCT with moderate sample size; assays well described but limited by short treatment duration and exploratory nature.

Study Details

PMID:35946535
Participants:78
Impact:higher in patients with erosive disease (geometric mean ratio 1.24) and overall not reduced by prednisolone
Trust score:3/5

VICM (citrullinated vimentin fragment)

1 evidences

Inflammatory hand OA patients showed biomarker variation; prednisolone did not change most collagen-related biomarkers over 6 weeks.

Trust comment: Post-hoc biomarker analysis of an RCT with moderate sample size; assays well described but limited by short treatment duration and exploratory nature.

Study Details

PMID:35946535
Participants:78
Impact:slight increase after prednisolone (GMR ~1.22 at week 6)
Trust score:3/5

mid-ridge height change

1 evidences

Prospective randomized pilot study testing alveolar ridge preservation with DBBM (particulate) or DBBM-C (DBBM stabilized in 10% porcine type I collagen) versus unassisted healing; ARP maintained mid-ridge height and reduced sinus pneumatization and the need for lateral sinus augmentation.

Trust comment: Prospective randomized pilot RCT with objective 3D CT endpoints and blinded measurements but small sample and some excluded scans limiting power.

Study Details

PMID:39165113
Participants:25
Impact:Control −2.7±0.9 mm (−39.7%); Test1 (DBBM) +0.9±3.7 mm (+15.3%); Test2 (DBBM‑C) +1.0±2.8 mm (+18.5%)
Trust score:4/5

sinus volume change

1 evidences

Prospective randomized pilot study testing alveolar ridge preservation with DBBM (particulate) or DBBM-C (DBBM stabilized in 10% porcine type I collagen) versus unassisted healing; ARP maintained mid-ridge height and reduced sinus pneumatization and the need for lateral sinus augmentation.

Trust comment: Prospective randomized pilot RCT with objective 3D CT endpoints and blinded measurements but small sample and some excluded scans limiting power.

Study Details

PMID:39165113
Participants:25
Impact:Control +0.7±0.7 cm³ (+3.9%); Test1 −0.7±0.8 cm³ (−3.7%); Test2 +0.1±0.3 cm³ (+0.8%)
Trust score:4/5

need for lateral window sinus augmentation

1 evidences

Prospective randomized pilot study testing alveolar ridge preservation with DBBM (particulate) or DBBM-C (DBBM stabilized in 10% porcine type I collagen) versus unassisted healing; ARP maintained mid-ridge height and reduced sinus pneumatization and the need for lateral sinus augmentation.

Trust comment: Prospective randomized pilot RCT with objective 3D CT endpoints and blinded measurements but small sample and some excluded scans limiting power.

Study Details

PMID:39165113
Participants:25
Impact:Control 8/9 (89%); Test1 3/7 (43%); Test2 4/10 (40%)
Trust score:4/5

photodamage improvement (blinded evaluator)

1 evidences

Double-blind randomized trial of tretinoin 0.05% lotion vs vehicle (vehicle contained soluble collagen among other hydrators) for chest photorejuvenation; both active and vehicle groups improved similarly by 180 days with mild, transient erythema higher in active at day 90.

Trust comment: Randomized double-blind vehicle-controlled human trial but small sample and vehicle contained collagen, complicating attribution of effects to tretinoin vs vehicle.

Study Details

PMID:35674757
Participants:29
Impact:+30–40% improvement at day 180 in both active and vehicle groups
Trust score:4/5

facial bone thickness (FBT)

1 evidences

Randomized clinical trial comparing collagen plug, demineralized bone matrix (Grafton) and particulate autogenous+DBBM (MinerOss X) with vestibular socket therapy in immediate implants; all groups had good esthetic outcomes and increased facial bone thickness, with no significant differences between groups.

Trust comment: Randomized controlled clinical trial with clear radiographic outcomes but small sample (n=24) limiting between-group comparisons.

Study Details

PMID:37658342
Participants:24
Impact:All groups: significant increase vs baseline (Collagen plug 0.21→1.03 mm; Grafton 0.27→1.06 mm; MinerOss X 0.35→1.19–1.44 mm); no significant between-group differences at 6 or 12 months
Trust score:3/5

soft tissue vertical height

1 evidences

Randomized clinical trial comparing collagen plug, demineralized bone matrix (Grafton) and particulate autogenous+DBBM (MinerOss X) with vestibular socket therapy in immediate implants; all groups had good esthetic outcomes and increased facial bone thickness, with no significant differences between groups.

Trust comment: Randomized controlled clinical trial with clear radiographic outcomes but small sample (n=24) limiting between-group comparisons.

Study Details

PMID:37658342
Participants:24
Impact:Maintained across groups (~0.55 mm change) with no significant differences between groups
Trust score:3/5

Soft tissue percentage

1 evidences

Randomized clinical trial comparing flapped vs flapless socket grafting with porcine bone and collagen membrane found similar histological outcomes after 3 months.

Trust comment: Randomized clinical trial with quantitative histomorphometry (34 patients); reasonable quality for histologic endpoints.

Study Details

PMID:24580835
Participants:34
Impact:~59.3% (no difference between groups)
Trust score:4/5

Oswestry Disability Index (ODI)

1 evidences

Randomized double-blind trial of a multi-nutrient supplement (including collagen type II) vs placebo for lumbar osteochondrosis; no differences in patient-reported outcomes, but supplement group showed significant increases in 3D-measured intervertebral disc (IVD) volumes.

Trust comment: Randomized double-blind placebo-controlled trial but under-enrolled vs planned sample and short duration; MRI volumetric result is significant but clinical PROMs were not.

Study Details

PMID:39203831
Participants:45
Impact:no significant between-group difference
Trust score:4/5

vertical bone fill (VBF)

1 evidences

A mineralized cancellous allograft (with or without a collagen membrane) improved vertical bone fill versus open flap debridement in mandibular Class II furcation defects.

Trust comment: Randomized clinical design with 27 completers and objective measurements; small sample limits precision.

Study Details

PMID:16512756
Participants:27
Impact:OFD -1.6±2.1 mm; MBA 1.9±1.4 mm; GTR+MBA 0.7±0.9 mm (MBA and GTR+MBA > OFD, P<0.05)
Trust score:3/5

horizontal bone fill (HBF)

1 evidences

A mineralized cancellous allograft (with or without a collagen membrane) improved vertical bone fill versus open flap debridement in mandibular Class II furcation defects.

Trust comment: Randomized clinical design with 27 completers and objective measurements; small sample limits precision.

Study Details

PMID:16512756
Participants:27
Impact:OFD 0.2±1.7 mm; MBA 1.1±0.9 mm; GTR+MBA 1.1±0.9 mm (no significant intergroup differences)
Trust score:3/5

buccal volumetric variation (BVv) at 1 month

1 evidences

At 1 month collagen matrix sealing showed greater early buccal volumetric loss than customized abutments, but at 1 year there were no significant differences between groups.

Trust comment: Prospective randomized clinical trial with clear measurements but small sample (28) limits generalizability.

Study Details

PMID:34423560
Participants:28
Impact:CM -9.75±6.65% vs CA -4.76±5.29% (p=0.043)
Trust score:3/5

buccal volumetric variation (BVv) at 12 months

1 evidences

At 1 month collagen matrix sealing showed greater early buccal volumetric loss than customized abutments, but at 1 year there were no significant differences between groups.

Trust comment: Prospective randomized clinical trial with clear measurements but small sample (28) limits generalizability.

Study Details

PMID:34423560
Participants:28
Impact:no significant difference between CM and CA at 1 year
Trust score:3/5

midfacial mucosa and papillae alteration

1 evidences

At 1 month collagen matrix sealing showed greater early buccal volumetric loss than customized abutments, but at 1 year there were no significant differences between groups.

Trust comment: Prospective randomized clinical trial with clear measurements but small sample (28) limits generalizability.

Study Details

PMID:34423560
Participants:28
Impact:no significant differences after 1 year
Trust score:3/5

IL-6 (inflammatory marker)

1 evidences

2 months of simvastatin (40 mg/day) in hypercholesterolemic patients reduced multiple inflammatory markers and platelet aggregation and increased platelet sensitivity to aspirin.

Trust comment: Randomized controlled trial in humans with clear biomarker and functional platelet outcomes but modest sample size and short duration limit generalizability.

Study Details

PMID:30402489
Participants:45
Impact:-27%
Trust score:4/5

Platelet aggregation to ADP (maximal aggregation)

1 evidences

2 months of simvastatin (40 mg/day) in hypercholesterolemic patients reduced multiple inflammatory markers and platelet aggregation and increased platelet sensitivity to aspirin.

Trust comment: Randomized controlled trial in humans with clear biomarker and functional platelet outcomes but modest sample size and short duration limit generalizability.

Study Details

PMID:30402489
Participants:45
Impact:-22%
Trust score:4/5

Platelet sensitivity to aspirin (L-ASA IC-50 to AA)

1 evidences

2 months of simvastatin (40 mg/day) in hypercholesterolemic patients reduced multiple inflammatory markers and platelet aggregation and increased platelet sensitivity to aspirin.

Trust comment: Randomized controlled trial in humans with clear biomarker and functional platelet outcomes but modest sample size and short duration limit generalizability.

Study Details

PMID:30402489
Participants:45
Impact:-65%
Trust score:4/5

Mid-facial marginal mucosal margin change

1 evidences

In this RCT of early implant placement, use of a collagen-containing ARP material produced similar one-year esthetic, clinical and patient-reported outcomes compared with ARP with palatal graft or no ARP.

Trust comment: Multicenter randomized controlled trial (n=75) with blinded measurement procedures and 1-year follow-up; well powered for primary endpoint.

Study Details

PMID:34129708
Participants:75
Impact:-0.02 mm (median, CM group)
Trust score:5/5

Peri-implant esthetic score (PES)

1 evidences

In this RCT of early implant placement, use of a collagen-containing ARP material produced similar one-year esthetic, clinical and patient-reported outcomes compared with ARP with palatal graft or no ARP.

Trust comment: Multicenter randomized controlled trial (n=75) with blinded measurement procedures and 1-year follow-up; well powered for primary endpoint.

Study Details

PMID:34129708
Participants:75
Impact:+0.7 points (6.3 → 7.0 mean, CM group baseline→FU-1)
Trust score:5/5

Implant survival at 1 year

2 evidences

Randomized clinical study of two graft materials with the same collagen barrier showed 100% implant survival and similar clinical and radiographic outcomes at 1-year post-loading.

Trust comment: Small randomized clinical study; collagen barrier was used in both arms so it does not isolate collagen effect.

Study Details

PMID:22672611
Participants:27
Impact:100% survival in both groups
Trust score:3/5

In this RCT of early implant placement, use of a collagen-containing ARP material produced similar one-year esthetic, clinical and patient-reported outcomes compared with ARP with palatal graft or no ARP.

Trust comment: Multicenter randomized controlled trial (n=75) with blinded measurement procedures and 1-year follow-up; well powered for primary endpoint.

Study Details

PMID:34129708
Participants:75
Impact:100% (CM group)
Trust score:5/5

connective tissue/other percentage

1 evidences

Compared two xenograft ridge-preservation protocols in humans; the protocol using a cross-linked bovine collagen sponge produced more vital bone than the other, while clinical dimensional changes were similar.

Trust comment: Randomized controlled trial with histologic endpoints in 44 patients; moderate sample and clear results support moderate-high trust.

Study Details

PMID:22680300
Participants:44
Impact:no significant difference (~53%; P = 0.763)
Trust score:4/5

incidence of alveolar air leaks

1 evidences

Randomized trial comparing electrocautery plus a collagen patch sealant versus stapler for lobectomy; the collagen-patch group had fewer and shorter air leaks and lower costs.

Trust comment: Randomized controlled pilot (40 patients) with significant clinical endpoints, but small sample size limits generalizability.

Study Details

PMID:18692646
Participants:40
Impact:reduced from 95% to 50% (−45 percentage points)
Trust score:4/5

duration of air leaks

1 evidences

Randomized trial comparing electrocautery plus a collagen patch sealant versus stapler for lobectomy; the collagen-patch group had fewer and shorter air leaks and lower costs.

Trust comment: Randomized controlled pilot (40 patients) with significant clinical endpoints, but small sample size limits generalizability.

Study Details

PMID:18692646
Participants:40
Impact:-2.8 days (1.7 vs 4.5 days)
Trust score:4/5

procedure costs

1 evidences

Randomized trial comparing electrocautery plus a collagen patch sealant versus stapler for lobectomy; the collagen-patch group had fewer and shorter air leaks and lower costs.

Trust comment: Randomized controlled pilot (40 patients) with significant clinical endpoints, but small sample size limits generalizability.

Study Details

PMID:18692646
Participants:40
Impact:-205.5 euros (425 vs 630.5 euros)
Trust score:4/5

mid-buccal mucosal level change

1 evidences

RCT comparing no graft, connective tissue graft, and xenogeneic collagen matrix at implant placement; no significant differences in esthetic outcomes or peri-implant health at 12 months.

Trust comment: Randomized trial with 60 patients and 12-month follow-up; well-designed but found no effect of collagen matrix on primary clinical/esthetic outcomes.

Study Details

PMID:29756213
Participants:60
Impact:no significant difference (XCM −0.17 mm vs NG −0.48 mm; P = 0.56)
Trust score:4/5

esthetic outcome / peri-implant health

1 evidences

RCT comparing no graft, connective tissue graft, and xenogeneic collagen matrix at implant placement; no significant differences in esthetic outcomes or peri-implant health at 12 months.

Trust comment: Randomized trial with 60 patients and 12-month follow-up; well-designed but found no effect of collagen matrix on primary clinical/esthetic outcomes.

Study Details

PMID:29756213
Participants:60
Impact:no significant intergroup differences
Trust score:4/5

seroma occurrence

1 evidences

Randomized blinded trial of a collagen sponge coated with human coagulation factors after axillary lymphadenectomy; use was associated with a lower incidence of postoperative seroma.

Trust comment: Prospective randomized blinded study in 91 procedures with multivariate analysis showing reduced seroma; moderate trustworthiness.

Study Details

PMID:27338717
Participants:91
Impact:reduced; use associated with nonoccurrence (multivariate OR 3.365 for nonoccurrence; P = 0.046)
Trust score:4/5

IVD volume change (3D MRI)

1 evidences

Randomized double-blind trial of a multi-nutrient supplement (including collagen type II) vs placebo for lumbar osteochondrosis; no differences in patient-reported outcomes, but supplement group showed significant increases in 3D-measured intervertebral disc (IVD) volumes.

Trust comment: Randomized double-blind placebo-controlled trial but under-enrolled vs planned sample and short duration; MRI volumetric result is significant but clinical PROMs were not.

Study Details

PMID:39203831
Participants:45
Impact:supplement +740.3 ± 796.1 mm³ vs placebo −417.2 ± 875.0 mm³ (between-group difference significant; P < 0.001)
Trust score:4/5

VAS back pain

1 evidences

Randomized double-blind trial of a multi-nutrient supplement (including collagen type II) vs placebo for lumbar osteochondrosis; no differences in patient-reported outcomes, but supplement group showed significant increases in 3D-measured intervertebral disc (IVD) volumes.

Trust comment: Randomized double-blind placebo-controlled trial but under-enrolled vs planned sample and short duration; MRI volumetric result is significant but clinical PROMs were not.

Study Details

PMID:39203831
Participants:45
Impact:no significant between-group difference (placebo showed within-group improvement)
Trust score:4/5

composite ≥2-level improvement (CR-PCSS & PR-PCSS)

1 evidences

In this randomized double-blind placebo-controlled trial, injections of collagenase improved clinician- and patient-rated cellulite severity and patient satisfaction versus placebo and were generally well tolerated.

Trust comment: Large (n=375), randomized, double-blind, placebo-controlled Phase 2b trial with validated clinician and patient endpoints.

Study Details

PMID:30829779
Participants:375
Impact:10.6% responders (CCH) vs 1.6% (placebo)
Trust score:5/5

composite ≥1-level improvement (CR-PCSS & PR-PCSS)

1 evidences

In this randomized double-blind placebo-controlled trial, injections of collagenase improved clinician- and patient-rated cellulite severity and patient satisfaction versus placebo and were generally well tolerated.

Trust comment: Large (n=375), randomized, double-blind, placebo-controlled Phase 2b trial with validated clinician and patient endpoints.

Study Details

PMID:30829779
Participants:375
Impact:44.6% (CCH) vs 17.9% (placebo)
Trust score:5/5

patient satisfaction (satisfied/very satisfied)

1 evidences

In this randomized double-blind placebo-controlled trial, injections of collagenase improved clinician- and patient-rated cellulite severity and patient satisfaction versus placebo and were generally well tolerated.

Trust comment: Large (n=375), randomized, double-blind, placebo-controlled Phase 2b trial with validated clinician and patient endpoints.

Study Details

PMID:30829779
Participants:375
Impact:62.9% (CCH) vs 35.9% (placebo)
Trust score:5/5

scar severity score improvement (group 1: PCI + TCA)

1 evidences

In 39 patients with atrophic acne scars, combined alternating sessions of fractional laser and percutaneous collagen induction + TCA produced greater mean scar‑severity improvement than either treatment alone.

Trust comment: Randomized controlled trial in humans but small sample (n=39); results show statistically significant benefit for the combined approach.

Study Details

PMID:22640000
Participants:39
Impact:mean 59.79% improvement (95% CI 47.38–72.21)
Trust score:3/5

scar severity score improvement (group 2: 1540 nm laser)

1 evidences

In 39 patients with atrophic acne scars, combined alternating sessions of fractional laser and percutaneous collagen induction + TCA produced greater mean scar‑severity improvement than either treatment alone.

Trust comment: Randomized controlled trial in humans but small sample (n=39); results show statistically significant benefit for the combined approach.

Study Details

PMID:22640000
Participants:39
Impact:mean 61.83% improvement (95% CI 54.09–69.56)
Trust score:3/5

scar severity score improvement (group 3: combined alternating)

1 evidences

In 39 patients with atrophic acne scars, combined alternating sessions of fractional laser and percutaneous collagen induction + TCA produced greater mean scar‑severity improvement than either treatment alone.

Trust comment: Randomized controlled trial in humans but small sample (n=39); results show statistically significant benefit for the combined approach.

Study Details

PMID:22640000
Participants:39
Impact:mean 78.27% improvement (95% CI 74.39–82.15); combined superior (p=0.004)
Trust score:3/5

Bone volume (BV)

1 evidences

Randomized trial of sandwich bone augmentation with a collagen (bovine pericardium) barrier membrane showed preserved bone volume but delayed outer-layer maturation and less mineralization versus no membrane.

Trust comment: Randomized clinical trial but small sample and only a subset of biopsies were analyzable, limiting precision; directly evaluates a collagen membrane biomaterial.

Study Details

PMID:25220909
Participants:26
Impact:Maintained in collagen membrane group vs compromised in control group
Trust score:3/5

Bone volume fraction (BV/TV)

1 evidences

Both techniques (non-resorbable membrane vs titanium mesh + collagen membrane) produced ~30% newly formed bone by micro-CT with no significant differences between groups.

Trust comment: Randomized human study (n=40) with objective micro-CT endpoints; moderate quality but limited sample for subgroup inference about collagen membrane specifics.

Study Details

PMID:34006069
Participants:40
Impact:~28.8% (group A) vs ~30.0% (group B); no significant difference
Trust score:3/5

Skin wrinkles

1 evidences

Daily C. rabens extract (180 mg) for 4 weeks improved several skin-aging measures including reduced wrinkles and increased collagen-associated parameters compared with placebo.

Trust comment: Randomized, double-blind, placebo-controlled human trial with complete follow-up, but small sample and short (4-week) duration limit generalizability.

Study Details

PMID:35807836
Participants:40
Impact:Mean change −3.8 (treatment) vs +0.1 (placebo) at 4 weeks
Trust score:4/5

Skin hydration / brightness

1 evidences

Daily C. rabens extract (180 mg) for 4 weeks improved several skin-aging measures including reduced wrinkles and increased collagen-associated parameters compared with placebo.

Trust comment: Randomized, double-blind, placebo-controlled human trial with complete follow-up, but small sample and short (4-week) duration limit generalizability.

Study Details

PMID:35807836
Participants:40
Impact:Significant improvement in skin hydration and brightness in treatment group vs baseline (distinguishable from placebo for brightness)
Trust score:4/5

Serum N-terminal telopeptides of type-1 collagen (NTx)

1 evidences

Alendronate prevented periprosthetic BMD loss around femoral implants and reduced serum N-terminal telopeptides of type-1 collagen; alfacalcidol preserved lumbar spine BMD but did not prevent periprosthetic loss.

Trust comment: Human clinical study with clear BMD and collagen turnover markers; relevant to collagen metabolism but not an intervention using collagen itself.

Study Details

PMID:21776573
Participants:60
Impact:Lower in alendronate group vs no-medication throughout the study (significant)
Trust score:3/5

re-epithelialized area

1 evidences

Treatment with acellular porcine dermis (PD) or polynucleotides-added hyaluronic acid (PAHA) healed chronic ulcers faster and increased markers of tissue repair compared with polyurethane foam.

Trust comment: Small randomized single-blind clinical trial (n=30) with objective histology and imaging but limited sample size and short follow-up.

Study Details

PMID:32710584
Participants:30
Impact:increased (PD and PAHA vs polyurethane foam; P<0.05 and P<0.01 respectively)
Trust score:3/5

collagen type I deposition

1 evidences

Treatment with acellular porcine dermis (PD) or polynucleotides-added hyaluronic acid (PAHA) healed chronic ulcers faster and increased markers of tissue repair compared with polyurethane foam.

Trust comment: Small randomized single-blind clinical trial (n=30) with objective histology and imaging but limited sample size and short follow-up.

Study Details

PMID:32710584
Participants:30
Impact:increased (PD and PAHA vs polyurethane foam; P<0.05)
Trust score:3/5

neo-angiogenesis (CD34+)

1 evidences

Treatment with acellular porcine dermis (PD) or polynucleotides-added hyaluronic acid (PAHA) healed chronic ulcers faster and increased markers of tissue repair compared with polyurethane foam.

Trust comment: Small randomized single-blind clinical trial (n=30) with objective histology and imaging but limited sample size and short follow-up.

Study Details

PMID:32710584
Participants:30
Impact:increased (PD and PAHA vs polyurethane foam; P<0.01)
Trust score:3/5

cross-sectional ridge area change

1 evidences

Grafting fresh extraction sockets with Bio-Oss Collagen largely preserved cross-sectional ridge area compared with no grafting over 4 months.

Trust comment: Randomized clinical trial with objective CBCT measurements but relatively small sample (n=28); endpoints clinically relevant.

Study Details

PMID:24621203
Participants:28
Impact:test (Bio-Oss Collagen) −3% vs control −25% after 4 months
Trust score:4/5

buccal and palatal bone height

1 evidences

Grafting fresh extraction sockets with Bio-Oss Collagen largely preserved cross-sectional ridge area compared with no grafting over 4 months.

Trust comment: Randomized clinical trial with objective CBCT measurements but relatively small sample (n=28); endpoints clinically relevant.

Study Details

PMID:24621203
Participants:28
Impact:marked height reduction observed in both groups after 4 months (grafting did not fully prevent height loss)
Trust score:4/5

hard tissue component preservation

1 evidences

Grafting fresh extraction sockets with Bio-Oss Collagen largely preserved cross-sectional ridge area compared with no grafting over 4 months.

Trust comment: Randomized clinical trial with objective CBCT measurements but relatively small sample (n=28); endpoints clinically relevant.

Study Details

PMID:24621203
Participants:28
Impact:grafting markedly counteracted reduction in hard tissue component (reflected in smaller area loss)
Trust score:4/5

skin elasticity (viscoelasticity)

1 evidences

Sixty women randomized to topical peptides, oral hydrolyzed collagen, or placebo: oral collagen improved skin elasticity, increased dermis echogenicity, and reduced pores after 90 days.

Trust comment: Human randomized study on hydrolyzed collagen with objective biophysical measures but modest sample size and limited detail on blinding.

Study Details

PMID:30834689
Participants:60
Impact:improved (oral supplementation; observed by 90 days)
Trust score:3/5

dermis echogenicity (skin density)

1 evidences

Sixty women randomized to topical peptides, oral hydrolyzed collagen, or placebo: oral collagen improved skin elasticity, increased dermis echogenicity, and reduced pores after 90 days.

Trust comment: Human randomized study on hydrolyzed collagen with objective biophysical measures but modest sample size and limited detail on blinding.

Study Details

PMID:30834689
Participants:60
Impact:increased (more pronounced with oral hydrolyzed collagen at 90 days)
Trust score:3/5

skin pores

1 evidences

Sixty women randomized to topical peptides, oral hydrolyzed collagen, or placebo: oral collagen improved skin elasticity, increased dermis echogenicity, and reduced pores after 90 days.

Trust comment: Human randomized study on hydrolyzed collagen with objective biophysical measures but modest sample size and limited detail on blinding.

Study Details

PMID:30834689
Participants:60
Impact:reduced (oral supplementation at 90 days)
Trust score:3/5

Pro-C3 (type III collagen formation marker)

1 evidences

Analysis of serum collagen-related ECM markers (eg, Pro-C3) in PSC patients showing correlations with fibrosis stage and prognosis.

Trust comment: Large (n=234) prospective phase 2b trial dataset with central histology and rigorous analyses, providing robust correlative evidence.

Study Details

PMID:38967589
Participants:234
Impact:moderate correlation with Ishak fibrosis stage (ρ = 0.48) and AUROC ~0.73 for advanced fibrosis
Trust score:5/5

ELF score

1 evidences

Analysis of serum collagen-related ECM markers (eg, Pro-C3) in PSC patients showing correlations with fibrosis stage and prognosis.

Trust comment: Large (n=234) prospective phase 2b trial dataset with central histology and rigorous analyses, providing robust correlative evidence.

Study Details

PMID:38967589
Participants:234
Impact:moderate discrimination/prognostic ability (AUROC ~0.71) for clinical events and cirrhosis
Trust score:5/5

fibrosis progression (biopsy)

1 evidences

Analysis of serum collagen-related ECM markers (eg, Pro-C3) in PSC patients showing correlations with fibrosis stage and prognosis.

Trust comment: Large (n=234) prospective phase 2b trial dataset with central histology and rigorous analyses, providing robust correlative evidence.

Study Details

PMID:38967589
Participants:234
Impact:higher baseline and increases in Pro-C3/ELF associated with fibrosis progression and progression to cirrhosis
Trust score:5/5

sternal wound infection (90 days)

1 evidences

Large multicenter randomized trial testing gentamicin-collagen sponge versus no sponge to prevent sternal wound infection in high-risk cardiac surgery patients.

Trust comment: Large, multicenter randomized controlled trial (n=1502) with blinded adjudication, high methodological quality.

Study Details

PMID:20716738
Participants:1502
Impact:no significant difference: 8.4% (sponge) vs 8.7% (control), P = .83
Trust score:5/5

superficial sternal wound infection

1 evidences

Large multicenter randomized trial testing gentamicin-collagen sponge versus no sponge to prevent sternal wound infection in high-risk cardiac surgery patients.

Trust comment: Large, multicenter randomized controlled trial (n=1502) with blinded adjudication, high methodological quality.

Study Details

PMID:20716738
Participants:1502
Impact:no significant difference: 6.5% vs 6.1%, P = .77
Trust score:5/5

deep sternal wound infection

1 evidences

Large multicenter randomized trial testing gentamicin-collagen sponge versus no sponge to prevent sternal wound infection in high-risk cardiac surgery patients.

Trust comment: Large, multicenter randomized controlled trial (n=1502) with blinded adjudication, high methodological quality.

Study Details

PMID:20716738
Participants:1502
Impact:no significant difference: 1.9% vs 2.5%, P = .37
Trust score:5/5

Smile Esthetic Index (SEI) change

1 evidences

Randomized human trial comparing coronally advanced flap (CAF) with or without a xenogeneic collagen matrix (CMX): adding CMX produced slightly greater objective SEI change but differences were not statistically significant at 1 year.

Trust comment: Randomized human trial (n=24) using validated objective and subjective esthetic measures; small sample and primary outcome borderline non-significant.

Study Details

PMID:32772215
Participants:24
Impact:Test (CAF+CMX) +0.7±0.5 vs Control (CAF) +0.3±0.5; between-group difference +0.4 (95% CI −0.0 to 0.8), P=0.0697
Trust score:4/5

Esthetics VAS (patient-reported) at 1 year

1 evidences

Randomized human trial comparing coronally advanced flap (CAF) with or without a xenogeneic collagen matrix (CMX): adding CMX produced slightly greater objective SEI change but differences were not statistically significant at 1 year.

Trust comment: Randomized human trial (n=24) using validated objective and subjective esthetic measures; small sample and primary outcome borderline non-significant.

Study Details

PMID:32772215
Participants:24
Impact:Test mean 9.3±1.0 vs Control 8.8±2.0; difference 0.4, P=0.5094
Trust score:4/5

Horizontal ridge shrinkage (mm)

1 evidences

Randomized human study: grafting sockets with collagenated bovine-derived bone plus collagen membrane markedly reduced horizontal shrinkage and volume loss versus spontaneous healing at 12 months.

Trust comment: Randomized controlled human study (n=30) with objective CBCT measurements and large, significant differences favouring collagenated graft + membrane.

Study Details

PMID:29148597
Participants:30
Impact:Control 4.92±2.45 mm vs Grafted 2.60±1.24 mm (less shrinkage with graft)
Trust score:4/5

Buccal wall rebuilding (mm)

1 evidences

Randomized human study: grafting sockets with collagenated bovine-derived bone plus collagen membrane markedly reduced horizontal shrinkage and volume loss versus spontaneous healing at 12 months.

Trust comment: Randomized controlled human study (n=30) with objective CBCT measurements and large, significant differences favouring collagenated graft + membrane.

Study Details

PMID:29148597
Participants:30
Impact:Grafted 2.50±2.12 mm vs Control 0.51±1.02 mm (greater rebuilding with graft)
Trust score:4/5

Volume loss (%)

2 evidences

Using a collagenated bovine bone mineral and a resorbable collagen membrane for ridge preservation reduced post-extraction ridge shrinkage and volumetric loss compared with spontaneous healing.

Trust comment: Randomized controlled trial directly using collagen-containing materials but small sample (n=26) which limits generalizability despite clear imaging and histologic endpoints.

Study Details

PMID:33316099
Participants:26
Impact:RP −26.53% vs SH −50.34% (p<0.05)
Trust score:3/5

Randomized human study: grafting sockets with collagenated bovine-derived bone plus collagen membrane markedly reduced horizontal shrinkage and volume loss versus spontaneous healing at 12 months.

Trust comment: Randomized controlled human study (n=30) with objective CBCT measurements and large, significant differences favouring collagenated graft + membrane.

Study Details

PMID:29148597
Participants:30
Impact:Grafted 9.14% vs Non-grafted 35.16% (p<0.0001)
Trust score:4/5

collagen IV expression

1 evidences

A topical eye cream (56 days, 33 women) increased collagen IV and elastin markers ex vivo and reduced periorbital wrinkle depth and improved hydration instrumentally and clinically.

Trust comment: Human clinical measurements with objective endpoints (n=33) but single‑arm topical study with industry funding and author employment by funder, raising bias risk.

Study Details

PMID:39119663
Participants:33
Impact:+14% vs untreated; +9% vs placebo (immunohistochemistry)
Trust score:3/5

elastin fibre length

1 evidences

A topical eye cream (56 days, 33 women) increased collagen IV and elastin markers ex vivo and reduced periorbital wrinkle depth and improved hydration instrumentally and clinically.

Trust comment: Human clinical measurements with objective endpoints (n=33) but single‑arm topical study with industry funding and author employment by funder, raising bias risk.

Study Details

PMID:39119663
Participants:33
Impact:+43% vs untreated; +42% vs placebo (immunohistochemistry)
Trust score:3/5

crow's feet wrinkle depth (Sv)

1 evidences

A topical eye cream (56 days, 33 women) increased collagen IV and elastin markers ex vivo and reduced periorbital wrinkle depth and improved hydration instrumentally and clinically.

Trust comment: Human clinical measurements with objective endpoints (n=33) but single‑arm topical study with industry funding and author employment by funder, raising bias risk.

Study Details

PMID:39119663
Participants:33
Impact:−12% (249.2→219.1 μm at 56 days)
Trust score:3/5

Collagen gene expression (COL1, COL3, COL5)

1 evidences

Topical DHEA increased expression of multiple collagen genes and altered keratinocyte-related genes in postmenopausal women's skin.

Trust comment: Randomized, double-blind, placebo-controlled phase II trial with clear genomic endpoints but no direct clinical collagen endpoints.

Study Details

PMID:19013239
Participants:60
Impact:+ (dose-dependent increase, p<0.05)
Trust score:4/5

SPARC expression (collagen fibril deposition regulator)

1 evidences

Topical DHEA increased expression of multiple collagen genes and altered keratinocyte-related genes in postmenopausal women's skin.

Trust comment: Randomized, double-blind, placebo-controlled phase II trial with clear genomic endpoints but no direct clinical collagen endpoints.

Study Details

PMID:19013239
Participants:60
Impact:Modulated (dose-dependent, p<0.05)
Trust score:4/5

Keratinocyte terminal differentiation gene expression

1 evidences

Topical DHEA increased expression of multiple collagen genes and altered keratinocyte-related genes in postmenopausal women's skin.

Trust comment: Randomized, double-blind, placebo-controlled phase II trial with clear genomic endpoints but no direct clinical collagen endpoints.

Study Details

PMID:19013239
Participants:60
Impact:Decreased (p<0.05)
Trust score:4/5

PD reduction and CAL gain vs access flap

1 evidences

Use of a collagen membrane with bovine bone graft improved periodontal pocket depth and attachment over 12 months compared with flap procedure alone.

Trust comment: Prospective randomized controlled clinical trial with 12-month follow-up; moderate sample size and clinically relevant endpoints.

Study Details

PMID:15367197
Participants:34
Impact:Greater than AFP (p<0.05)
Trust score:4/5

Airway vessel number and percent vascularity

1 evidences

Six months of inhaled beclomethasone reduced airway mucosal vascularity and was associated with changes in subepithelial collagen III thickness in asthmatic patients.

Trust comment: Double-blind randomized trial with histologic endpoints in humans, but small sample size limits generalizability.

Study Details

PMID:11422131
Participants:28
Impact:Decreased with inhaled BDP vs placebo (P<0.05)
Trust score:4/5

Collagen III thickness correlation

1 evidences

Six months of inhaled beclomethasone reduced airway mucosal vascularity and was associated with changes in subepithelial collagen III thickness in asthmatic patients.

Trust comment: Double-blind randomized trial with histologic endpoints in humans, but small sample size limits generalizability.

Study Details

PMID:11422131
Participants:28
Impact:Change in vascularity correlated with change in collagen III thickness (rs = 0.90, P<0.001)
Trust score:4/5

grafted bone volume

1 evidences

Pilot RCT comparing two collagen barrier membranes for guided bone regeneration: both membranes showed graft volume loss and no significant differences between them.

Trust comment: Randomized controlled human trial with objective CBCT measures and high inter-observer reliability but small pilot sample (n=36).

Study Details

PMID:30854705
Participants:36
Impact:Test: 0.60→0.39 cm3 (−0.21 cm3, p<0.01); Control: 0.51→0.38 cm3 (−0.13 cm3, p<0.01)
Trust score:4/5

bone density (gray-scale)

1 evidences

Pilot RCT comparing two collagen barrier membranes for guided bone regeneration: both membranes showed graft volume loss and no significant differences between them.

Trust comment: Randomized controlled human trial with objective CBCT measures and high inter-observer reliability but small pilot sample (n=36).

Study Details

PMID:30854705
Participants:36
Impact:Control: 305.12→456.69 (+151.57, p<0.01); Test: 304.75→393.27 (+88.52, p=0.25)
Trust score:4/5

PES/WES (esthetic score)

1 evidences

Pilot RCT comparing two collagen barrier membranes for guided bone regeneration: both membranes showed graft volume loss and no significant differences between them.

Trust comment: Randomized controlled human trial with objective CBCT measures and high inter-observer reliability but small pilot sample (n=36).

Study Details

PMID:30854705
Participants:36
Impact:No significant difference between groups at T1 (13.84 vs 13.90)
Trust score:4/5

Horizontal width loss (at 1 mm)

1 evidences

Compared alveolar ridge preservation methods after extraction and found that bovine bone mineral with collagen membrane and PRGF reduced horizontal and vertical bone loss versus spontaneous healing.

Trust comment: Randomized controlled trial with objective CBCT measures but small sample size per group (four arms) limiting power.

Study Details

PMID:33084205
Participants:40
Impact:Control −1.61 ±1.76 mm vs BBM/CM −0.68 ±0.67 mm (least loss)
Trust score:3/5

Alveolar height reduction

1 evidences

Compared alveolar ridge preservation methods after extraction and found that bovine bone mineral with collagen membrane and PRGF reduced horizontal and vertical bone loss versus spontaneous healing.

Trust comment: Randomized controlled trial with objective CBCT measures but small sample size per group (four arms) limiting power.

Study Details

PMID:33084205
Participants:40
Impact:Control −0.86 ±0.43 mm; BBM/CM −0.26 ±0.91 mm; PRGF −0.54 ±0.86 mm (both BBM/CM and PRGF reduced height loss vs control)
Trust score:3/5

TIMP-1 (collagen matrix marker)

1 evidences

In patients with chronic heart failure and persistent atrial fibrillation, adding omega‑3 PUFA improved arterial elastic properties and reduced a collagen‑matrix marker (TIMP‑1) over 6 months.

Trust comment: Human randomized phase with objective hemodynamic and biomarker endpoints but limited methodological detail and moderate sample size.

Study Details

PMID:23548422
Participants:60
Impact:Decrease in TIMP‑1 (suppression of abnormal collagen formation), p<0.001
Trust score:3/5

Arterial stiffness / elastic properties (pulse wave velocity, CAVI)

1 evidences

In patients with chronic heart failure and persistent atrial fibrillation, adding omega‑3 PUFA improved arterial elastic properties and reduced a collagen‑matrix marker (TIMP‑1) over 6 months.

Trust comment: Human randomized phase with objective hemodynamic and biomarker endpoints but limited methodological detail and moderate sample size.

Study Details

PMID:23548422
Participants:60
Impact:Improved elastic properties / reduced stiffness (significant change, p<0.001)
Trust score:3/5

Solar elastosis

1 evidences

Daylight photodynamic therapy with pretreatment CO2 laser improved clinical and histologic outcomes for photodamaged facial skin, including a significant increase in collagen type I and reduced solar elastosis.

Trust comment: Randomized controlled study with histologic endpoints and paired biopsies, but modest sample size (four small arms) limits generalizability.

Study Details

PMID:34133958
Participants:40
Impact:Reduced in DL‑PDT + CO2 laser group (p=0.034)
Trust score:4/5

Horizontal bone width (HBW) gain

1 evidences

Both guided bone regeneration approaches produced sufficient horizontal ridge augmentation for implants; mean horizontal bone width gains at 18 months were similar and implant survival was 100% in both groups.

Trust comment: Randomized controlled trial with radiographic follow-up and near-complete retention (39 completers); moderate sample size but robust clinical endpoints.

Study Details

PMID:30884111
Participants:39
Impact:GBR + xenograft: +5.6 ±1.35 mm vs ABG+particulate: +4.8 ±0.79 mm at 18 months (no significant difference)
Trust score:4/5

Transforming growth factor‑β (TGF‑β)

1 evidences

Adding Korean Red Ginseng to antiviral therapy in chronic hepatitis B reduced some non‑invasive fibrosis markers (hyaluronic acid and TGF‑β) compared with antivirals alone.

Trust comment: Small, single‑center randomized trial with biomarker endpoints and single‑blinding; findings are promising but limited by size and short follow‑up.

Study Details

PMID:27603149
Participants:38
Impact:Decreased vs control (p=0.008)
Trust score:3/5

Type IV collagen

1 evidences

Adding Korean Red Ginseng to antiviral therapy in chronic hepatitis B reduced some non‑invasive fibrosis markers (hyaluronic acid and TGF‑β) compared with antivirals alone.

Trust comment: Small, single‑center randomized trial with biomarker endpoints and single‑blinding; findings are promising but limited by size and short follow‑up.

Study Details

PMID:27603149
Participants:38
Impact:No significant change (p=0.174)
Trust score:3/5

Scar volume reduction

2 evidences

Single-session split-face trial found both lasers improved acne scar appearance and increased dermal collagen/elastic fibers by 3 months, with fewer PIH events on picosecond side.

Trust comment: Randomized split-face trial with histologic and imaging endpoints but small sample (n=25).

Study Details

PMID:32910030
Participants:25
Impact:significant reduction on both sides (skin imaging)
Trust score:4/5

Fractional CO2 laser produced greater scar improvement than hyaluronidase injections (larger volume reduction, better histologic collagen reorganization and markers of remodeling) in early scars.

Trust comment: Randomized controlled trial with power calculation, blinded outcome assessment, objective 3D imaging and histology; single‑center and moderate sample size but rigorous methodology.

Study Details

PMID:40536647
Participants:56
Impact:CO2 laser 45.3% ±12.4% vs hyaluronidase 32.7% ±11.8% at 6 months (p<0.001)
Trust score:4/5

MMP-1 expression (matrix remodeling)

1 evidences

Fractional CO2 laser produced greater scar improvement than hyaluronidase injections (larger volume reduction, better histologic collagen reorganization and markers of remodeling) in early scars.

Trust comment: Randomized controlled trial with power calculation, blinded outcome assessment, objective 3D imaging and histology; single‑center and moderate sample size but rigorous methodology.

Study Details

PMID:40536647
Participants:56
Impact:Higher with CO2 laser (2.4 ±0.5 vs 1.6 ±0.4, p=0.015)
Trust score:4/5

TGF-β1 and Type I/III collagen ratio

1 evidences

Fractional CO2 laser produced greater scar improvement than hyaluronidase injections (larger volume reduction, better histologic collagen reorganization and markers of remodeling) in early scars.

Trust comment: Randomized controlled trial with power calculation, blinded outcome assessment, objective 3D imaging and histology; single‑center and moderate sample size but rigorous methodology.

Study Details

PMID:40536647
Participants:56
Impact:Lower TGF‑β1 (1.7 vs 2.3, p=0.024) and lower Type I/III ratio (2.8 vs 3.4, p=0.022) with CO2 laser
Trust score:4/5

Bucco-lingual alveolar width change

1 evidences

Randomized clinical trial (26 completers) comparing synthetic bone substitute vs bovine-derived xenograft, both covered with a collagen membrane; both preserved ridge height but bucco-lingual width decreased less with the synthetic material.

Trust comment: Randomized controlled trial with 26 completers and histologic analyses; moderate sample size limits precision.

Study Details

PMID:20636724
Participants:26
Impact:SBC (synthetic) -1.1 ± 1.0 mm; DBBM (bovine) -2.1 ± 1.0 mm (P < 0.05)
Trust score:3/5

Interproximal (mesio-distal) bone height

1 evidences

Randomized clinical trial (26 completers) comparing synthetic bone substitute vs bovine-derived xenograft, both covered with a collagen membrane; both preserved ridge height but bucco-lingual width decreased less with the synthetic material.

Trust comment: Randomized controlled trial with 26 completers and histologic analyses; moderate sample size limits precision.

Study Details

PMID:20636724
Participants:26
Impact:preserved in both groups (no meaningful change reported)
Trust score:3/5

New bone formation (histology)

1 evidences

Randomized clinical trial (26 completers) comparing synthetic bone substitute vs bovine-derived xenograft, both covered with a collagen membrane; both preserved ridge height but bucco-lingual width decreased less with the synthetic material.

Trust comment: Randomized controlled trial with 26 completers and histologic analyses; moderate sample size limits precision.

Study Details

PMID:20636724
Participants:26
Impact:new bone present in apical biopsy regions in both groups
Trust score:3/5

Primary endpoint (pseudoaneurysm/major bleeding/vascular surgery/death) incidence

1 evidences

Large randomized study (n=852) comparing collagen-plug closure device, clip device, and wound dressing after femoral artery access; collagen plug had the lowest complication rates.

Trust comment: Large randomized trial with robust sample size and clinically relevant endpoints, increasing confidence in findings.

Study Details

PMID:18254672
Participants:852
Impact:D-Stat Dry 7.1% (20/281) vs mechanical closures 1.9% (11/571); Angio-Seal (collagen plug) 1.1% vs StarClose 2.8% (p=0.13 between devices)
Trust score:5/5

Access-site complication rates (major + minor)

1 evidences

Large randomized study (n=852) comparing collagen-plug closure device, clip device, and wound dressing after femoral artery access; collagen plug had the lowest complication rates.

Trust comment: Large randomized trial with robust sample size and clinically relevant endpoints, increasing confidence in findings.

Study Details

PMID:18254672
Participants:852
Impact:lowest with collagen plug device (Angio-Seal) compared with wound dressing and similar to other mechanical device
Trust score:5/5

collagen turnover (urinary NTx)

1 evidences

In children with new atopic asthma, adding vitamin D to high-dose inhaled corticosteroids improved markers of calcium-phosphorus balance and reduced a urine marker of bone degradation over 6 months.

Trust comment: Randomized, double-blind trial with biochemical endpoints and adequate sample size for pediatric population.

Study Details

PMID:21251993
Participants:96
Impact:decrease (significant) in ICS 800 + vitamin D group
Trust score:4/5

phosphorus and PTH serum levels

1 evidences

In children with new atopic asthma, adding vitamin D to high-dose inhaled corticosteroids improved markers of calcium-phosphorus balance and reduced a urine marker of bone degradation over 6 months.

Trust comment: Randomized, double-blind trial with biochemical endpoints and adequate sample size for pediatric population.

Study Details

PMID:21251993
Participants:96
Impact:decrease (significant) in ICS 400 and ICS 800 + vitamin D groups vs control
Trust score:4/5

uterine fibroid risk

1 evidences

Genetic variants in collagen-family genes were associated with both risk of uterine fibroids and increased tumor size in a large premenopausal cohort.

Trust comment: Large case-control genetic association study with replication across ancestry groups, supporting credible associations.

Study Details

PMID:25455875
Participants:1045
Impact:significant association with variants in collagen gene family (e.g., COL6A3, COL13A)
Trust score:4/5

tumor size

1 evidences

Genetic variants in collagen-family genes were associated with both risk of uterine fibroids and increased tumor size in a large premenopausal cohort.

Trust comment: Large case-control genetic association study with replication across ancestry groups, supporting credible associations.

Study Details

PMID:25455875
Participants:1045
Impact:significant association with collagen gene variants (affecting tumor size)
Trust score:4/5

modified Cincinnati knee score

1 evidences

Both ACI with a porcine type I/III collagen cover and MACI (collagen bilayer) produced comparable clinical, arthroscopic and histological improvements at one year.

Trust comment: Prospective randomized study comparing collagen-based cartilage repair techniques with clinical, arthroscopic and histological endpoints.

Study Details

PMID:15855365
Participants:91
Impact:+17.6 (ACI-C) and +19.6 (MACI) at 1 year; p=0.32
Trust score:4/5

hyaline-like cartilage on biopsy

1 evidences

Both ACI with a porcine type I/III collagen cover and MACI (collagen bilayer) produced comparable clinical, arthroscopic and histological improvements at one year.

Trust comment: Prospective randomized study comparing collagen-based cartilage repair techniques with clinical, arthroscopic and histological endpoints.

Study Details

PMID:15855365
Participants:91
Impact:43.9% (ACI-C) vs 36.4% (MACI) at 1 year
Trust score:4/5

graft hypertrophy rate

1 evidences

Both ACI with a porcine type I/III collagen cover and MACI (collagen bilayer) produced comparable clinical, arthroscopic and histological improvements at one year.

Trust comment: Prospective randomized study comparing collagen-based cartilage repair techniques with clinical, arthroscopic and histological endpoints.

Study Details

PMID:15855365
Participants:91
Impact:9% (ACI-C) vs 6% (MACI)
Trust score:4/5

marginal peri-implant recession

1 evidences

In immediate implant placement, connective tissue grafts prevented marginal peri-implant recession and improved soft tissue contour and thickness; a collagen matrix group was included but its effects were not clearly reported in the abstract.

Trust comment: Small randomized trial with direct use of a collagen matrix but limited sample size and incomplete reporting of collagen-matrix-specific outcomes.

Study Details

PMID:29677227
Participants:24
Impact:avoided by connective tissue graft (P<0.05); collagen matrix effect not clearly reported
Trust score:3/5

soft tissue thickness/contour

1 evidences

In immediate implant placement, connective tissue grafts prevented marginal peri-implant recession and improved soft tissue contour and thickness; a collagen matrix group was included but its effects were not clearly reported in the abstract.

Trust comment: Small randomized trial with direct use of a collagen matrix but limited sample size and incomplete reporting of collagen-matrix-specific outcomes.

Study Details

PMID:29677227
Participants:24
Impact:improved with connective tissue graft (P<0.01 for contour, P<0.05 for thickness); collagen matrix effect not specified
Trust score:3/5

collagen‑induced platelet aggregation

2 evidences

In hip surgery patients, surgery increased thrombin generation and platelet activation causing reduced aggregation overall; albumin infusion specifically inhibited collagen‑induced platelet aggregation.

Trust comment: Randomized, double‑blind RCT with 55 patients and biologic endpoints; effects on collagen responses reported but numeric magnitudes for collagen inhibition not provided.

Study Details

PMID:14521596
Participants:55
Impact:inhibited by albumin (no numeric value reported)
Trust score:3/5

In hypertensive patients, quinapril (ACE inhibitor) improved measures of platelet function including parameters of collagen‑induced aggregation and reduced beta‑thromboglobulin, whereas nifedipine did not.

Trust comment: Investigator‑blind randomized trial with 40 patients; platelet outcomes reported but numeric magnitudes for collagen effects are not provided.

Study Details

PMID:11487379
Participants:40
Impact:improved in quinapril group (no numeric value reported)
Trust score:3/5

platelet activation (beta‑TG)

1 evidences

In hip surgery patients, surgery increased thrombin generation and platelet activation causing reduced aggregation overall; albumin infusion specifically inhibited collagen‑induced platelet aggregation.

Trust comment: Randomized, double‑blind RCT with 55 patients and biologic endpoints; effects on collagen responses reported but numeric magnitudes for collagen inhibition not provided.

Study Details

PMID:14521596
Participants:55
Impact:increased during surgery (persistent platelet desensitization)
Trust score:3/5

thrombin generation markers

1 evidences

In hip surgery patients, surgery increased thrombin generation and platelet activation causing reduced aggregation overall; albumin infusion specifically inhibited collagen‑induced platelet aggregation.

Trust comment: Randomized, double‑blind RCT with 55 patients and biologic endpoints; effects on collagen responses reported but numeric magnitudes for collagen inhibition not provided.

Study Details

PMID:14521596
Participants:55
Impact:increased during surgery (F1+2, TAT increases)
Trust score:3/5

collagen‑induced platelet aggregation (1 µg/ml)

1 evidences

After CABG, low‑dose aspirin (50 mg/day) produced sustained inhibition of platelet aggregation induced by collagen and markedly reduced thromboxane B2 synthesis in vitro.

Trust comment: Prospective randomized trial in 42 patients showing large biochemical platelet effects; moderate sample and clinical context support reliability for platelet outcomes.

Study Details

PMID:9885179
Participants:42
Impact:inhibited >50% after 3–6 months
Trust score:3/5

collagen‑induced platelet aggregation (5 µg/ml)

1 evidences

After CABG, low‑dose aspirin (50 mg/day) produced sustained inhibition of platelet aggregation induced by collagen and markedly reduced thromboxane B2 synthesis in vitro.

Trust comment: Prospective randomized trial in 42 patients showing large biochemical platelet effects; moderate sample and clinical context support reliability for platelet outcomes.

Study Details

PMID:9885179
Participants:42
Impact:~20% inhibition (not significant)
Trust score:3/5

thromboxane B2 synthesis

1 evidences

After CABG, low‑dose aspirin (50 mg/day) produced sustained inhibition of platelet aggregation induced by collagen and markedly reduced thromboxane B2 synthesis in vitro.

Trust comment: Prospective randomized trial in 42 patients showing large biochemical platelet effects; moderate sample and clinical context support reliability for platelet outcomes.

Study Details

PMID:9885179
Participants:42
Impact:reduced to ~1% of baseline (p ≤ 0.01)
Trust score:3/5

beta‑thromboglobulin

1 evidences

In hypertensive patients, quinapril (ACE inhibitor) improved measures of platelet function including parameters of collagen‑induced aggregation and reduced beta‑thromboglobulin, whereas nifedipine did not.

Trust comment: Investigator‑blind randomized trial with 40 patients; platelet outcomes reported but numeric magnitudes for collagen effects are not provided.

Study Details

PMID:11487379
Participants:40
Impact:decreased significantly in quinapril group
Trust score:3/5

serum 25‑hydroxyvitamin D (s25D)

1 evidences

Obese women had lower serum 25-hydroxyvitamin D and higher PTH; low vitamin D was not associated with comorbid conditions except osteoarthritis.

Trust comment: Case‑control study with 98 participants and multiple biochemical measures; moderate quality but observational design limits causal inference regarding collagen markers.

Study Details

PMID:21325456
Participants:98
Impact:lower in bariatric surgery group versus controls (no numeric value reported)
Trust score:3/5

serum PTH (sPTH)

1 evidences

Obese women had lower serum 25-hydroxyvitamin D and higher PTH; low vitamin D was not associated with comorbid conditions except osteoarthritis.

Trust comment: Case‑control study with 98 participants and multiple biochemical measures; moderate quality but observational design limits causal inference regarding collagen markers.

Study Details

PMID:21325456
Participants:98
Impact:higher in bariatric surgery group (no numeric value reported)
Trust score:3/5

serum cross‑linked N‑telopeptides of type I collagen

1 evidences

Obese women had lower serum 25-hydroxyvitamin D and higher PTH; low vitamin D was not associated with comorbid conditions except osteoarthritis.

Trust comment: Case‑control study with 98 participants and multiple biochemical measures; moderate quality but observational design limits causal inference regarding collagen markers.

Study Details

PMID:21325456
Participants:98
Impact:measured as bone turnover marker (no clear between‑group effect reported)
Trust score:3/5

mucosal (soft tissue) thickness

1 evidences

Exploratory RCT: using DBBM-C (xenogenic bone with 10% collagen) ± collagen matrix for ridge preservation increased soft tissue thickness and reduced invaginations and need for augmentation versus spontaneous healing at 8 weeks.

Trust comment: Randomized exploratory RCT with objective outcomes but small sample (N=36) limits generalizability.

Study Details

PMID:32128884
Participants:36
Impact:median 3.0 mm (DBBM-C/CM) vs 2.1 mm (DBBM-C) vs 1.5 mm (spontaneous healing) at 8 weeks
Trust score:3/5

soft-tissue invagination rate

1 evidences

Exploratory RCT: using DBBM-C (xenogenic bone with 10% collagen) ± collagen matrix for ridge preservation increased soft tissue thickness and reduced invaginations and need for augmentation versus spontaneous healing at 8 weeks.

Trust comment: Randomized exploratory RCT with objective outcomes but small sample (N=36) limits generalizability.

Study Details

PMID:32128884
Participants:36
Impact:41.7% (DBBM-C/CM) vs 53.8% (DBBM-C) vs 90.9% (spontaneous healing)
Trust score:3/5

need for additional guided bone regeneration (GBR)

1 evidences

Exploratory RCT: using DBBM-C (xenogenic bone with 10% collagen) ± collagen matrix for ridge preservation increased soft tissue thickness and reduced invaginations and need for augmentation versus spontaneous healing at 8 weeks.

Trust comment: Randomized exploratory RCT with objective outcomes but small sample (N=36) limits generalizability.

Study Details

PMID:32128884
Participants:36
Impact:66.7% (DBBM-C/CM) vs 53.8% (DBBM-C) vs 90.9% (spontaneous healing)
Trust score:3/5

horizontal bone resorption (1 mm below crest)

1 evidences

Randomized controlled trial comparing DBBM-C + collagen matrix, DBBM-C + palatal graft, and spontaneous healing: ARP with collagen matrix reduced horizontal/vertical bone loss and reduced need for additional augmentation at 8 weeks.

Trust comment: Well-conducted randomized trial (N=75) with concealed allocation and blinded outcome assessment; short follow-up (8 weeks) but overall moderate-high quality.

Study Details

PMID:33217058
Participants:75
Impact:median change −1.0 mm (CM) vs −2.5 mm (control); CM vs control MD 2.3 mm (p<0.001)
Trust score:4/5

vertical buccal crest change

1 evidences

Randomized controlled trial comparing DBBM-C + collagen matrix, DBBM-C + palatal graft, and spontaneous healing: ARP with collagen matrix reduced horizontal/vertical bone loss and reduced need for additional augmentation at 8 weeks.

Trust comment: Well-conducted randomized trial (N=75) with concealed allocation and blinded outcome assessment; short follow-up (8 weeks) but overall moderate-high quality.

Study Details

PMID:33217058
Participants:75
Impact:mean change −0.8 mm (CM) vs −1.9 mm (control); CM vs control MD ~1.5 mm (p<0.001)
Trust score:4/5

need for additional GBR at implant placement

1 evidences

Randomized controlled trial comparing DBBM-C + collagen matrix, DBBM-C + palatal graft, and spontaneous healing: ARP with collagen matrix reduced horizontal/vertical bone loss and reduced need for additional augmentation at 8 weeks.

Trust comment: Well-conducted randomized trial (N=75) with concealed allocation and blinded outcome assessment; short follow-up (8 weeks) but overall moderate-high quality.

Study Details

PMID:33217058
Participants:75
Impact:32% (CM) vs 72% (control); PG 24% (significant differences)
Trust score:4/5

fracture healing (week 13)

1 evidences

Adding rhBMP-2 delivered on an absorbable collagen sponge did not significantly accelerate fracture healing and showed a non‑significant trend toward higher infection.

Trust comment: Large randomized human trial using an absorbable collagen sponge as a delivery matrix; relevant to collagen-containing medical devices though the active agent was rhBMP-2.

Study Details

PMID:21454742
Participants:277
Impact:60% vs 48% healed in rhBMP-2/ACS vs SOC (p=0.0541, borderline)
Trust score:3/5

fracture healing (week 20)

1 evidences

Adding rhBMP-2 delivered on an absorbable collagen sponge did not significantly accelerate fracture healing and showed a non‑significant trend toward higher infection.

Trust comment: Large randomized human trial using an absorbable collagen sponge as a delivery matrix; relevant to collagen-containing medical devices though the active agent was rhBMP-2.

Study Details

PMID:21454742
Participants:277
Impact:68% vs 67% healed (no significant difference)
Trust score:3/5

DNA content (healing marker)

1 evidences

Randomized trial after hip replacement: added activity increased DNA content in subcutaneous implant but did not improve collagen markers or wound-healing measures.

Trust comment: Small randomized clinical trial with objective tissue assays but limited sample size and short follow-up.

Study Details

PMID:15388905
Participants:58
Impact:increased (statistically significant; exact values not provided)
Trust score:3/5

pro-collagen mRNA / hydroxyproline (collagen measures)

1 evidences

Randomized trial after hip replacement: added activity increased DNA content in subcutaneous implant but did not improve collagen markers or wound-healing measures.

Trust comment: Small randomized clinical trial with objective tissue assays but limited sample size and short follow-up.

Study Details

PMID:15388905
Participants:58
Impact:no increase (no numeric change reported)
Trust score:3/5

tissue oxygenation (PscO2) and perfusion

1 evidences

Randomized trial after hip replacement: added activity increased DNA content in subcutaneous implant but did not improve collagen markers or wound-healing measures.

Trust comment: Small randomized clinical trial with objective tissue assays but limited sample size and short follow-up.

Study Details

PMID:15388905
Participants:58
Impact:no change (no numeric change reported)
Trust score:3/5

axillary drainage duration

1 evidences

Prospective randomized trial of a fibrin-glue coated collagen patch vs standard closure after axillary lymphadenectomy found no significant differences in drainage duration, drainage volume, hospital stay, local inflammation, or seroma formation.

Trust comment: Prospective randomized controlled trial with clear numeric outcomes but modest sample size and open-label design.

Study Details

PMID:11518470
Participants:60
Impact:no significant difference (3.8 ± 1.9 vs 3.9 ± 1.8 days; −0.1 days)
Trust score:4/5

total drainage volume

1 evidences

Prospective randomized trial of a fibrin-glue coated collagen patch vs standard closure after axillary lymphadenectomy found no significant differences in drainage duration, drainage volume, hospital stay, local inflammation, or seroma formation.

Trust comment: Prospective randomized controlled trial with clear numeric outcomes but modest sample size and open-label design.

Study Details

PMID:11518470
Participants:60
Impact:no significant difference (338.5 ± 251.8 vs 370.8 ± 314.6 ml; −32.3 ml)
Trust score:4/5

postoperative hospital stay

1 evidences

Prospective randomized trial of a fibrin-glue coated collagen patch vs standard closure after axillary lymphadenectomy found no significant differences in drainage duration, drainage volume, hospital stay, local inflammation, or seroma formation.

Trust comment: Prospective randomized controlled trial with clear numeric outcomes but modest sample size and open-label design.

Study Details

PMID:11518470
Participants:60
Impact:no significant difference (9.1 ± 2.7 vs 9.3 ± 3.6 days)
Trust score:4/5

interproximal radiographic bone levels / clinical measures

1 evidences

Randomized clinical study of two graft materials with the same collagen barrier showed 100% implant survival and similar clinical and radiographic outcomes at 1-year post-loading.

Trust comment: Small randomized clinical study; collagen barrier was used in both arms so it does not isolate collagen effect.

Study Details

PMID:22672611
Participants:27
Impact:no significant differences detected
Trust score:3/5

aesthetic improvement (GAIS)

1 evidences

Some patients had modest lasting cosmetic improvement and no long-term side effects up to three years after treatment.

Trust comment: Extension of a randomized split-face clinical study with 102 patients and long (3-year) follow-up supports reliability, though it is an extension analysis.

Study Details

PMID:20442101
Participants:102
Impact:40% of folds rated "improved" or better at ≥30 months after last Radiesse injection
Trust score:4/5

long-term adverse events

2 evidences

Compared autogenous basilic-brachial AVF to collagen-polyester prosthetic graft (Omniflow II) for hemodialysis access; prosthetic graft had quicker use but worse long-term outcomes.

Trust comment: Randomized comparison with moderate sample size; relevant to a collagen-containing prosthesis but limited power and detail for effect sizes.

Study Details

PMID:21803519
Participants:57
Impact:higher with collagen-polyester AVG (vs BBAVF; not quantified)
Trust score:3/5

Some patients had modest lasting cosmetic improvement and no long-term side effects up to three years after treatment.

Trust comment: Extension of a randomized split-face clinical study with 102 patients and long (3-year) follow-up supports reliability, though it is an extension analysis.

Study Details

PMID:20442101
Participants:102
Impact:0 long-term or delayed-onset adverse events reported in 102 patients over 3 years
Trust score:4/5

clinical and esthetic outcome (PES/WES, clinical indices)

1 evidences

Both grafting approaches using a collagen membrane produced stable clinical and esthetic results with all implants clinically successful at 1 year.

Trust comment: Randomized two-center clinical trial with objective clinical and esthetic measures and complete 1-year outcomes supports moderate-to-high reliability.

Study Details

PMID:30367723
Participants:48
Impact:No significant differences between groups; PES/WES totals ~15.29 vs 15.33 at 1 year (stable outcomes)
Trust score:4/5

implant clinical success rate

1 evidences

Both grafting approaches using a collagen membrane produced stable clinical and esthetic results with all implants clinically successful at 1 year.

Trust comment: Randomized two-center clinical trial with objective clinical and esthetic measures and complete 1-year outcomes supports moderate-to-high reliability.

Study Details

PMID:30367723
Participants:48
Impact:All 48 implants clinically successful at 1-year follow-up
Trust score:4/5

Bucco-oral tissue loss after extraction

1 evidences

After tooth extraction, using DBBM with a soft tissue punch or adding an absorbable collagen membrane limited bucco-oral tissue loss compared with DBBM alone or no treatment at 6 months.

Trust comment: Randomized clinical study in humans that included an absorbable collagen membrane (Osseoguard); moderate sample size but limited quantitative detail.

Study Details

PMID:28402351
Participants:35
Impact:reduced (significant) with DBBM+soft tissue punch or DBBM+collagen membrane vs DBBM alone/control
Trust score:3/5

Need for further bone augmentation

1 evidences

After tooth extraction, using DBBM with a soft tissue punch or adding an absorbable collagen membrane limited bucco-oral tissue loss compared with DBBM alone or no treatment at 6 months.

Trust comment: Randomized clinical study in humans that included an absorbable collagen membrane (Osseoguard); moderate sample size but limited quantitative detail.

Study Details

PMID:28402351
Participants:35
Impact:reduced (reported, not quantified)
Trust score:3/5

Bone quality

1 evidences

After tooth extraction, using DBBM with a soft tissue punch or adding an absorbable collagen membrane limited bucco-oral tissue loss compared with DBBM alone or no treatment at 6 months.

Trust comment: Randomized clinical study in humans that included an absorbable collagen membrane (Osseoguard); moderate sample size but limited quantitative detail.

Study Details

PMID:28402351
Participants:35
Impact:assessed (no quantitative summary provided)
Trust score:3/5

dermal collagen

1 evidences

Combination of botulinum toxin type A and full-face broadband light produced better cosmetic improvement than light alone and skin biopsies showed increased dermal collagen.

Trust comment: Randomized study with clinical and histologic endpoints but small sample and biopsies were performed in only two subjects per group, limiting generalizability.

Study Details

PMID:15008861
Participants:30
Impact:+increase (histologic)
Trust score:3/5

dermal collagen I

1 evidences

Both low-dose oral isotretinoin and topical retinoic acid improved photoaging and were associated with increased dermal collagen type I on immunohistochemistry, with no difference between treatments.

Trust comment: Randomized, evaluator-blinded study with histologic and immunohistochemical endpoints but small sample (24 randomized, 22 completed), limiting power.

Study Details

PMID:24168514
Participants:22
Impact:+increase (immunohistochemical)
Trust score:3/5

WOMAC composite score

1 evidences

12-week randomized double-blind trial of water-soluble eggshell membrane (contains collagen and GAGs) in knee OA found early reduction in stiffness (day 5) and improved individual 6-minute walk performance by day 84, but no between-group difference in overall WOMAC composite scores.

Trust comment: Randomized, double-blind, placebo-controlled human trial (n=88 randomized, 80 completed) showing modest objective and subjective benefits; single-site and some outcome limitations reduce but do not negate trust.

Study Details

PMID:31381494
Participants:80
Impact:No significant difference between Study Product and Placebo at any time point
Trust score:4/5

WOMAC-stiffness subscale

1 evidences

12-week randomized double-blind trial of water-soluble eggshell membrane (contains collagen and GAGs) in knee OA found early reduction in stiffness (day 5) and improved individual 6-minute walk performance by day 84, but no between-group difference in overall WOMAC composite scores.

Trust comment: Randomized, double-blind, placebo-controlled human trial (n=88 randomized, 80 completed) showing modest objective and subjective benefits; single-site and some outcome limitations reduce but do not negate trust.

Study Details

PMID:31381494
Participants:80
Impact:Significant reduction by day 5 in Study Product vs Placebo (P < 0.05)
Trust score:4/5

Six-minute walk test (average individual improvement)

1 evidences

12-week randomized double-blind trial of water-soluble eggshell membrane (contains collagen and GAGs) in knee OA found early reduction in stiffness (day 5) and improved individual 6-minute walk performance by day 84, but no between-group difference in overall WOMAC composite scores.

Trust comment: Randomized, double-blind, placebo-controlled human trial (n=88 randomized, 80 completed) showing modest objective and subjective benefits; single-site and some outcome limitations reduce but do not negate trust.

Study Details

PMID:31381494
Participants:80
Impact:Greater improvement in Study Product group by day 84 (difference P = 0.0273)
Trust score:4/5

graft patency

1 evidences

Randomized trial comparing woven vs collagen-impregnated knitted Dacron arterial grafts; knitted grafts had lower intraoperative blood loss but otherwise similar performance and patency at 1 year.

Trust comment: Large randomized trial with 267 patients and 1-year follow-up; pragmatic surgical endpoints and statistically reported differences give moderate-high trust.

Study Details

PMID:9667705
Participants:267
Impact:no difference at discharge and 1 year
Trust score:4/5

distal anastomosis graft diameter

1 evidences

Randomized trial comparing woven vs collagen-impregnated knitted Dacron arterial grafts; knitted grafts had lower intraoperative blood loss but otherwise similar performance and patency at 1 year.

Trust comment: Large randomized trial with 267 patients and 1-year follow-up; pragmatic surgical endpoints and statistically reported differences give moderate-high trust.

Study Details

PMID:9667705
Participants:267
Impact:non-significant increase in knitted group ~1.2 mm (mean, 1-year)
Trust score:4/5

mid-facial mucosal level change (MLC)

1 evidences

Randomized trial comparing DBBM vs DBBM + 10% collagen for alveolar ridge preservation; overall mid-facial mucosal level and long-term tissue stability similar between materials, with some early soft tissue thickness advantage for DBBM alone.

Trust comment: Randomized clinical trial with 66 treated and 54 analyzed, one-year post-restoration follow-up and objective measures—reasonable quality though moderate sample size.

Study Details

PMID:34708422
Participants:54
Impact:no statistical difference between DBBM and DBBM-C (T0–T1 and T1–T2)
Trust score:4/5

soft tissue thickness

3 evidences

Acellular dermal matrix (ADM) produced more collagen fibers but showed greater tissue shrinkage and delayed healing compared with free gingival grafts.

Trust comment: Small split‑mouth randomized trial with histology supporting findings but limited sample size and some outcomes lacking numeric detail.

Study Details

PMID:29713889
Participants:25
Impact:Reduced (ADM inferior to FGG; no numeric value reported)
Trust score:3/5

RCT comparing immediate implants with or without DBBM-C (10% collagen); adding DBBM-C slightly reduced tissue dimensional changes with one significant benefit at the distal papilla.

Trust comment: Prospective randomized controlled clinical trial with complete 12-month follow-up but modest sample size (n=32).

Study Details

PMID:31815977
Participants:32
Impact:no significant change between groups
Trust score:4/5

Randomized trial comparing DBBM vs DBBM + 10% collagen for alveolar ridge preservation; overall mid-facial mucosal level and long-term tissue stability similar between materials, with some early soft tissue thickness advantage for DBBM alone.

Trust comment: Randomized clinical trial with 66 treated and 54 analyzed, one-year post-restoration follow-up and objective measures—reasonable quality though moderate sample size.

Study Details

PMID:34708422
Participants:54
Impact:DBBM showed significantly greater thickness at 3 and 5 mm (T0–T1); no differences T1–T2
Trust score:4/5

quadriceps muscle volume

1 evidences

In a 15-week randomized double-blind trial, daily 15 g collagen peptide supplementation with resistance training increased muscle hypertrophy and evoked twitch torque but did not augment voluntary strength versus placebo.

Trust comment: Randomized double-blind placebo-controlled human trial with MRI muscle-volume outcomes and objective contractile measures; moderate sample and funded by a collagen-focused institute.

Study Details

PMID:36433662
Participants:39
Impact:+15.2% (CP) vs +10.3% (PLA) % change after 15 weeks
Trust score:4/5

total trained muscle volume

1 evidences

In a 15-week randomized double-blind trial, daily 15 g collagen peptide supplementation with resistance training increased muscle hypertrophy and evoked twitch torque but did not augment voluntary strength versus placebo.

Trust comment: Randomized double-blind placebo-controlled human trial with MRI muscle-volume outcomes and objective contractile measures; moderate sample and funded by a collagen-focused institute.

Study Details

PMID:36433662
Participants:39
Impact:+15.7% (CP) vs +11.4% (PLA) % change after 15 weeks
Trust score:4/5

evoked twitch peak torque

1 evidences

In a 15-week randomized double-blind trial, daily 15 g collagen peptide supplementation with resistance training increased muscle hypertrophy and evoked twitch torque but did not augment voluntary strength versus placebo.

Trust comment: Randomized double-blind placebo-controlled human trial with MRI muscle-volume outcomes and objective contractile measures; moderate sample and funded by a collagen-focused institute.

Study Details

PMID:36433662
Participants:39
Impact:+22.3% (CP) vs +12.3% (PLA) % change after 15 weeks; between-group difference p=0.038
Trust score:4/5

Heme iron bioavailability — red blood cell concentrate (RBCC)

1 evidences

In controlled absorption studies in women, purified collagen (and other isolated animal proteins) did not change heme iron bioavailability, whereas red blood cell concentrate increased it and mixing heme with fish or chicken reduced it.

Trust comment: Controlled human absorption studies with modest sample size and clear quantitative outcomes; applicable to dietary interactions but not a supplementation efficacy trial.

Study Details

PMID:26593548
Participants:45
Impact:25.0% (≈2-fold higher vs heme alone ~13.0%)
Trust score:3/5

Heme iron bioavailability — heme + fish/chicken

1 evidences

In controlled absorption studies in women, purified collagen (and other isolated animal proteins) did not change heme iron bioavailability, whereas red blood cell concentrate increased it and mixing heme with fish or chicken reduced it.

Trust comment: Controlled human absorption studies with modest sample size and clear quantitative outcomes; applicable to dietary interactions but not a supplementation efficacy trial.

Study Details

PMID:26593548
Participants:45
Impact:Fish: 7.1% (decrease vs heme alone); Chicken: 4.9% (decrease vs heme alone)
Trust score:3/5

Heme iron bioavailability — purified proteins (casein, collagen, albumin)

1 evidences

In controlled absorption studies in women, purified collagen (and other isolated animal proteins) did not change heme iron bioavailability, whereas red blood cell concentrate increased it and mixing heme with fish or chicken reduced it.

Trust comment: Controlled human absorption studies with modest sample size and clear quantitative outcomes; applicable to dietary interactions but not a supplementation efficacy trial.

Study Details

PMID:26593548
Participants:45
Impact:No effect (no change vs heme alone)
Trust score:3/5

keratinized gingiva width

1 evidences

In 22 patients, autologous concentrated growth factor (CGF) membranes produced faster soft-tissue healing and higher microvessel density than Bio-Gide collagen membranes, while alveolar bone preservation was similar between groups.

Trust comment: Randomized controlled trial in humans comparing CGF to collagen membrane with objective measures but small sample (22 patients) limits generalizability.

Study Details

PMID:36316617
Participants:22
Impact:No significant difference (CGF 0.985 mm vs Bio-Gide 0.833 mm, P=0.599)
Trust score:4/5

finger joint contracture

1 evidences

Enzyme (collagenase) injections that break down excess collagen reduced finger contractures and were safe in most patients.

Trust comment: Randomized, placebo-controlled phase-2 trials with moderate sample size showing clinical benefit, though full phase-3 data not reported.

Study Details

PMID:12239666
Participants:129
Impact:reduced in majority of patients (clinical improvement)
Trust score:4/5

MMP-1 (matrix metalloproteinase-1)

1 evidences

Higher blood markers of collagen turnover were linked to worse walking distance and higher risk of death or hospitalization in chronic heart failure patients.

Trust comment: Large, well-conducted observational cohort with multivariable adjustment linking collagen turnover markers to functional outcomes and prognosis.

Study Details

PMID:18672194
Participants:1009
Impact:higher MMP-1 independently associated with decreased 6-minute walk distance
Trust score:4/5

PICP (propeptide of type-I collagen)

1 evidences

Long-term alfacalcidol (vitamin D analog) increased bone mineral density at spine and hip and lowered parathyroid hormone and bone turnover markers in pre-dialysis CRF patients.

Trust comment: Randomized, double-blind, placebo-controlled trial but small sample size (n=36) limits precision despite clear biochemical and BMD effects.

Study Details

PMID:15031343
Participants:36
Impact:placebo group ↑ by 32% (alfacalcidol group showed no such increase)
Trust score:4/5

mesial bone level (bone loss)

1 evidences

Immediate implants with or without anorganic bovine bone + resorbable collagen barrier were compared over 3 years; no difference in implant failures but graft+collagen group showed greater marginal bone loss and worse esthetic/patient satisfaction.

Trust comment: Multicenter randomized controlled trial with 3‑year follow‑up and objective measures, but moderate sample size and mixed implant counts.

Study Details

PMID:30260821
Participants:102
Impact:-0.61 mm (no graft) vs -1.01 mm (graft); graft group ~0.40 mm greater loss
Trust score:4/5

Pink Esthetic Score / patient satisfaction

1 evidences

Immediate implants with or without anorganic bovine bone + resorbable collagen barrier were compared over 3 years; no difference in implant failures but graft+collagen group showed greater marginal bone loss and worse esthetic/patient satisfaction.

Trust comment: Multicenter randomized controlled trial with 3‑year follow‑up and objective measures, but moderate sample size and mixed implant counts.

Study Details

PMID:30260821
Participants:102
Impact:higher in no-graft group (P < 0.001)
Trust score:4/5

post-operative infection rate

1 evidences

Insertion of Gentacoll (collagen sponge with gentamicin) after mastectomy reduced infections, seromas, drainage volumes and hospital stay versus control.

Trust comment: Randomized prospective trial directly testing a collagen-based implant (Gentacoll) with clear clinical endpoints but modest sample size (n=44).

Study Details

PMID:20926017
Participants:44
Impact:reduced in Gentacoll group (statistically significant)
Trust score:3/5

drainage volumes

1 evidences

Insertion of Gentacoll (collagen sponge with gentamicin) after mastectomy reduced infections, seromas, drainage volumes and hospital stay versus control.

Trust comment: Randomized prospective trial directly testing a collagen-based implant (Gentacoll) with clear clinical endpoints but modest sample size (n=44).

Study Details

PMID:20926017
Participants:44
Impact:reduced in Gentacoll group (statistically significant)
Trust score:3/5

duration of hospital stay

1 evidences

Insertion of Gentacoll (collagen sponge with gentamicin) after mastectomy reduced infections, seromas, drainage volumes and hospital stay versus control.

Trust comment: Randomized prospective trial directly testing a collagen-based implant (Gentacoll) with clear clinical endpoints but modest sample size (n=44).

Study Details

PMID:20926017
Participants:44
Impact:reduced in Gentacoll group (statistically significant)
Trust score:3/5

Steepest keratometry (Kmax)

1 evidences

In 50 patients with bilateral progressive keratoconus, continuous and pulsed accelerated corneal collagen cross-linking with supplemental oxygen produced comparable improvements in corneal topography and biomechanics at one year.

Trust comment: Prospective randomized paired-eye study with 12-month follow-up and objective measures, though right/left-eye allocation and single-center design limit generalizability.

Study Details

PMID:38162570
Participants:50
Impact:P-KXL: −1.5 D (p=0.03); C-KXL: −1.2 D (p=0.043) at 1 year
Trust score:4/5

Average keratometry (Km)

1 evidences

In 50 patients with bilateral progressive keratoconus, continuous and pulsed accelerated corneal collagen cross-linking with supplemental oxygen produced comparable improvements in corneal topography and biomechanics at one year.

Trust comment: Prospective randomized paired-eye study with 12-month follow-up and objective measures, though right/left-eye allocation and single-center design limit generalizability.

Study Details

PMID:38162570
Participants:50
Impact:P-KXL: −1.01 D (p=0.04); C-KXL: −1.11 D (p=0.031) at 1 year
Trust score:4/5

Corneal biomechanical resistance (Deformation Amplitude Index, DAI)

1 evidences

In 50 patients with bilateral progressive keratoconus, continuous and pulsed accelerated corneal collagen cross-linking with supplemental oxygen produced comparable improvements in corneal topography and biomechanics at one year.

Trust comment: Prospective randomized paired-eye study with 12-month follow-up and objective measures, though right/left-eye allocation and single-center design limit generalizability.

Study Details

PMID:38162570
Participants:50
Impact:P-KXL: 1.12→0.84 mm (p<0.01); C-KXL: 1.04→0.85 mm (p=0.03) at 1 year
Trust score:4/5

Endothelial cell count

1 evidences

In 50 patients with bilateral progressive keratoconus, continuous and pulsed accelerated corneal collagen cross-linking with supplemental oxygen produced comparable improvements in corneal topography and biomechanics at one year.

Trust comment: Prospective randomized paired-eye study with 12-month follow-up and objective measures, though right/left-eye allocation and single-center design limit generalizability.

Study Details

PMID:38162570
Participants:50
Impact:No significant change at 1 year
Trust score:4/5

P1NP (bone formation/procollagen I marker)

1 evidences

A single teriparatide injection caused short-term changes in calcium metabolism and biphasic changes in bone turnover markers; vitamin D metabolites (1,25(OH)2D) rose transiently but Vitamin D was not the intervention.

Trust comment: Randomized, double-blind, placebo-controlled pharmacodynamic study with complete follow-up but small sample size limits precision.

Study Details

PMID:23093347
Participants:30
Impact:Early −15% shortly after injection, then increase to ~+15% sustained up to 14 days
Trust score:4/5

Serum NTX / urinary CTX (bone resorption markers)

1 evidences

A single teriparatide injection caused short-term changes in calcium metabolism and biphasic changes in bone turnover markers; vitamin D metabolites (1,25(OH)2D) rose transiently but Vitamin D was not the intervention.

Trust comment: Randomized, double-blind, placebo-controlled pharmacodynamic study with complete follow-up but small sample size limits precision.

Study Details

PMID:23093347
Participants:30
Impact:Transient increase on day 1 followed by ~−10% decline persisting through 14 days
Trust score:4/5

Dermal fibrosis (histology/OCT)

1 evidences

In 50 volunteers with matched 5-mm wounds, autograft and decellularized dermis treatments yielded reduced dermal fibrosis and different remodeling compared with control and collagen-GAG scaffold over 28 days.

Trust comment: Prospective within-subject cohort with objective histologic and OCT validation in 50 volunteers, though short follow-up limits long-term scar assessment.

Study Details

PMID:26053202
Participants:50
Impact:Reduced scarring in autograft and DCD versus control and CG (Collagen-GAG); autograft minimal fibrosis (collagen I lower, p=0.047 and p=0.03)
Trust score:4/5

Collagen I levels

1 evidences

In 50 volunteers with matched 5-mm wounds, autograft and decellularized dermis treatments yielded reduced dermal fibrosis and different remodeling compared with control and collagen-GAG scaffold over 28 days.

Trust comment: Prospective within-subject cohort with objective histologic and OCT validation in 50 volunteers, though short follow-up limits long-term scar assessment.

Study Details

PMID:26053202
Participants:50
Impact:Lower in autograft-treated wounds (p=0.047 and p=0.03 compared to control)
Trust score:4/5

Regenerated dermis thickness

1 evidences

In 50 volunteers with matched 5-mm wounds, autograft and decellularized dermis treatments yielded reduced dermal fibrosis and different remodeling compared with control and collagen-GAG scaffold over 28 days.

Trust comment: Prospective within-subject cohort with objective histologic and OCT validation in 50 volunteers, though short follow-up limits long-term scar assessment.

Study Details

PMID:26053202
Participants:50
Impact:Thicker in DCD and autograft at 28 days versus control and CG (p=0.003 and p<0.0001)
Trust score:4/5

DKK1 / Sclerostin (Wnt inhibitors)

1 evidences

In 74 postmenopausal women, bisphosphonate therapy (clodronate or yearly zoledronate) reduced bone turnover markers and produced differential effects on Wnt inhibitors (transient DKK1 increases with zoledronate; delayed SOST increase with clodronate).

Trust comment: Data from participants in multicenter randomized placebo-controlled trials with standard biochemical endpoints, supporting credibility.

Study Details

PMID:25003812
Participants:74
Impact:ZOL: transient increase in DKK1 within 1 month (returns to baseline by 12 months); CLO: late increase in SOST at 12 months
Trust score:4/5

Synovial inflammatory cytokines (IL-6, IL-8, IL-10, TNF, IFNγ)

1 evidences

Analysis of 119 ACL-injured patients showed early ACL reconstruction prolonged elevated synovial inflammatory cytokines versus optional/delayed reconstruction over multiple timepoints, while collagen degradation markers did not differ between treatments over 5 years.

Trust comment: Nested analysis within a randomized trial with longitudinal biospecimens in 119 subjects; exploratory biomarker findings are plausible though heterogenous.

Study Details

PMID:28522220
Participants:119
Impact:Higher concentrations at various timepoints (e.g., IL-6, IL-8, IL-10, TNF at 4 months; IL-6 and TNF at 8 months; IFNγ at 5 years) with early reconstruction vs optional/delayed
Trust score:4/5

Cartilage/bone collagen degradation markers (ARGS-aggrecan, CTX-II, NTX-I)

1 evidences

Analysis of 119 ACL-injured patients showed early ACL reconstruction prolonged elevated synovial inflammatory cytokines versus optional/delayed reconstruction over multiple timepoints, while collagen degradation markers did not differ between treatments over 5 years.

Trust comment: Nested analysis within a randomized trial with longitudinal biospecimens in 119 subjects; exploratory biomarker findings are plausible though heterogenous.

Study Details

PMID:28522220
Participants:119
Impact:No differences between groups over 5 years
Trust score:4/5

Plaque index

1 evidences

Randomized comparative study (n=45; 3 groups of 15) testing periodontal dressings: collagen dressing showed greater symptomatic relief and improved clinical wound-healing indices versus light-cure and non-eugenol dressings.

Trust comment: Randomized study with 45 patients showing clinical benefit of collagen dressing, but limited sample size and incomplete reporting reduce strength of evidence.

Study Details

PMID:31797844
Participants:45
Impact:group I decreased from 1.48 ±0.56 to 1.18 ±0.40 (improvement)
Trust score:3/5

serum type I collagen N-telopeptide (NTx)

1 evidences

In renal transplant recipients, adding alendronate to calcium and calcitriol increased femoral neck BMD and decreased bone resorption marker NTx versus calcium+calcitriol alone in the short term.

Trust comment: Randomized clinical comparison but small sample and short-term follow-up limit generalizability.

Study Details

PMID:19100422
Participants:46
Impact:significant decrease (P < .05) with alendronate
Trust score:3/5

vertical distal papilla soft tissue change

1 evidences

RCT comparing immediate implants with or without DBBM-C (10% collagen); adding DBBM-C slightly reduced tissue dimensional changes with one significant benefit at the distal papilla.

Trust comment: Prospective randomized controlled clinical trial with complete 12-month follow-up but modest sample size (n=32).

Study Details

PMID:31815977
Participants:32
Impact:statistically significant improvement favoring DBBM-C (baseline to 12 months)
Trust score:4/5

cellulite and skin texture

1 evidences

Randomized double-blind vehicle-controlled 12-week trial of a topical firming/toning lotion (FTB) in 54 women showed significant improvements in skin firmness, texture, and cellulite and preclinical evidence of increased collagen and elastic fiber formation.

Trust comment: Randomized, double-blind, vehicle-controlled trial with objective instrumentation and preclinical histological/gene-expression support showing increases in collagen-related markers; moderate sample size.

Study Details

PMID:37683065
Participants:54
Impact:significant improvement vs baseline and vehicle at week 12
Trust score:4/5

collagen and elastic fiber formation (ex vivo)

1 evidences

Randomized double-blind vehicle-controlled 12-week trial of a topical firming/toning lotion (FTB) in 54 women showed significant improvements in skin firmness, texture, and cellulite and preclinical evidence of increased collagen and elastic fiber formation.

Trust comment: Randomized, double-blind, vehicle-controlled trial with objective instrumentation and preclinical histological/gene-expression support showing increases in collagen-related markers; moderate sample size.

Study Details

PMID:37683065
Participants:54
Impact:increased new collagen and elastic fibers; stimulated ECM renewal and gene expression
Trust score:4/5

glomerular filtration rate (Cr-51 GFR)

1 evidences

31 renal-allograft recipients randomized to cyclosporine reduction with or without rapamycin; rapamycin group had a fall in GFR and increases in collagen III expression and TIMP-2 without histological improvement in interstitial fibrosis.

Trust comment: Small randomized trial that directly measured collagen III expression and histological fibrosis; limited sample size and short follow-up reduce confidence but outcomes are directly collagen-related.

Study Details

PMID:12660500
Participants:31
Impact:decreased in rapamycin group from 31.6±8.9 to 27.3±8.6 mL/min (significant)
Trust score:3/5

interstitial fibrosis (Sirius red interstitial volume fraction)

1 evidences

31 renal-allograft recipients randomized to cyclosporine reduction with or without rapamycin; rapamycin group had a fall in GFR and increases in collagen III expression and TIMP-2 without histological improvement in interstitial fibrosis.

Trust comment: Small randomized trial that directly measured collagen III expression and histological fibrosis; limited sample size and short follow-up reduce confidence but outcomes are directly collagen-related.

Study Details

PMID:12660500
Participants:31
Impact:no decrease in rapamycin group (16.2→16.3%) vs control trend to decrease (15.3→11.2%)
Trust score:3/5

collagen content (vastus lateralis)

1 evidences

In human volunteers undergoing 35–90 days of simulated microgravity with or without resistance exercise, quadriceps muscle volume changed but major contractile and connective proteins in the vastus lateralis (including collagen) were preserved.

Trust comment: Human intervention studies with biopsy outcomes and countermeasures provide direct measures but group sizes are small, limiting precision.

Study Details

PMID:17670860
Participants:38
Impact:no change (P>0.05)
Trust score:4/5

quadriceps femoris muscle volume

1 evidences

In human volunteers undergoing 35–90 days of simulated microgravity with or without resistance exercise, quadriceps muscle volume changed but major contractile and connective proteins in the vastus lateralis (including collagen) were preserved.

Trust comment: Human intervention studies with biopsy outcomes and countermeasures provide direct measures but group sizes are small, limiting precision.

Study Details

PMID:17670860
Participants:38
Impact:35d ULLS -9%; 35d ULLS+RE +8%; 90d BR -18%; 90d BR+RE -1%
Trust score:4/5

soleus mixed and myofibrillar protein

1 evidences

In human volunteers undergoing 35–90 days of simulated microgravity with or without resistance exercise, quadriceps muscle volume changed but major contractile and connective proteins in the vastus lateralis (including collagen) were preserved.

Trust comment: Human intervention studies with biopsy outcomes and countermeasures provide direct measures but group sizes are small, limiting precision.

Study Details

PMID:17670860
Participants:38
Impact:mixed -12% (35d ULLS and 90d BR); myofibrillar -12% (35d ULLS) and -8% (90d BR)
Trust score:4/5

platelet aggregation (ADP/collagen/PAF in vitro)

1 evidences

In vitro and two randomized healthy-volunteer trials showed near-complete Lp-PLA2 inhibition but no clinically relevant enhancement of platelet aggregation to collagen, ADP, or PAF.

Trust comment: Well-powered, randomized double-blind clinical trials with objective aggregation assays and consistent in vitro corroboration.

Study Details

PMID:24475026
Participants:87
Impact:no demonstrable effect (p>0.05)
Trust score:5/5

Lp-PLA2 activity

1 evidences

In vitro and two randomized healthy-volunteer trials showed near-complete Lp-PLA2 inhibition but no clinically relevant enhancement of platelet aggregation to collagen, ADP, or PAF.

Trust comment: Well-powered, randomized double-blind clinical trials with objective aggregation assays and consistent in vitro corroboration.

Study Details

PMID:24475026
Participants:87
Impact:~90% inhibition at several timepoints (e.g., 89.9%–96.6%)
Trust score:5/5

collagen-induced whole blood platelet aggregation

1 evidences

In cardiac reoperations, harvesting and reinfusing autologous platelet concentrate reduced bleeding and increased platelet counts and collagen-induced whole blood platelet aggregation compared with autologous whole blood.

Trust comment: Controlled clinical comparison in surgical patients with clear haemostatic endpoints, but single-center and modest size reduce external validity.

Study Details

PMID:11454260
Participants:48
Impact:increased significantly after reinfusion in platelet-concentrate group versus whole-blood group
Trust score:3/5

mediastinal drainage (12 h)

1 evidences

In cardiac reoperations, harvesting and reinfusing autologous platelet concentrate reduced bleeding and increased platelet counts and collagen-induced whole blood platelet aggregation compared with autologous whole blood.

Trust comment: Controlled clinical comparison in surgical patients with clear haemostatic endpoints, but single-center and modest size reduce external validity.

Study Details

PMID:11454260
Participants:48
Impact:Group PC 435 ± 273 ml vs Group WB 909 ± 209 ml (P < 0.001)
Trust score:3/5

platelet count after reinfusion

1 evidences

In cardiac reoperations, harvesting and reinfusing autologous platelet concentrate reduced bleeding and increased platelet counts and collagen-induced whole blood platelet aggregation compared with autologous whole blood.

Trust comment: Controlled clinical comparison in surgical patients with clear haemostatic endpoints, but single-center and modest size reduce external validity.

Study Details

PMID:11454260
Participants:48
Impact:increased (significant vs WB)
Trust score:3/5

aminoterminal propeptide of type I procollagen

1 evidences

In postmenopausal breast cancer patients, tamoxifen reduced markers of bone resorption and formation and increased spine and femoral BMD, whereas toremifene showed smaller effects.

Trust comment: Randomized comparison with biochemical and BMD endpoints in 30 patients; moderate size but measured biomarkers and BMD are standard outcomes.

Study Details

PMID:9543133
Participants:30
Impact:tamoxifen decreased by ~22%
Trust score:4/5

collagen deposition (nasal polyps)

1 evidences

In a 14-day randomized trial, transnasal budesonide reduced polyp size and eosinophilic inflammation but increased collagen deposition and TIMP levels in nasal polyps versus placebo.

Trust comment: Randomized double-blind trial with histologic and immunologic endpoints in 60 patients; outcomes and assays appropriate though short duration.

Study Details

PMID:25483598
Participants:60
Impact:increased significantly with budesonide versus placebo
Trust score:4/5

polyp size (Kennedy score)

1 evidences

In a 14-day randomized trial, transnasal budesonide reduced polyp size and eosinophilic inflammation but increased collagen deposition and TIMP levels in nasal polyps versus placebo.

Trust comment: Randomized double-blind trial with histologic and immunologic endpoints in 60 patients; outcomes and assays appropriate though short duration.

Study Details

PMID:25483598
Participants:60
Impact:reduced vs placebo; mean difference -0.73 units (95% CI -1.15 to -0.32; P = .002)
Trust score:4/5

TIMP levels

1 evidences

In a 14-day randomized trial, transnasal budesonide reduced polyp size and eosinophilic inflammation but increased collagen deposition and TIMP levels in nasal polyps versus placebo.

Trust comment: Randomized double-blind trial with histologic and immunologic endpoints in 60 patients; outcomes and assays appropriate though short duration.

Study Details

PMID:25483598
Participants:60
Impact:TIMP-1, TIMP-2, TIMP-4 increased (significant)
Trust score:4/5

Horizontal ridge width at 1 mm (HW-1)

1 evidences

DBBM with 10% collagen (DBBM-C) was non-inferior to DBBM alone for maintaining alveolar ridge width 4 months after extraction.

Trust comment: Randomized non-inferiority RCT with objective CBCT endpoints but modest sample size and short (4-month) follow-up.

Study Details

PMID:30710389
Participants:66
Impact:DBBM-C: -1.60 mm vs DBBM: -1.37 mm (difference 0.23 mm; p=0.28; non-inferior)
Trust score:4/5

Horizontal ridge width at 3 mm (HW-3)

1 evidences

DBBM with 10% collagen (DBBM-C) was non-inferior to DBBM alone for maintaining alveolar ridge width 4 months after extraction.

Trust comment: Randomized non-inferiority RCT with objective CBCT endpoints but modest sample size and short (4-month) follow-up.

Study Details

PMID:30710389
Participants:66
Impact:DBBM-C: -0.98 mm vs DBBM: -0.84 mm (p=0.40; non-inferior)
Trust score:4/5

Horizontal ridge width at 5 mm (HW-5)

1 evidences

DBBM with 10% collagen (DBBM-C) was non-inferior to DBBM alone for maintaining alveolar ridge width 4 months after extraction.

Trust comment: Randomized non-inferiority RCT with objective CBCT endpoints but modest sample size and short (4-month) follow-up.

Study Details

PMID:30710389
Participants:66
Impact:DBBM-C: -0.67 mm vs DBBM: -0.56 mm (p=0.36; non-inferior)
Trust score:4/5

VAS pain score

1 evidences

Injection of autologous skin-derived collagen-producing fibroblasts improved pain and function in refractory Achilles tendinosis at six months.

Trust comment: Randomized double-blind human study but small sample and short follow-up; intervention is cell therapy (collagen-producing cells), not oral collagen supplement.

Study Details

PMID:22241604
Participants:32
Impact:decrease (significant at 6 months, p<0.001)
Trust score:3/5

pro-collagen type III N-terminal peptide (PIIINP)

1 evidences

In mild-moderate heart failure, spironolactone lowered BNP and a blood marker of collagen turnover (PIIINP) but worsened renal function and self-reported quality of life over 3 months.

Trust comment: Randomized, double-blind trial measuring a collagen turnover marker (PIIINP) with significant changes, but small sample and short duration limit generalizability.

Study Details

PMID:17126073
Participants:40
Impact:decreased by 0.6 µmol/L in spironolactone group vs +0.02 µmol/L in placebo (P=0.02)
Trust score:3/5

creatinine

1 evidences

In mild-moderate heart failure, spironolactone lowered BNP and a blood marker of collagen turnover (PIIINP) but worsened renal function and self-reported quality of life over 3 months.

Trust comment: Randomized, double-blind trial measuring a collagen turnover marker (PIIINP) with significant changes, but small sample and short duration limit generalizability.

Study Details

PMID:17126073
Participants:40
Impact:increased by 10.7 µmol/L in spironolactone group vs -0.3 µmol/L in placebo (P=0.01)
Trust score:3/5

urinary C-terminal telopeptide of type I collagen (u-CTX)

1 evidences

ONO-5334 produced dose-dependent, large reductions in a bone collagen resorption marker (urinary C-terminal telopeptide of type I collagen) with minimal effects on bone-formation markers.

Trust comment: Well-conducted phase 1 multiple-dose study in 120 postmenopausal women showing robust, dose-dependent suppression of bone collagen resorption markers, but endpoints are biochemical and short-term.

Study Details

PMID:21719717
Participants:120
Impact:reduced by 44.9% ±13.6% (100 mg), 84.5% ±4.4% (300 mg), 92.5% ±1.3% (600 mg) at 15-day cohorts
Trust score:4/5

bone formation markers (B-ALP, osteocalcin)

1 evidences

ONO-5334 produced dose-dependent, large reductions in a bone collagen resorption marker (urinary C-terminal telopeptide of type I collagen) with minimal effects on bone-formation markers.

Trust comment: Well-conducted phase 1 multiple-dose study in 120 postmenopausal women showing robust, dose-dependent suppression of bone collagen resorption markers, but endpoints are biochemical and short-term.

Study Details

PMID:21719717
Participants:120
Impact:far smaller or no appreciable changes after 28 days
Trust score:4/5

TRAP5b (osteoclast number marker)

1 evidences

ONO-5334 produced dose-dependent, large reductions in a bone collagen resorption marker (urinary C-terminal telopeptide of type I collagen) with minimal effects on bone-formation markers.

Trust comment: Well-conducted phase 1 multiple-dose study in 120 postmenopausal women showing robust, dose-dependent suppression of bone collagen resorption markers, but endpoints are biochemical and short-term.

Study Details

PMID:21719717
Participants:120
Impact:no appreciable change after multiple dosing
Trust score:4/5

operative time

2 evidences

Randomized trial comparing LigaSure (creates a collagen seal) versus conventional clips/ties in thyroidectomy; no change in operative time, improved postoperative VHI with LigaSure, but substantially higher device cost.

Trust comment: Small randomized trial with objective and subjective outcomes but limited power due to small sample size.

Study Details

PMID:20643002
Participants:28
Impact:no significant change (68.6 vs 68.5 minutes)
Trust score:3/5

Using rhBMP-2 on an absorbable collagen sponge with interbody cages yielded higher fusion rates and less operative time and blood loss than autograft, avoiding donor-site morbidity.

Trust comment: Prospective randomized multicenter trial with objective radiographic endpoints; however collagen was used as a carrier for rhBMP-2, so effects cannot be attributed solely to collagen.

Study Details

PMID:12394656
Participants:279
Impact:reduced by 0.4 hours (1.6 vs 2.0 h)
Trust score:4/5

plasma salmon calcitonin Cmax

1 evidences

In healthy postmenopausal women (three dosing cohorts totaling 81), a single 0.8 mg oral salmon calcitonin dose significantly suppressed serum CTX (a collagen type I degradation marker), with pre-dinner dosing producing the largest overall suppression.

Trust comment: Well-designed randomized double-blind crossover PK/PD human study with objective biomarker (CTX) measures, though authors have declared company affiliations.

Study Details

PMID:19055791
Participants:81
Impact:Morning/pre-dinner Cmax ≈45 pg/ml; evening Cmax ≈23.8 pg/ml (evening lower, p≈0.05 for morning vs evening)
Trust score:4/5

serum CTX (bone resorption; collagen I degradation) nadir

1 evidences

In healthy postmenopausal women (three dosing cohorts totaling 81), a single 0.8 mg oral salmon calcitonin dose significantly suppressed serum CTX (a collagen type I degradation marker), with pre-dinner dosing producing the largest overall suppression.

Trust comment: Well-designed randomized double-blind crossover PK/PD human study with objective biomarker (CTX) measures, though authors have declared company affiliations.

Study Details

PMID:19055791
Participants:81
Impact:Serum CTX fell to ~22% of pre-dose at nadir (~78% reduction); maximum difference vs placebo 40–50% (morning) and ≈75% (pre-dinner/evening) at 1–3 h post-dose
Trust score:4/5

placebo-corrected AUC0–24 of serum CTX (overall suppression)

1 evidences

In healthy postmenopausal women (three dosing cohorts totaling 81), a single 0.8 mg oral salmon calcitonin dose significantly suppressed serum CTX (a collagen type I degradation marker), with pre-dinner dosing producing the largest overall suppression.

Trust comment: Well-designed randomized double-blind crossover PK/PD human study with objective biomarker (CTX) measures, though authors have declared company affiliations.

Study Details

PMID:19055791
Participants:81
Impact:Morning: −232 (%×hrs) ≈10% overall suppression; Pre-dinner: −603 (%×hrs) ≈25% overall suppression; Evening: −538 (%×hrs) (trend, p=0.06)
Trust score:4/5

scar appearance

1 evidences

Plasma gel injections, alone or combined with microneedling, improved atrophic acne scars and increased collagen and elastic fiber formation on histology.

Trust comment: Randomized single-blind trial with 60 patients and histological endpoints; moderate-to-good quality.

Study Details

PMID:32108322
Participants:60
Impact:improved (statistically significant)
Trust score:4/5

new collagen formation

1 evidences

Plasma gel injections, alone or combined with microneedling, improved atrophic acne scars and increased collagen and elastic fiber formation on histology.

Trust comment: Randomized single-blind trial with 60 patients and histological endpoints; moderate-to-good quality.

Study Details

PMID:32108322
Participants:60
Impact:increased (histology)
Trust score:4/5

elastic fiber organization

1 evidences

Plasma gel injections, alone or combined with microneedling, improved atrophic acne scars and increased collagen and elastic fiber formation on histology.

Trust comment: Randomized single-blind trial with 60 patients and histological endpoints; moderate-to-good quality.

Study Details

PMID:32108322
Participants:60
Impact:increased and more organized (histology)
Trust score:4/5

scar outcome scores

1 evidences

A multimodal scar prevention program (including occlusive tape with active agents targeting hydration, inflammation, and collagen maturation) improved scar outcomes at 6 months across treated groups.

Trust comment: Multiple patient groups with some historical controls and non-randomized comparisons; results positive but potential bias and heterogeneity.

Study Details

PMID:19048338
Participants:120
Impact:improved (statistically significant at 6 months)
Trust score:3/5

patient and observer assessments

1 evidences

A multimodal scar prevention program (including occlusive tape with active agents targeting hydration, inflammation, and collagen maturation) improved scar outcomes at 6 months across treated groups.

Trust comment: Multiple patient groups with some historical controls and non-randomized comparisons; results positive but potential bias and heterogeneity.

Study Details

PMID:19048338
Participants:120
Impact:both showed correlated improvement
Trust score:3/5

targeted collagen maturation

1 evidences

A multimodal scar prevention program (including occlusive tape with active agents targeting hydration, inflammation, and collagen maturation) improved scar outcomes at 6 months across treated groups.

Trust comment: Multiple patient groups with some historical controls and non-randomized comparisons; results positive but potential bias and heterogeneity.

Study Details

PMID:19048338
Participants:120
Impact:reported improvement in scar morphology (qualitative/histologic aims)
Trust score:3/5

reactive oxygen species

1 evidences

In 200 CRF patients randomized to autologous MSCs vs N-acetylcysteine, MSCs produced greater improvements in renal function markers and oxidative stress over 8 weeks.

Trust comment: Randomized study with 200 patients and multiple biochemical endpoints; good sample size though described as a pilot and limited to 8-week follow-up.

Study Details

PMID:34602393
Participants:200
Impact:decreased more with MSCs (statistically significant)
Trust score:4/5

horizontal buccal crest dimensional change

1 evidences

In 86 immediate-implant sites, placing DBBM-C (contains 10% collagen) in the implant-bone gap reduced horizontal buccal bone loss at 16 weeks compared with no graft.

Trust comment: Randomized clinical trial with 86 sites and direct objective bone measurements; intervention contains collagen (DBBM-C) so findings are relevant though effect is from a composite graft product.

Study Details

PMID:27273298
Participants:86
Impact:mean reduction 1.1 mm (29%) test (DBBM-C) vs 1.6 mm (38%) control; difference ≈0.5 mm (p=0.02)
Trust score:4/5

vertical/horizontal crestal bone change (anterior maxilla/thin buccal plates)

1 evidences

In 86 immediate-implant sites, placing DBBM-C (contains 10% collagen) in the implant-bone gap reduced horizontal buccal bone loss at 16 weeks compared with no graft.

Trust comment: Randomized clinical trial with 86 sites and direct objective bone measurements; intervention contains collagen (DBBM-C) so findings are relevant though effect is from a composite graft product.

Study Details

PMID:27273298
Participants:86
Impact:greater preservation at anterior sites and thin buccal plates (statistically significant subgroup effects)
Trust score:4/5

RBC count loss

1 evidences

Use of a collagen-containing hemostatic sealant (TachoSil) at the staple line reduced postoperative blood loss compared with no sealant.

Trust comment: Prospective, randomized, single-blind trial (n=30) showing clinically relevant haemostatic effects of a collagen-containing product; small sample and preliminary.

Study Details

PMID:22691828
Participants:30
Impact:smaller decrease with TachoSil: −0.4×10^6/mL vs −1.7×10^6/mL
Trust score:3/5

Hemoglobin (Hb) decrease

1 evidences

Use of a collagen-containing hemostatic sealant (TachoSil) at the staple line reduced postoperative blood loss compared with no sealant.

Trust comment: Prospective, randomized, single-blind trial (n=30) showing clinically relevant haemostatic effects of a collagen-containing product; small sample and preliminary.

Study Details

PMID:22691828
Participants:30
Impact:smaller decrease with TachoSil: −0.5 g/dL vs −1.2 g/dL
Trust score:3/5

postoperative drainage fluid

1 evidences

Use of a collagen-containing hemostatic sealant (TachoSil) at the staple line reduced postoperative blood loss compared with no sealant.

Trust comment: Prospective, randomized, single-blind trial (n=30) showing clinically relevant haemostatic effects of a collagen-containing product; small sample and preliminary.

Study Details

PMID:22691828
Participants:30
Impact:absent/minimal with TachoSil vs 120/80/60 mL on POD1–3 without
Trust score:3/5

biomaterial volume (MatV/TV)

1 evidences

Both techniques (non-resorbable membrane vs titanium mesh + collagen membrane) produced ~30% newly formed bone by micro-CT with no significant differences between groups.

Trust comment: Randomized human study (n=40) with objective micro-CT endpoints; moderate quality but limited sample for subgroup inference about collagen membrane specifics.

Study Details

PMID:34006069
Participants:40
Impact:8.9% (group A) vs 11.0% (group B); no significant difference
Trust score:3/5

soft tissue volume (StV/TV)

1 evidences

Both techniques (non-resorbable membrane vs titanium mesh + collagen membrane) produced ~30% newly formed bone by micro-CT with no significant differences between groups.

Trust comment: Randomized human study (n=40) with objective micro-CT endpoints; moderate quality but limited sample for subgroup inference about collagen membrane specifics.

Study Details

PMID:34006069
Participants:40
Impact:62.4% (group A) vs 59.0% (group B); no significant difference
Trust score:3/5

MMP-1 expression

1 evidences

Eight weeks of split-face home device use improved skin-aging measures and increased type I collagen expression while decreasing MMP-1, with no adverse effects.

Trust comment: Randomized split-face clinical trial with supportive ex vivo and histology data, moderate sample size and objective endpoints.

Study Details

PMID:38236440
Participants:36
Impact:decreased after 8 weeks
Trust score:4/5

use of IOP-lowering medications

1 evidences

In 33 children, adding Ologen (a collagen matrix) to Ahmed valve implantation lowered intraocular pressure more than valve alone over follow-up without added safety issues.

Trust comment: Prospective randomized split (33 eyes) with good follow-up; small sample limits precision but design is strong and Ologen is a collagen matrix.

Study Details

PMID:36100118
Participants:33
Impact:decreased (significant)
Trust score:4/5

surgical success probability

1 evidences

In 33 children, adding Ologen (a collagen matrix) to Ahmed valve implantation lowered intraocular pressure more than valve alone over follow-up without added safety issues.

Trust comment: Prospective randomized split (33 eyes) with good follow-up; small sample limits precision but design is strong and Ologen is a collagen matrix.

Study Details

PMID:36100118
Participants:33
Impact:77% vs 63% at 24 months (difference not statistically significant)
Trust score:4/5

skin tone (ITA°)

1 evidences

Two single-center 28-day topical lotion studies (5% and 20% TBFE) in adults showed improved skin tone, reduced water loss, increased hydration and reduced wrinkles.

Trust comment: Human data from two small, single-center open pre–post studies (n=60 total) with objective measures but limited power and no placebo control.

Study Details

PMID:39161108
Participants:60
Impact:+5% (5% lotion) and +8% (20% lotion) at Day 28
Trust score:3/5

trans-epidermal water loss (TEWL)

1 evidences

Two single-center 28-day topical lotion studies (5% and 20% TBFE) in adults showed improved skin tone, reduced water loss, increased hydration and reduced wrinkles.

Trust comment: Human data from two small, single-center open pre–post studies (n=60 total) with objective measures but limited power and no placebo control.

Study Details

PMID:39161108
Participants:60
Impact:-20% (5% lotion) and -23% (20% lotion) at Day 28
Trust score:3/5

dry eye symptoms (OSDI)

1 evidences

Randomized trial (n=126) testing dissolvable punctal plugs after intravitreal injection prep with PVI found no overall reduction in ocular surface symptoms, but benefit in subgroup with objective dry eye.

Trust comment: Moderately sized randomized trial (n=126) directly testing a collagen-based device with clear endpoints; subgroup effects limit generalizability.

Study Details

PMID:33746207
Participants:126
Impact:no significant overall reduction (p=0.137)
Trust score:4/5

dry eye symptoms (SPEED II)

1 evidences

Randomized trial (n=126) testing dissolvable punctal plugs after intravitreal injection prep with PVI found no overall reduction in ocular surface symptoms, but benefit in subgroup with objective dry eye.

Trust comment: Moderately sized randomized trial (n=126) directly testing a collagen-based device with clear endpoints; subgroup effects limit generalizability.

Study Details

PMID:33746207
Participants:126
Impact:no significant overall reduction (p=0.381)
Trust score:4/5

subgroup with objective dry eye

1 evidences

Randomized trial (n=126) testing dissolvable punctal plugs after intravitreal injection prep with PVI found no overall reduction in ocular surface symptoms, but benefit in subgroup with objective dry eye.

Trust comment: Moderately sized randomized trial (n=126) directly testing a collagen-based device with clear endpoints; subgroup effects limit generalizability.

Study Details

PMID:33746207
Participants:126
Impact:significant symptom improvement with CPP (p=0.046)
Trust score:4/5

lateral bone thickness (LBT) change

1 evidences

In 64 patients, equine-derived collagenated xenogeneic bone blocks were non-inferior to autogenous bone blocks for horizontal ridge augmentation, with less early post-op pain.

Trust comment: Randomized non-inferiority clinical trial with objective radiographic endpoints and clinical outcomes; moderate sample size.

Study Details

PMID:35833539
Participants:64
Impact:median +2.90 mm (CXBB) vs +3.00 mm (ABB) at 30 weeks
Trust score:4/5

early implant failure rate

1 evidences

In 64 patients, equine-derived collagenated xenogeneic bone blocks were non-inferior to autogenous bone blocks for horizontal ridge augmentation, with less early post-op pain.

Trust comment: Randomized non-inferiority clinical trial with objective radiographic endpoints and clinical outcomes; moderate sample size.

Study Details

PMID:35833539
Participants:64
Impact:20% (CXBB) vs 10% (ABB); no significant difference
Trust score:4/5

serum β-C-terminal telopeptides of type I collagen (β-CTx)

1 evidences

In 833 glucocorticoid-treated patients, annual zoledronic acid reduced bone turnover markers more than daily risedronate over 12 months.

Trust comment: Large randomized study with clear biochemical endpoints and appropriate stratification; results robust for bone turnover markers.

Study Details

PMID:23365149
Participants:833
Impact:greater reductions with zoledronic acid vs risedronate (P < 0.05 at most time points; significant at 12 months)
Trust score:4/5

urine N-telopeptides of type I collagen (NTx)

1 evidences

In 833 glucocorticoid-treated patients, annual zoledronic acid reduced bone turnover markers more than daily risedronate over 12 months.

Trust comment: Large randomized study with clear biochemical endpoints and appropriate stratification; results robust for bone turnover markers.

Study Details

PMID:23365149
Participants:833
Impact:greater reductions with zoledronic acid vs risedronate (P < 0.05)
Trust score:4/5

Bone mineral density (areal and volumetric)

1 evidences

PTH therapy increased early collagen-formation markers and larger short-term increases predicted greater spine and hip BMD gains at 1 year.

Trust comment: Large randomized placebo-controlled multicenter trial with objective BMD measures; measures PINP (a collagen formation marker) indirectly related to collagen biology.

Study Details

PMID:16449339
Participants:238
Impact:increased at 1 year (greater increases associated with larger short-term turnover increases)
Trust score:4/5

skin texture and atrophy improvement

1 evidences

Single-session split-face trial found both lasers improved acne scar appearance and increased dermal collagen/elastic fibers by 3 months, with fewer PIH events on picosecond side.

Trust comment: Randomized split-face trial with histologic and imaging endpoints but small sample (n=25).

Study Details

PMID:32910030
Participants:25
Impact:significant improvement (physician scores); no difference between FxPico and FxCO2
Trust score:4/5

collagen and elastic fiber increase

1 evidences

Single-session split-face trial found both lasers improved acne scar appearance and increased dermal collagen/elastic fibers by 3 months, with fewer PIH events on picosecond side.

Trust comment: Randomized split-face trial with histologic and imaging endpoints but small sample (n=25).

Study Details

PMID:32910030
Participants:25
Impact:increased at 3 months on histology
Trust score:4/5

scar height (VSS)

1 evidences

Randomized paired trial comparing intralesional verapamil (a calcium-channel blocker) versus triamcinolone for keloids; steroids improved scars, verapamil showed no significant benefit.

Trust comment: Randomized paired-design trial with 50 patients using validated VSS scale, but follow-up limited to 3 months and lesion-level reporting.

Study Details

PMID:29886113
Participants:50
Impact:reduced to zero with triamcinolone by week 15
Trust score:4/5

scar pliability (VSS)

1 evidences

Randomized paired trial comparing intralesional verapamil (a calcium-channel blocker) versus triamcinolone for keloids; steroids improved scars, verapamil showed no significant benefit.

Trust comment: Randomized paired-design trial with 50 patients using validated VSS scale, but follow-up limited to 3 months and lesion-level reporting.

Study Details

PMID:29886113
Participants:50
Impact:reduced to zero with triamcinolone by week 15
Trust score:4/5

verapamil efficacy

1 evidences

Randomized paired trial comparing intralesional verapamil (a calcium-channel blocker) versus triamcinolone for keloids; steroids improved scars, verapamil showed no significant benefit.

Trust comment: Randomized paired-design trial with 50 patients using validated VSS scale, but follow-up limited to 3 months and lesion-level reporting.

Study Details

PMID:29886113
Participants:50
Impact:no significant improvement vs baseline
Trust score:4/5

adipocyte-regeneration gene expression

1 evidences

Injections for nasolabial folds showed PLLA (not CaHA) upregulated adipocyte-regeneration genes, suggesting a unique adipocyte-mediated regenerative signature absent with calcium hydroxylapatite.

Trust comment: Randomized molecular endpoint study with biopsies and RNA-seq but small sample and indirect clinical endpoints.

Study Details

PMID:39480040
Participants:21
Impact:PLLA upregulated adipocyte-related/regenerative genes (significant differences at Day 90 for ~9–12 genes, p<0.05)
Trust score:3/5

distinct gene-regulation signature

1 evidences

Injections for nasolabial folds showed PLLA (not CaHA) upregulated adipocyte-regeneration genes, suggesting a unique adipocyte-mediated regenerative signature absent with calcium hydroxylapatite.

Trust comment: Randomized molecular endpoint study with biopsies and RNA-seq but small sample and indirect clinical endpoints.

Study Details

PMID:39480040
Participants:21
Impact:PLLA and CaHA showed differing gene expression patterns at Day 90
Trust score:3/5

clinical implication (collagen-related)

1 evidences

Injections for nasolabial folds showed PLLA (not CaHA) upregulated adipocyte-regeneration genes, suggesting a unique adipocyte-mediated regenerative signature absent with calcium hydroxylapatite.

Trust comment: Randomized molecular endpoint study with biopsies and RNA-seq but small sample and indirect clinical endpoints.

Study Details

PMID:39480040
Participants:21
Impact:PLLA signature suggests effects beyond collagen structure (hypothesized longer-lasting/regenerative effect)
Trust score:3/5

flexibility

1 evidences

In 52 postmenopausal osteoporotic women on alendronate, twice-weekly WBV improved flexibility, balance, and walking speed, while collagen turnover markers changed similarly in both groups.

Trust comment: Randomized controlled trial with objective functional endpoints and biochemical markers, moderate sample size (n=52).

Study Details

PMID:22947545
Participants:52
Impact:significant improvement in exercise group vs control after 6 months
Trust score:4/5

body balance and walking velocity

1 evidences

In 52 postmenopausal osteoporotic women on alendronate, twice-weekly WBV improved flexibility, balance, and walking speed, while collagen turnover markers changed similarly in both groups.

Trust comment: Randomized controlled trial with objective functional endpoints and biochemical markers, moderate sample size (n=52).

Study Details

PMID:22947545
Participants:52
Impact:significant improvement in exercise group vs control after 6 months
Trust score:4/5

urinary N-terminal telopeptides of type I collagen

1 evidences

In 52 postmenopausal osteoporotic women on alendronate, twice-weekly WBV improved flexibility, balance, and walking speed, while collagen turnover markers changed similarly in both groups.

Trust comment: Randomized controlled trial with objective functional endpoints and biochemical markers, moderate sample size (n=52).

Study Details

PMID:22947545
Participants:52
Impact:reductions comparable between groups (no between-group difference)
Trust score:4/5

subject-assessed ≥1-point NLF improvement

1 evidences

In 372 adults, autologous fibroblast injections significantly improved nasolabial fold wrinkles versus placebo with mostly mild adverse events.

Trust comment: Large multicenter double-blind placebo-controlled RCT with validated scales and robust sample size (n=372).

Study Details

PMID:22409385
Participants:372
Impact:78% with autologous fibroblast vs 48% placebo achieved ≥1-point improvement at 6 months (p<0.001)
Trust score:5/5

evaluator-assessed ≥1-point NLF improvement

1 evidences

In 372 adults, autologous fibroblast injections significantly improved nasolabial fold wrinkles versus placebo with mostly mild adverse events.

Trust comment: Large multicenter double-blind placebo-controlled RCT with validated scales and robust sample size (n=372).

Study Details

PMID:22409385
Participants:372
Impact:64% vs 36% (p<0.001)
Trust score:5/5

complete ulcer healing (proportion)

1 evidences

Randomized trial: topical recombinant human EGF accelerated healing of diabetic foot ulcers, with greater collagen/fibroblast development in treated wounds.

Trust comment: Randomized controlled trial with clear clinical and histologic outcomes but small sample size; results appear robust for the measured endpoints.

Study Details

PMID:31878810
Participants:50
Impact:78% (Regen-D 150, n=27) vs 52% (placebo, n=23)
Trust score:4/5

collagen and fibroblast development in wound

1 evidences

Randomized trial: topical recombinant human EGF accelerated healing of diabetic foot ulcers, with greater collagen/fibroblast development in treated wounds.

Trust comment: Randomized controlled trial with clear clinical and histologic outcomes but small sample size; results appear robust for the measured endpoints.

Study Details

PMID:31878810
Participants:50
Impact:significantly increased in treatment group (qualitative histologic/biochemical finding)
Trust score:4/5

Inflammatory cell infiltration (macrophages, T cells, HLA-DR+)

1 evidences

Simvastatin reduced plaque inflammation and MMP activity and increased plaque collagen content, consistent with plaque stabilization.

Trust comment: Randomized pre-surgical intervention with clear, highly significant tissue-level changes supports reliability though single-center pathology measures limit generalizability.

Study Details

PMID:12654603
Participants:70
Impact:decreased (P<0.0001)
Trust score:4/5

MMP expression/activity

1 evidences

Simvastatin reduced plaque inflammation and MMP activity and increased plaque collagen content, consistent with plaque stabilization.

Trust comment: Randomized pre-surgical intervention with clear, highly significant tissue-level changes supports reliability though single-center pathology measures limit generalizability.

Study Details

PMID:12654603
Participants:70
Impact:decreased (P<0.0001)
Trust score:4/5

Epinephrine-induced aggregation

1 evidences

Adding clopidogrel to aspirin significantly reduced multiple measures of platelet activation versus aspirin alone in heart failure patients with heightened platelet activity.

Trust comment: Randomized trial with clear between-group differences on multiple platelet function assays, though modest sample size.

Study Details

PMID:14564328
Participants:50
Impact:decreased (P = .0016)
Trust score:4/5

Collagen-induced aggregation

1 evidences

Adding clopidogrel to aspirin significantly reduced multiple measures of platelet activation versus aspirin alone in heart failure patients with heightened platelet activity.

Trust comment: Randomized trial with clear between-group differences on multiple platelet function assays, though modest sample size.

Study Details

PMID:14564328
Participants:50
Impact:no change
Trust score:4/5

Bone maturation rate

1 evidences

Three years of combined GH and GnRHa slowed bone maturation and increased predicted adult height, while collagen propeptide markers did not change.

Trust comment: Randomized controlled design with clear clinical endpoints but small sample limits precision of biochemical endpoints.

Study Details

PMID:11443153
Participants:36
Impact:decreased (0.55 vs 1.15 yr/yr treated vs controls)
Trust score:4/5

Predicted adult height gain

1 evidences

Three years of combined GH and GnRHa slowed bone maturation and increased predicted adult height, while collagen propeptide markers did not change.

Trust comment: Randomized controlled design with clear clinical endpoints but small sample limits precision of biochemical endpoints.

Study Details

PMID:11443153
Participants:36
Impact:+8.0 cm (girls) / +10.4 cm (boys) compared with controls
Trust score:4/5

Collagen propeptides (type I and III)

1 evidences

Three years of combined GH and GnRHa slowed bone maturation and increased predicted adult height, while collagen propeptide markers did not change.

Trust comment: Randomized controlled design with clear clinical endpoints but small sample limits precision of biochemical endpoints.

Study Details

PMID:11443153
Participants:36
Impact:no change
Trust score:4/5

TXB2 (thromboxane) production

1 evidences

Indobufen and aspirin similarly suppressed thromboxane production and platelet aggregation but indobufen spared prostacyclin production relative to aspirin.

Trust comment: Small, randomized crossover and single-dose substudy with consistent pharmacodynamic differences but limited sample size.

Study Details

PMID:8701417
Participants:25
Impact:similarly inhibited (~97–98% single dose; near-complete after 7 days)
Trust score:3/5

6-keto-PGF1α (prostacyclin index)

1 evidences

Indobufen and aspirin similarly suppressed thromboxane production and platelet aggregation but indobufen spared prostacyclin production relative to aspirin.

Trust comment: Small, randomized crossover and single-dose substudy with consistent pharmacodynamic differences but limited sample size.

Study Details

PMID:8701417
Participants:25
Impact:less inhibited by indobufen vs aspirin (single dose: 81% vs >98%; 7 days: 20% vs 91%)
Trust score:3/5

Whole blood platelet aggregation

1 evidences

Indobufen and aspirin similarly suppressed thromboxane production and platelet aggregation but indobufen spared prostacyclin production relative to aspirin.

Trust comment: Small, randomized crossover and single-dose substudy with consistent pharmacodynamic differences but limited sample size.

Study Details

PMID:8701417
Participants:25
Impact:similarly inhibited after 7 days (both drugs)
Trust score:3/5

2-h urinary hydroxyproline excretion

1 evidences

Low-dose cyclical gallium nitrate reduced serum alkaline phosphatase and urinary markers of collagen turnover at higher doses in Paget's disease.

Trust comment: Pilot multicenter trial with clear dose-response biochemical effects but limited duration and heterogeneous prior therapies in participants.

Study Details

PMID:7852526
Participants:49
Impact:+9% (0.05 mg/kg) / -10% (0.25 mg/kg) / -17% (0.5 mg/kg); nadir at 10 weeks
Trust score:3/5

Urinary N-telopeptide collagen cross-links

1 evidences

Low-dose cyclical gallium nitrate reduced serum alkaline phosphatase and urinary markers of collagen turnover at higher doses in Paget's disease.

Trust comment: Pilot multicenter trial with clear dose-response biochemical effects but limited duration and heterogeneous prior therapies in participants.

Study Details

PMID:7852526
Participants:49
Impact:decreased (significant at 0.25 and 0.5 mg/kg/day)
Trust score:3/5

implant survival (1-year)

1 evidences

Randomized trial of equine-derived collagenated xenogeneic bone block (CXBB) versus autogenous bone block (ABB) for lateral ridge augmentation; 1-year implant survival and clinical/aesthetic outcomes showed no statistically significant differences.

Trust comment: Randomized controlled clinical study with 50 patients and 1-year follow-up; moderate quality but limited sample size for subgroup outcomes.

Study Details

PMID:37846853
Participants:50
Impact:78.6% (CXBB) vs 90.9% (ABB)
Trust score:4/5

pink aesthetic score (PES)

1 evidences

Randomized trial of equine-derived collagenated xenogeneic bone block (CXBB) versus autogenous bone block (ABB) for lateral ridge augmentation; 1-year implant survival and clinical/aesthetic outcomes showed no statistically significant differences.

Trust comment: Randomized controlled clinical study with 50 patients and 1-year follow-up; moderate quality but limited sample size for subgroup outcomes.

Study Details

PMID:37846853
Participants:50
Impact:8.5 (CXBB) vs 11.0 (ABB)
Trust score:4/5

de novo bone formation (%)

1 evidences

Multicenter randomized study of two bovine bone xenografts for socket preservation; all sites covered with a resorbable collagen membrane for 6 months, with similar histologic bone formation between groups.

Trust comment: Prospective multicenter randomized trial with 38 patients and histologic endpoints; reasonable quality though histologic variability and moderate sample size limit precision.

Study Details

PMID:24116363
Participants:38
Impact:Test (Endobon) 28.5% ± 20% vs Control (Bio-Oss) 31.4% ± 18%
Trust score:3/5

implant integration

1 evidences

Multicenter randomized study of two bovine bone xenografts for socket preservation; all sites covered with a resorbable collagen membrane for 6 months, with similar histologic bone formation between groups.

Trust comment: Prospective multicenter randomized trial with 38 patients and histologic endpoints; reasonable quality though histologic variability and moderate sample size limit precision.

Study Details

PMID:24116363
Participants:38
Impact:All but two implants integrated successfully after 1 year (no further numeric breakdown provided)
Trust score:3/5

alveolar bone width

1 evidences

Using deproteinised bovine bone mineral plus a resorbable collagen membrane after impacted third molar extraction improved alveolar bone dimensions and periodontal status versus natural healing.

Trust comment: Randomized clinical study with 99 patients and statistically significant outcomes reported, though effect sizes not fully detailed.

Study Details

PMID:37522232
Participants:99
Impact:significant increase vs control (P<0.05)
Trust score:4/5

alveolar bone height

1 evidences

Using deproteinised bovine bone mineral plus a resorbable collagen membrane after impacted third molar extraction improved alveolar bone dimensions and periodontal status versus natural healing.

Trust comment: Randomized clinical study with 99 patients and statistically significant outcomes reported, though effect sizes not fully detailed.

Study Details

PMID:37522232
Participants:99
Impact:significant increase vs control (P<0.05)
Trust score:4/5

augmented ridge horizontal width

1 evidences

Guided bone regeneration using particulate bone graft and a resorbable collagen membrane resulted in horizontal ridge width reduction during 6 months of healing; vertical level influenced reduction more than healing strategy.

Trust comment: Randomized clinical study with objective CBCT measurements but modest sample size (n=28) and limited long-term data.

Study Details

PMID:29283207
Participants:28
Impact:significant horizontal volume reduction during healing (statistically significant by vertical level; P=0.000)
Trust score:3/5

effect of healing strategy (submerged vs transmucosal)

1 evidences

Guided bone regeneration using particulate bone graft and a resorbable collagen membrane resulted in horizontal ridge width reduction during 6 months of healing; vertical level influenced reduction more than healing strategy.

Trust comment: Randomized clinical study with objective CBCT measurements but modest sample size (n=28) and limited long-term data.

Study Details

PMID:29283207
Participants:28
Impact:no significant effect on reduction width (P=0.182)
Trust score:3/5

All Bone (AB % of biopsy)

1 evidences

In this randomized trial, covering customized titanium mesh with a resorbable collagen membrane produced a small, non-significant increase in percentage of bone and a trend toward less residual graft material compared with mesh alone at 6 months.

Trust comment: Randomized, triple-blinded human RCT with rigorous micro-CT endpoints but small sample and low post-hoc power (~21%), limiting confidence in small differences.

Study Details

PMID:39106169
Participants:25
Impact:M+ 30.81% vs M− 27.68% → +3.13 percentage points (trend, non-significant)
Trust score:4/5

Residual graft material (MAT % of biopsy)

1 evidences

In this randomized trial, covering customized titanium mesh with a resorbable collagen membrane produced a small, non-significant increase in percentage of bone and a trend toward less residual graft material compared with mesh alone at 6 months.

Trust comment: Randomized, triple-blinded human RCT with rigorous micro-CT endpoints but small sample and low post-hoc power (~21%), limiting confidence in small differences.

Study Details

PMID:39106169
Participants:25
Impact:M+ 12.73% vs M− 15.58% → −2.85 percentage points (trend, non-significant)
Trust score:4/5

Non-mineralized tissue (NMT % of biopsy)

1 evidences

In this randomized trial, covering customized titanium mesh with a resorbable collagen membrane produced a small, non-significant increase in percentage of bone and a trend toward less residual graft material compared with mesh alone at 6 months.

Trust comment: Randomized, triple-blinded human RCT with rigorous micro-CT endpoints but small sample and low post-hoc power (~21%), limiting confidence in small differences.

Study Details

PMID:39106169
Participants:25
Impact:M+ 25.42% vs M− 25.24% → no meaningful difference
Trust score:4/5

primary patency

1 evidences

Compared autogenous basilic-brachial AVF to collagen-polyester prosthetic graft (Omniflow II) for hemodialysis access; prosthetic graft had quicker use but worse long-term outcomes.

Trust comment: Randomized comparison with moderate sample size; relevant to a collagen-containing prosthesis but limited power and detail for effect sizes.

Study Details

PMID:21803519
Participants:57
Impact:lower with collagen-polyester AVG (vs BBAVF; not quantified)
Trust score:3/5

secondary patency

1 evidences

Compared autogenous basilic-brachial AVF to collagen-polyester prosthetic graft (Omniflow II) for hemodialysis access; prosthetic graft had quicker use but worse long-term outcomes.

Trust comment: Randomized comparison with moderate sample size; relevant to a collagen-containing prosthesis but limited power and detail for effect sizes.

Study Details

PMID:21803519
Participants:57
Impact:lower with collagen-polyester AVG (vs BBAVF; SP difference not statistically significant)
Trust score:3/5

perifollicular collagen disruption

1 evidences

Examined scalp hair from patients receiving PUVA or narrowband UVB and found greater hair damage and disorganized perifollicular collagen after UV exposure, especially PUVA.

Trust comment: Small controlled observational sample with direct microscopy evidence; limited sample size but clear morphologic findings.

Study Details

PMID:24305423
Participants:30
Impact:increased (PUVA > NB-UVB > control; not quantified)
Trust score:3/5

hair follicle thickness

1 evidences

Examined scalp hair from patients receiving PUVA or narrowband UVB and found greater hair damage and disorganized perifollicular collagen after UV exposure, especially PUVA.

Trust comment: Small controlled observational sample with direct microscopy evidence; limited sample size but clear morphologic findings.

Study Details

PMID:24305423
Participants:30
Impact:reduced in UV-exposed groups (PUVA > NB-UVB; not quantified)
Trust score:3/5

hair follicle cell injury

1 evidences

Examined scalp hair from patients receiving PUVA or narrowband UVB and found greater hair damage and disorganized perifollicular collagen after UV exposure, especially PUVA.

Trust comment: Small controlled observational sample with direct microscopy evidence; limited sample size but clear morphologic findings.

Study Details

PMID:24305423
Participants:30
Impact:more nonspecific injury in PUVA group (vs NB-UVB and controls)
Trust score:3/5

carboxyterminal cross-linked peptide of type I collagen (CTX-I)

1 evidences

Oral clodronate for 2 years lowered type I collagen turnover biomarkers but did not change radiographic joint damage progression.

Trust comment: Randomized 2-year proof-of-concept trial with biomarker and radiographic endpoints; moderate quality though relatively small.

Study Details

PMID:22260818
Participants:60
Impact:decreased (p=0.03)
Trust score:4/5

aminoterminal propeptide of type I procollagen (P1NP)

1 evidences

Oral clodronate for 2 years lowered type I collagen turnover biomarkers but did not change radiographic joint damage progression.

Trust comment: Randomized 2-year proof-of-concept trial with biomarker and radiographic endpoints; moderate quality though relatively small.

Study Details

PMID:22260818
Participants:60
Impact:decreased (p=0.01)
Trust score:4/5

radiographic joint damage progression

1 evidences

Oral clodronate for 2 years lowered type I collagen turnover biomarkers but did not change radiographic joint damage progression.

Trust comment: Randomized 2-year proof-of-concept trial with biomarker and radiographic endpoints; moderate quality though relatively small.

Study Details

PMID:22260818
Participants:60
Impact:no difference (clodronate vs control over 24 months)
Trust score:4/5

1-week postoperative complications

1 evidences

Adding a gentamicin–collagen sponge to primary excision reduced early (1-week) postoperative complications but did not change long-term recurrence.

Trust comment: Large prospective randomized study with clear early outcome differences; good applicability for collagen-based local delivery but some outcomes counterintuitive (healing time).

Study Details

PMID:18093197
Participants:200
Impact:reduced in gentamicin–collagen sponge group: 35% vs 52% (−17 percentage points)
Trust score:4/5

3-month complications

1 evidences

Adding a gentamicin–collagen sponge to primary excision reduced early (1-week) postoperative complications but did not change long-term recurrence.

Trust comment: Large prospective randomized study with clear early outcome differences; good applicability for collagen-based local delivery but some outcomes counterintuitive (healing time).

Study Details

PMID:18093197
Participants:200
Impact:similar but slightly lower in sponge group: 12% vs 19% (−7 percentage points)
Trust score:4/5

time to outpatient discharge

1 evidences

Randomized trial of a collagen-based arterial closure device showing faster hemostasis and earlier discharge with similar complication rates.

Trust comment: Randomized controlled trial (n=304) directly tested a collagen hemostatic device with clear primary outcome differences; single good-quality RCT evidence.

Study Details

PMID:9514451
Participants:304
Impact:−2.7 h (5.0 ± 4 vs 7.7 ± 4 h; p=0.0001)
Trust score:4/5

bleeding/vascular complications

1 evidences

Randomized trial of a collagen-based arterial closure device showing faster hemostasis and earlier discharge with similar complication rates.

Trust comment: Randomized controlled trial (n=304) directly tested a collagen hemostatic device with clear primary outcome differences; single good-quality RCT evidence.

Study Details

PMID:9514451
Participants:304
Impact:no significant difference (9% vs 6%; p=0.397)
Trust score:4/5

hemostasis at 3 minutes

1 evidences

A collagen-containing powder (CP) achieved hemostasis more often and faster preparation than a control hemostatic matrix in cardiothoracic surgery.

Trust comment: Randomized multicenter RCT with objective endpoints but notable author/company conflicts of interest disclosed.

Study Details

PMID:31763732
Participants:105
Impact:+54.5% (64.2% vs 9.6%)
Trust score:4/5

hemostasis at 5 minutes

1 evidences

A collagen-containing powder (CP) achieved hemostasis more often and faster preparation than a control hemostatic matrix in cardiothoracic surgery.

Trust comment: Randomized multicenter RCT with objective endpoints but notable author/company conflicts of interest disclosed.

Study Details

PMID:31763732
Participants:105
Impact:+48.2% (92.5% vs 44.2%)
Trust score:4/5

device preparation time

1 evidences

A collagen-containing powder (CP) achieved hemostasis more often and faster preparation than a control hemostatic matrix in cardiothoracic surgery.

Trust comment: Randomized multicenter RCT with objective endpoints but notable author/company conflicts of interest disclosed.

Study Details

PMID:31763732
Participants:105
Impact:-~127s (19.5s vs 146.4s)
Trust score:4/5

Crow's feet number and area (wrinkle reduction)

1 evidences

Topical cyclized collagen-derived peptide (CHP-9) applied twice daily for 56 days improved wrinkles, elasticity, pigmentation, hydration and barrier function and outperformed low-dose retinol and vehicle without reported adverse events.

Trust comment: Well-designed randomized, double-blind, vehicle- and active-controlled clinical trial with 96 randomized and 91 completers and objective instrument measures, supporting high trustworthiness.

Study Details

PMID:40586182
Participants:91
Impact:Number −2.20 (mean) vs control; area −3.95 mm² at Day 56 (CHP-9 vs control)
Trust score:5/5

Forehead wrinkles number and area

1 evidences

Topical cyclized collagen-derived peptide (CHP-9) applied twice daily for 56 days improved wrinkles, elasticity, pigmentation, hydration and barrier function and outperformed low-dose retinol and vehicle without reported adverse events.

Trust comment: Well-designed randomized, double-blind, vehicle- and active-controlled clinical trial with 96 randomized and 91 completers and objective instrument measures, supporting high trustworthiness.

Study Details

PMID:40586182
Participants:91
Impact:Number −2.88 and area −4.90 mm² at Day 56 (CHP-9 vs control)
Trust score:5/5

Skin hydration and TEWL (barrier function)

1 evidences

Topical cyclized collagen-derived peptide (CHP-9) applied twice daily for 56 days improved wrinkles, elasticity, pigmentation, hydration and barrier function and outperformed low-dose retinol and vehicle without reported adverse events.

Trust comment: Well-designed randomized, double-blind, vehicle- and active-controlled clinical trial with 96 randomized and 91 completers and objective instrument measures, supporting high trustworthiness.

Study Details

PMID:40586182
Participants:91
Impact:Hydration +9.44 c.u.; TEWL −3.93 g/h/m² at Day 56 (CHP-9 vs control)
Trust score:5/5

Achilles tendon length change

1 evidences

Compared tendon and muscle stretch during walking in long-term diabetes patients versus controls; tendon length changes were reduced in diabetes and related to diabetes duration.

Trust comment: Small observational study with objective measurements but limited sample size and cross-sectional design.

Study Details

PMID:20193974
Participants:25
Impact:attenuated in diabetes vs controls
Trust score:3/5

Ankle range of motion

1 evidences

Compared tendon and muscle stretch during walking in long-term diabetes patients versus controls; tendon length changes were reduced in diabetes and related to diabetes duration.

Trust comment: Small observational study with objective measurements but limited sample size and cross-sectional design.

Study Details

PMID:20193974
Participants:25
Impact:decreased in diabetes; inversely correlated with diabetes duration (r=-0.693)
Trust score:3/5

Tendon length vs diabetes duration

1 evidences

Compared tendon and muscle stretch during walking in long-term diabetes patients versus controls; tendon length changes were reduced in diabetes and related to diabetes duration.

Trust comment: Small observational study with objective measurements but limited sample size and cross-sectional design.

Study Details

PMID:20193974
Participants:25
Impact:inverse correlation (r=-0.628; P<0.05)
Trust score:3/5

Postextraction bleeding rate

1 evidences

Randomized trial in anticoagulated patients undergoing simple dental extractions; local hemostasis with resorbable collagen sponges was used in the group maintaining oral anticoagulation.

Trust comment: Randomized prospective trial with substantial sample size and clinically relevant endpoints, though bleeding events were few.

Study Details

PMID:19375008
Participants:214
Impact:Group A (continuous OAT) 7.34% vs Group B (bridging) 4.76% (no significant difference)
Trust score:4/5

Thromboembolic complications

1 evidences

Randomized trial in anticoagulated patients undergoing simple dental extractions; local hemostasis with resorbable collagen sponges was used in the group maintaining oral anticoagulation.

Trust comment: Randomized prospective trial with substantial sample size and clinically relevant endpoints, though bleeding events were few.

Study Details

PMID:19375008
Participants:214
Impact:none reported in either group (0%)
Trust score:4/5

Local hemostasis with collagen sponge

1 evidences

Randomized trial in anticoagulated patients undergoing simple dental extractions; local hemostasis with resorbable collagen sponges was used in the group maintaining oral anticoagulation.

Trust comment: Randomized prospective trial with substantial sample size and clinically relevant endpoints, though bleeding events were few.

Study Details

PMID:19375008
Participants:214
Impact:effective to control mild bleeding without suturing in OAT group
Trust score:4/5

Macroaggregation to collagen

1 evidences

Examined how heparinization and storage conditions affect platelet aggregation responses to collagen in patients undergoing coronary bypass; platelet macroaggregation to collagen was depressed after heparin and by storage.

Trust comment: Randomized allocation and objective assays but small sample and specialized setting limit generalizability.

Study Details

PMID:16884986
Participants:27
Impact:decreased from median 16.3 Ω ex vivo to 8.9 Ω after heparin (P<0.0001)
Trust score:3/5

Effect of CPDA storage

1 evidences

Examined how heparinization and storage conditions affect platelet aggregation responses to collagen in patients undergoing coronary bypass; platelet macroaggregation to collagen was depressed after heparin and by storage.

Trust comment: Randomized allocation and objective assays but small sample and specialized setting limit generalizability.

Study Details

PMID:16884986
Participants:27
Impact:marked deterioration in platelet function (macro- and microaggregation reduced)
Trust score:3/5

Biceps brachii CSA and thickness

1 evidences

Double-blind RCT: a multi-ingredient supplement (included 300 mg calcium citrate) plus resistance training increased lean body mass and some upper-body muscle size measures more than an isonitrogenous placebo.

Trust comment: Double-blind randomized trial with objective outcomes but small sample size limits precision.

Study Details

PMID:33756525
Participants:26
Impact:increased in SUPP vs PL (P<0.05)
Trust score:3/5

Paretic eccentric knee extensor work

1 evidences

Randomized trial of two whole-body vibration frequencies (20 Hz vs 30 Hz) in chronic stroke patients; both increased knee strength and reduced bone resorption (NTx), with 30 Hz showing greater paretic eccentric strength gains.

Trust comment: Well-powered randomized trial with blinded assessors and intention-to-treat analysis, though no sham control and limited generalizability beyond sample.

Study Details

PMID:33420277
Participants:80
Impact:20 Hz +7.8 J vs 30 Hz +13.8 J; between-group difference 5.9 J (95% CI 0.05,11.8), P<0.05
Trust score:4/5

6MWT distance

1 evidences

Randomized trial of two whole-body vibration frequencies (20 Hz vs 30 Hz) in chronic stroke patients; both increased knee strength and reduced bone resorption (NTx), with 30 Hz showing greater paretic eccentric strength gains.

Trust comment: Well-powered randomized trial with blinded assessors and intention-to-treat analysis, though no sham control and limited generalizability beyond sample.

Study Details

PMID:33420277
Participants:80
Impact:no significant change between groups (no effect)
Trust score:4/5

Michigan Hand Outcomes Questionnaire (MHQ) total score

1 evidences

Compared thumb trapeziectomy using patient's tendon versus a human dermal collagen allograft; both improved hand outcome scores similarly but the allograft group had more complications.

Trust comment: Randomized controlled trial with 12-month follow-up and clear outcomes; credible design but modest sample size and single-center limits generalizability.

Study Details

PMID:28899589
Participants:60
Impact:+32 points (FCR) vs +23 points (allograft) at 12 months
Trust score:4/5

Complication count

1 evidences

Compared thumb trapeziectomy using patient's tendon versus a human dermal collagen allograft; both improved hand outcome scores similarly but the allograft group had more complications.

Trust comment: Randomized controlled trial with 12-month follow-up and clear outcomes; credible design but modest sample size and single-center limits generalizability.

Study Details

PMID:28899589
Participants:60
Impact:5 complications (FCR) vs 10 complications (allograft) over 12 months
Trust score:4/5

Revision surgery

1 evidences

Compared thumb trapeziectomy using patient's tendon versus a human dermal collagen allograft; both improved hand outcome scores similarly but the allograft group had more complications.

Trust comment: Randomized controlled trial with 12-month follow-up and clear outcomes; credible design but modest sample size and single-center limits generalizability.

Study Details

PMID:28899589
Participants:60
Impact:1 revision required in allograft group
Trust score:4/5

METAVIR fibrosis stage improvement (≥1 stage at Week 12)

1 evidences

Weekly IV BMS-986263 (HSP47 siRNA LNP) for 12 weeks produced target engagement and fibrosis improvement in some patients with advanced hepatic fibrosis and was generally well tolerated.

Trust comment: Randomized, double-blind placebo-controlled Phase 2 with clear histologic and biomarker endpoints but single-center and small sample size limits generalizability.

Study Details

PMID:34605045
Participants:61
Impact:Placebo 13% (2/15); 45 mg 17% (3/18); 90 mg 21% (6/28)
Trust score:4/5

HSP47 mRNA (median % change, Week 12 vs baseline)

1 evidences

Weekly IV BMS-986263 (HSP47 siRNA LNP) for 12 weeks produced target engagement and fibrosis improvement in some patients with advanced hepatic fibrosis and was generally well tolerated.

Trust comment: Randomized, double-blind placebo-controlled Phase 2 with clear histologic and biomarker endpoints but single-center and small sample size limits generalizability.

Study Details

PMID:34605045
Participants:61
Impact:Placebo +13.7%; 45 mg −1.2%; 90 mg −5.9%
Trust score:4/5

HSP47 protein (median % change, Week 12 vs baseline)

1 evidences

Weekly IV BMS-986263 (HSP47 siRNA LNP) for 12 weeks produced target engagement and fibrosis improvement in some patients with advanced hepatic fibrosis and was generally well tolerated.

Trust comment: Randomized, double-blind placebo-controlled Phase 2 with clear histologic and biomarker endpoints but single-center and small sample size limits generalizability.

Study Details

PMID:34605045
Participants:61
Impact:Placebo +23.5%; 45 mg −11.3%; 90 mg −10.1%
Trust score:4/5

seroma rate

1 evidences

RCT comparing ADM with vs without basement membrane in immediate prepectoral breast reconstruction: no significant differences in overall complications or shape change; seromas more frequent with basement membrane (10% vs 0%).

Trust comment: Randomized single‑blind trial with moderate sample size directly assessing collagen-containing matrix modifications; limited by borderline/non-significant P for seroma and overall outcome similarity.

Study Details

PMID:39314097
Participants:56
Impact:10% (ADM with basement membrane) vs 0% (without); P = 0.09
Trust score:3/5

mechanical properties (tensile strength/elasticity)

1 evidences

RCT comparing ADM with vs without basement membrane in immediate prepectoral breast reconstruction: no significant differences in overall complications or shape change; seromas more frequent with basement membrane (10% vs 0%).

Trust comment: Randomized single‑blind trial with moderate sample size directly assessing collagen-containing matrix modifications; limited by borderline/non-significant P for seroma and overall outcome similarity.

Study Details

PMID:39314097
Participants:56
Impact:ADM without basement membrane showed lower tensile strength and higher elasticity
Trust score:3/5

TIMP-1 (tissue inhibitor of MMP-1)

1 evidences

In >1,100 HFpEF patients sacubitril/valsartan (vs valsartan) favorably altered circulating extracellular matrix/collagen-related biomarkers at 16 weeks.

Trust comment: Large randomized trial (PARAGON-HF) with >1,100 participants and serial biomarker measurement; high sample size but biomarkers are surrogate endpoints.

Study Details

PMID:32731928
Participants:1135
Impact:−8% vs valsartan at 16 weeks (95% CI 6%–10%; p<0.001)
Trust score:4/5

N-terminal propeptide of collagen III

1 evidences

In >1,100 HFpEF patients sacubitril/valsartan (vs valsartan) favorably altered circulating extracellular matrix/collagen-related biomarkers at 16 weeks.

Trust comment: Large randomized trial (PARAGON-HF) with >1,100 participants and serial biomarker measurement; high sample size but biomarkers are surrogate endpoints.

Study Details

PMID:32731928
Participants:1135
Impact:−3% vs valsartan at 16 weeks (95% CI 0%–6%; p=0.04)
Trust score:4/5

procollagen III peptide (PIIIP)

1 evidences

Adding Clostridium butyricum to rosuvastatin in NAFLD patients improved gut microbiota composition and reduced lipids, liver enzymes, fibrosis markers and inflammatory cytokines compared with rosuvastatin alone.

Trust comment: Randomized study in 96 patients reporting multiple biomarker improvements but limited methodological detail and potential bias risk.

Study Details

PMID:35869734
Participants:96
Impact:decreased vs control (p<0.05)
Trust score:3/5

collagen IV

1 evidences

Adding Clostridium butyricum to rosuvastatin in NAFLD patients improved gut microbiota composition and reduced lipids, liver enzymes, fibrosis markers and inflammatory cytokines compared with rosuvastatin alone.

Trust comment: Randomized study in 96 patients reporting multiple biomarker improvements but limited methodological detail and potential bias risk.

Study Details

PMID:35869734
Participants:96
Impact:decreased vs control (p<0.05)
Trust score:3/5

C2C (collagen type II cleavage)

1 evidences

Randomized double-blind 30-day trial (67 completers) found Aflapin reduced knee pain and improved function; collagen type II cleavage biomarker (C2C) and inflammatory biomarkers decreased.

Trust comment: Randomized, double-blind, placebo-controlled trial with objective biomarker and clinical endpoints but small, short-duration study.

Study Details

PMID:35512759
Participants:67
Impact:decreased (significant reduction vs baseline/placebo)
Trust score:4/5

hyaluronic acid content

1 evidences

A 12-week study in women with photodamaged skin showing improved skin hydration and increased HA and collagen gene expression after topical serum use.

Trust comment: Single-center clinical study with objective bioinstrumentation and biopsy-based PCR but modest sample size and limited randomization/control for the main cohort.

Study Details

PMID:28915283
Participants:59
Impact:increase (significant after 4 weeks)
Trust score:3/5

collagen type 1a1 expression

1 evidences

A 12-week study in women with photodamaged skin showing improved skin hydration and increased HA and collagen gene expression after topical serum use.

Trust comment: Single-center clinical study with objective bioinstrumentation and biopsy-based PCR but modest sample size and limited randomization/control for the main cohort.

Study Details

PMID:28915283
Participants:59
Impact:increase (significant after 12 weeks)
Trust score:3/5

skin hydration / transepidermal water loss

1 evidences

A 12-week study in women with photodamaged skin showing improved skin hydration and increased HA and collagen gene expression after topical serum use.

Trust comment: Single-center clinical study with objective bioinstrumentation and biopsy-based PCR but modest sample size and limited randomization/control for the main cohort.

Study Details

PMID:28915283
Participants:59
Impact:improved hydration and decreased TEWL (significant at week 12)
Trust score:3/5

Clinical functional scores (knee cartilage repair)

1 evidences

Randomized trial comparing AMIC (uses a type I/III collagen membrane) versus microfracture for knee cartilage lesions; AMIC showed sustained clinical benefit at 5 years.

Trust comment: Randomized multicenter trial with 5-year follow-up using a collagen membrane implant; moderate sample size but robust follow-up supports moderate-to-high trust.

Study Details

PMID:28108777
Participants:47
Impact:AMIC groups: stable improvement for ≥5 years; microfracture: progressive and significant degradation by 5 years
Trust score:4/5

MRI defect filling

1 evidences

Randomized trial comparing AMIC (uses a type I/III collagen membrane) versus microfracture for knee cartilage lesions; AMIC showed sustained clinical benefit at 5 years.

Trust comment: Randomized multicenter trial with 5-year follow-up using a collagen membrane implant; moderate sample size but robust follow-up supports moderate-to-high trust.

Study Details

PMID:28108777
Participants:47
Impact:More complete defect filling in AMIC groups at 2 and 5 years
Trust score:4/5

Median healing time

1 evidences

Prospective randomized trial comparing donor-site dressings including an equine collagen foil; collagen foil showed similar healing time and scarring to other dressings.

Trust comment: Randomized prospective trial including an equine collagen dressing; small sample and minimal between-group differences limit strength of conclusions.

Study Details

PMID:16679905
Participants:33
Impact:Collagen foil (Tissu Foil E): median 19 days (same as Vaseline gauze), longer than OD (14 days) and Biobrane (16 days)
Trust score:3/5

Scar pliability/scarring (VSS and cutometer)

1 evidences

Prospective randomized trial comparing donor-site dressings including an equine collagen foil; collagen foil showed similar healing time and scarring to other dressings.

Trust comment: Randomized prospective trial including an equine collagen dressing; small sample and minimal between-group differences limit strength of conclusions.

Study Details

PMID:16679905
Participants:33
Impact:No significant difference between dressing groups; donor sites differed from uninjured skin on objective measures
Trust score:3/5

Repigmentation

1 evidences

Adding collagenase to trypsin during hair follicle cell suspension preparation increased pigment-cell retrieval and led to greater repigmentation of vitiligo patches over 6 months.

Trust comment: Randomized double-blind pilot RCT in 22 human patients; small sample size limits precision but design is sound.

Study Details

PMID:31361909
Participants:22
Impact:+16.6 percentage points (33.22% vs 16.59%, trypsin+collagenase vs dermabrasion)
Trust score:3/5

Cell yield

1 evidences

Adding collagenase to trypsin during hair follicle cell suspension preparation increased pigment-cell retrieval and led to greater repigmentation of vitiligo patches over 6 months.

Trust comment: Randomized double-blind pilot RCT in 22 human patients; small sample size limits precision but design is sound.

Study Details

PMID:31361909
Participants:22
Impact:Increased (significant) with addition of collagenase
Trust score:3/5

Cell viability

1 evidences

Adding collagenase to trypsin during hair follicle cell suspension preparation increased pigment-cell retrieval and led to greater repigmentation of vitiligo patches over 6 months.

Trust comment: Randomized double-blind pilot RCT in 22 human patients; small sample size limits precision but design is sound.

Study Details

PMID:31361909
Participants:22
Impact:No change (comparable viability)
Trust score:3/5

Soft tissue healing rate

1 evidences

In 22 patients, autologous concentrated growth factor (CGF) membranes produced faster soft-tissue healing and higher microvessel density than Bio-Gide collagen membranes, while alveolar bone preservation was similar between groups.

Trust comment: Randomized controlled trial in humans comparing CGF to collagen membrane with objective measures but small sample (22 patients) limits generalizability.

Study Details

PMID:36316617
Participants:22
Impact:Day 7: 60.51% vs 38.38% (CGF vs Bio-Gide, P=0.003); Day 14: 89.10% vs 61.73% (P<0.001)
Trust score:4/5

Microvessel density

1 evidences

In 22 patients, autologous concentrated growth factor (CGF) membranes produced faster soft-tissue healing and higher microvessel density than Bio-Gide collagen membranes, while alveolar bone preservation was similar between groups.

Trust comment: Randomized controlled trial in humans comparing CGF to collagen membrane with objective measures but small sample (22 patients) limits generalizability.

Study Details

PMID:36316617
Participants:22
Impact:Higher with CGF (35.32 vs 22.93, P<0.001)
Trust score:4/5

resistin level

1 evidences

Study of postmenopausal RA patients (both groups received vitamin D3 and calcium) found resistin associated with markers of inflammation and reduced BMD; HRT transiently increased resistin in year 1.

Trust comment: Randomized allocation to HRT vs control with validated biomarker assays and 2-year follow-up, but findings are associative.

Study Details

PMID:18511473
Participants:88
Impact:no difference vs healthy controls; increased with HRT in year 1 only
Trust score:4/5

IL-1Ra level

1 evidences

Study of postmenopausal RA patients (both groups received vitamin D3 and calcium) found resistin associated with markers of inflammation and reduced BMD; HRT transiently increased resistin in year 1.

Trust comment: Randomized allocation to HRT vs control with validated biomarker assays and 2-year follow-up, but findings are associative.

Study Details

PMID:18511473
Participants:88
Impact:positively correlated with resistin
Trust score:4/5

buccal vertical bone resorption

1 evidences

In 30 patients, ridge preservation using deproteinized bovine bone mineral plus a collagen matrix reduced coronal horizontal bone loss vs spontaneous healing; immediate implant placement did not add further benefit.

Trust comment: Randomized clinical trial with CBCT quantification (n=30); collagen matrix was part of a combined ARP treatment so its isolated contribution is uncertain.

Study Details

PMID:31050359
Participants:30
Impact:no significant differences between groups
Trust score:4/5

coronal horizontal bone loss

1 evidences

In 30 patients, ridge preservation using deproteinized bovine bone mineral plus a collagen matrix reduced coronal horizontal bone loss vs spontaneous healing; immediate implant placement did not add further benefit.

Trust comment: Randomized clinical trial with CBCT quantification (n=30); collagen matrix was part of a combined ARP treatment so its isolated contribution is uncertain.

Study Details

PMID:31050359
Participants:30
Impact:SH: -3.37 mm (-43.2%); DBBM/CM: -1.56 mm (-19.2%); IMPL/DBBM/CM: -1.29 mm (-14.9%) (DBBM/CM and IMPL groups better than SH)
Trust score:4/5

ridge width at 1/3/5 mm

1 evidences

In 30 patients, ridge preservation using deproteinized bovine bone mineral plus a collagen matrix reduced coronal horizontal bone loss vs spontaneous healing; immediate implant placement did not add further benefit.

Trust comment: Randomized clinical trial with CBCT quantification (n=30); collagen matrix was part of a combined ARP treatment so its isolated contribution is uncertain.

Study Details

PMID:31050359
Participants:30
Impact:overall preservation improved with DBBM+collagen matrix vs spontaneous healing (no exact values for all levels shown)
Trust score:4/5

Muscle protein synthesis rate (myofibrillar FSR)

1 evidences

One-year randomized trial including a daily bovine collagen supplement arm; assessed muscle protein synthesis and muscle metabolome.

Trust comment: Randomized, blinded supplement arms including collagen, moderate sample (n=66) and rigorous tracer methods; limited by dropout and small per-protocol subgroup sizes.

Study Details

PMID:37266586
Participants:66
Impact:No significant change with collagen supplementation (mITT ΔΔ FSR for COLL −0.0001 %·h⁻¹; PP 0.0013 %·h⁻¹)
Trust score:4/5

Muscle metabolome

1 evidences

One-year randomized trial including a daily bovine collagen supplement arm; assessed muscle protein synthesis and muscle metabolome.

Trust comment: Randomized, blinded supplement arms including collagen, moderate sample (n=66) and rigorous tracer methods; limited by dropout and small per-protocol subgroup sizes.

Study Details

PMID:37266586
Participants:66
Impact:No significant differences between collagen and other groups at 12 months
Trust score:4/5

CTX1 (bone resorption marker)

1 evidences

In people with relapsing-remitting MS, weekly high-dose vitamin D raised vitamin D levels but did not meaningfully change common blood markers of bone formation or resorption over 96 weeks.

Trust comment: Randomized controlled trial in humans with 68 completers and appropriate marker measurements; limited size reduces sensitivity to small effects.

Study Details

PMID:28376767
Participants:68
Impact:No significant change (−6.68% at 48w; −3.60% at 96w; p>0.05)
Trust score:4/5

WOMAC score (symptoms/function)

1 evidences

In 96 KOA patients, acupuncture±moxibustion improved symptoms and reduced markers of cartilage turnover and MMP/TIMP imbalance.

Trust comment: Randomized clinical trial with 96 patients showing biomarker and symptom changes; reporting details and blinding unclear, limiting certainty.

Study Details

PMID:35319845
Participants:96
Impact:Decreased after treatment (p<0.05)
Trust score:3/5

CTX‑I (type I collagen C‑terminal peptide)

1 evidences

In 96 KOA patients, acupuncture±moxibustion improved symptoms and reduced markers of cartilage turnover and MMP/TIMP imbalance.

Trust comment: Randomized clinical trial with 96 patients showing biomarker and symptom changes; reporting details and blinding unclear, limiting certainty.

Study Details

PMID:35319845
Participants:96
Impact:Decreased after treatment (p<0.05)
Trust score:3/5

MMP‑9 and TIMP‑1 (matrix remodeling)

1 evidences

In 96 KOA patients, acupuncture±moxibustion improved symptoms and reduced markers of cartilage turnover and MMP/TIMP imbalance.

Trust comment: Randomized clinical trial with 96 patients showing biomarker and symptom changes; reporting details and blinding unclear, limiting certainty.

Study Details

PMID:35319845
Participants:96
Impact:Both decreased and MMP‑9/TIMP‑1 ratio decreased (p<0.05)
Trust score:3/5

Perimeter of collagen fibres (q‑FP)

1 evidences

In a large NAFLD biopsy cohort, automated dual‑photon measurements of collagen-related features accurately quantified fibrosis stage and predicted outcomes.

Trust comment: Large histological cohort with objective, validated automated collagen metrics and external validation; strong methodology for the stated aim.

Study Details

PMID:31563875
Participants:344
Impact:High accuracy for fibrosis stage (AUC >0.90); sensitivity 88.3%–96.2% at optimal cutoffs
Trust score:4/5

Number of long collagen fibres (q‑FP)

1 evidences

In a large NAFLD biopsy cohort, automated dual‑photon measurements of collagen-related features accurately quantified fibrosis stage and predicted outcomes.

Trust comment: Large histological cohort with objective, validated automated collagen metrics and external validation; strong methodology for the stated aim.

Study Details

PMID:31563875
Participants:344
Impact:High accuracy for fibrosis stage (AUC >0.90); specificity 78.1%–91.1% at optimal cutoffs
Trust score:4/5

q‑FP changes over time

1 evidences

In a large NAFLD biopsy cohort, automated dual‑photon measurements of collagen-related features accurately quantified fibrosis stage and predicted outcomes.

Trust comment: Large histological cohort with objective, validated automated collagen metrics and external validation; strong methodology for the stated aim.

Study Details

PMID:31563875
Participants:344
Impact:Changes in q‑FPs associated with changes in fibrosis stage and predicted liver‑related events
Trust score:4/5

Dermal collagen intensity

1 evidences

In a small double‑blind RCT, multispectral LED treatment did not show overall superiority vs sham for grade‑2 sacral pressure ulcers; LED increased epidermal thickness and basement membrane measures but wound area changes were similar.

Trust comment: Double‑blind RCT with biopsies and objective measures but small sample, dropout, and baseline imbalances limit generalizability.

Study Details

PMID:39178286
Participants:27
Impact:Increased in both groups but no significant between‑group difference (p=0.112)
Trust score:3/5

Vulvovaginal Symptom Questionnaire (VSQ)

1 evidences

In 31 postmenopausal women, RF and hybrid fractional laser produced subjective improvements in vulvovaginal symptoms and sexual function domains; biopsies showed decreased expression of collagen I and other ECM genes.

Trust comment: Randomized placebo‑controlled trial with objective and subjective outcomes but small sample size limits precision of estimates.

Study Details

PMID:35882474
Participants:31
Impact:Mean VSQ score decreased (improvement) at 3 months: placebo −2.93; dual −4.07; HFL −4.78 (statistically significant)
Trust score:4/5

Sexual function (FSFI domains)

1 evidences

In 31 postmenopausal women, RF and hybrid fractional laser produced subjective improvements in vulvovaginal symptoms and sexual function domains; biopsies showed decreased expression of collagen I and other ECM genes.

Trust comment: Randomized placebo‑controlled trial with objective and subjective outcomes but small sample size limits precision of estimates.

Study Details

PMID:35882474
Participants:31
Impact:Improvements in desire (placebo/dual) and multiple domains (HFL) at 3 and 6 months
Trust score:4/5

Collagen I / elastin / lysyl oxidase gene expression

1 evidences

In 31 postmenopausal women, RF and hybrid fractional laser produced subjective improvements in vulvovaginal symptoms and sexual function domains; biopsies showed decreased expression of collagen I and other ECM genes.

Trust comment: Randomized placebo‑controlled trial with objective and subjective outcomes but small sample size limits precision of estimates.

Study Details

PMID:35882474
Participants:31
Impact:Decreased expression after treatments (suggesting no new ECM production)
Trust score:4/5

leukocyte count

1 evidences

Sixty patients receiving either gelatin-sealed (Gelseal) or collagen-sealed (Hemashield) aortic grafts: gelatin group showed higher leukocyte counts in the second week, differences resolved by day 21.

Trust comment: Randomized prospective trial in 60 patients comparing collagen-sealed vs gelatin-sealed grafts with serial inflammatory markers; moderate-high quality.

Study Details

PMID:9219480
Participants:60
Impact:higher in Gelseal (gelatin) versus Hemashield (collagen) on postoperative days 7 and 14; no difference by day 21
Trust score:4/5

body temperature / platelet count

1 evidences

Sixty patients receiving either gelatin-sealed (Gelseal) or collagen-sealed (Hemashield) aortic grafts: gelatin group showed higher leukocyte counts in the second week, differences resolved by day 21.

Trust comment: Randomized prospective trial in 60 patients comparing collagen-sealed vs gelatin-sealed grafts with serial inflammatory markers; moderate-high quality.

Study Details

PMID:9219480
Participants:60
Impact:both groups had low-grade fever and biphasic platelet changes early postoperatively
Trust score:4/5

anatomical success rate

1 evidences

Randomized multicenter trial comparing collagen-coated polypropylene mesh versus anterior colporrhaphy for anterior vaginal wall prolapse; mesh had higher 1-year anatomical success but some mesh-related morbidity.

Trust comment: Multicenter randomized controlled trial with 12-month follow-up showing clear anatomical differences but some mesh-specific morbidity.

Study Details

PMID:23512113
Participants:147
Impact:+25 percentage points (89% vs 64%)
Trust score:4/5

anatomical/functional recurrence

1 evidences

Randomized multicenter trial comparing collagen-coated polypropylene mesh versus anterior colporrhaphy for anterior vaginal wall prolapse; mesh had higher 1-year anatomical success but some mesh-related morbidity.

Trust comment: Multicenter randomized controlled trial with 12-month follow-up showing clear anatomical differences but some mesh-specific morbidity.

Study Details

PMID:23512113
Participants:147
Impact:−20.9 percentage points (31.3% vs 52.2%)
Trust score:4/5

mesh erosion rate

1 evidences

Randomized multicenter trial comparing collagen-coated polypropylene mesh versus anterior colporrhaphy for anterior vaginal wall prolapse; mesh had higher 1-year anatomical success but some mesh-related morbidity.

Trust comment: Multicenter randomized controlled trial with 12-month follow-up showing clear anatomical differences but some mesh-specific morbidity.

Study Details

PMID:23512113
Participants:147
Impact:9.5% (erosion incidence)
Trust score:4/5

postoperative Voice Handicap Index (VHI)

1 evidences

Randomized trial comparing LigaSure (creates a collagen seal) versus conventional clips/ties in thyroidectomy; no change in operative time, improved postoperative VHI with LigaSure, but substantially higher device cost.

Trust comment: Small randomized trial with objective and subjective outcomes but limited power due to small sample size.

Study Details

PMID:20643002
Participants:28
Impact:−13.26 points (19.83 vs 6.57; p=0.041) favoring LigaSure
Trust score:3/5

operative cost

1 evidences

Randomized trial comparing LigaSure (creates a collagen seal) versus conventional clips/ties in thyroidectomy; no change in operative time, improved postoperative VHI with LigaSure, but substantially higher device cost.

Trust comment: Small randomized trial with objective and subjective outcomes but limited power due to small sample size.

Study Details

PMID:20643002
Participants:28
Impact:+US$313.55 (US$387.15 vs US$73.60)
Trust score:3/5

periodontal probing depth

1 evidences

Randomized allocation of 30 defects in 25 patients to graft alone, graft+PRP, and graft+PRP+membrane; all treatments improved clinical measures similarly with no added clinical benefit from PRP.

Trust comment: Small randomized allocation by defect with objective measures but limited sample size and defect-based randomization.

Study Details

PMID:17470012
Participants:25
Impact:improved in all groups with no significant between-group differences
Trust score:3/5

radiographic bone measures

1 evidences

Randomized allocation of 30 defects in 25 patients to graft alone, graft+PRP, and graft+PRP+membrane; all treatments improved clinical measures similarly with no added clinical benefit from PRP.

Trust comment: Small randomized allocation by defect with objective measures but limited sample size and defect-based randomization.

Study Details

PMID:17470012
Participants:25
Impact:no significant differences among groups at follow-up
Trust score:3/5

intraoperative air-leak reduction

1 evidences

Multicenter randomized trial of an absorbable fibrin sealant patch (collagen sponge coated with fibrin) versus standard treatment after pulmonary resection; AFSP reduced intraoperative leak intensity and postoperative leak duration and was well tolerated.

Trust comment: Large multicenter randomized study with clinically relevant endpoints and statistically significant primary/secondary results.

Study Details

PMID:24193288
Participants:346
Impact:+8.5 percentage points (90.5% vs 82.0%; p=0.03) favoring AFSP
Trust score:4/5

postoperative air leakage duration

1 evidences

Multicenter randomized trial of an absorbable fibrin sealant patch (collagen sponge coated with fibrin) versus standard treatment after pulmonary resection; AFSP reduced intraoperative leak intensity and postoperative leak duration and was well tolerated.

Trust comment: Large multicenter randomized study with clinically relevant endpoints and statistically significant primary/secondary results.

Study Details

PMID:24193288
Participants:346
Impact:significantly reduced in AFSP group (p=0.0437)
Trust score:4/5

time to chest-drain removal

1 evidences

Multicenter randomized trial of an absorbable fibrin sealant patch (collagen sponge coated with fibrin) versus standard treatment after pulmonary resection; AFSP reduced intraoperative leak intensity and postoperative leak duration and was well tolerated.

Trust comment: Large multicenter randomized study with clinically relevant endpoints and statistically significant primary/secondary results.

Study Details

PMID:24193288
Participants:346
Impact:median 6 vs 7 days (AFSP vs ST), not significant (p=0.38)
Trust score:4/5

urinary NTX (type I collagen cross-linked N-telopeptide)

1 evidences

Randomized substudy comparing tamoxifen, exemestane, and anastrozole over 2 years; tamoxifen was associated with lower bone turnover markers (NTX and BAP) versus the two aromatase inhibitors, with BMD trends favoring tamoxifen though not always significant.

Trust comment: Randomized substudy with objective bone markers but limited sample size reduces precision for BMD comparisons.

Study Details

PMID:21430407
Participants:68
Impact:significantly lower in tamoxifen vs exemestane/anastrozole at 1 and 2 years (p<0.05)
Trust score:3/5

serum collagen N (fibrosis marker)

1 evidences

Randomized study of Qianggan Capsule with or without lamivudine in chronic hepatitis B patients showed marked decreases in serum fibrosis markers (hyaluronic acid, collagen N, laminin) and higher inflammation improvement with combination therapy; fibrosis improvement rates were similar between groups.

Trust comment: Randomized clinical trial reporting biochemical and histologic outcomes, but limited methodological detail and potential reporting limitations.

Study Details

PMID:17186724
Participants:85
Impact:marked decrease after treatment in both groups (p<0.05)
Trust score:3/5

activity of inflammation-necrosis improvement

1 evidences

Randomized study of Qianggan Capsule with or without lamivudine in chronic hepatitis B patients showed marked decreases in serum fibrosis markers (hyaluronic acid, collagen N, laminin) and higher inflammation improvement with combination therapy; fibrosis improvement rates were similar between groups.

Trust comment: Randomized clinical trial reporting biochemical and histologic outcomes, but limited methodological detail and potential reporting limitations.

Study Details

PMID:17186724
Participants:85
Impact:combined therapy 80.0% vs QC alone 57.8% (higher with combination; p<0.05)
Trust score:3/5

fibrosis improvement rate

1 evidences

Randomized study of Qianggan Capsule with or without lamivudine in chronic hepatitis B patients showed marked decreases in serum fibrosis markers (hyaluronic acid, collagen N, laminin) and higher inflammation improvement with combination therapy; fibrosis improvement rates were similar between groups.

Trust comment: Randomized clinical trial reporting biochemical and histologic outcomes, but limited methodological detail and potential reporting limitations.

Study Details

PMID:17186724
Participants:85
Impact:70.0% (combined) vs 75.6% (QC alone); no significant difference
Trust score:3/5

anterior vaginal wall support (1 year)

1 evidences

Reinforcing anterior colporrhaphy with a bovine pericardium (collagen) graft did not result in a statistically significant improvement in anterior vaginal wall support at 1- or 2-year follow-up.

Trust comment: Randomized trial in women directly testing a collagen (bovine pericardium) graft with moderate follow-up and incomplete longer-term retention of participants.

Study Details

PMID:19546759
Participants:72
Impact:85.7% success graft vs 78.4% control (P=0.544) — no significant difference
Trust score:4/5

anterior vaginal wall support (2 years)

1 evidences

Reinforcing anterior colporrhaphy with a bovine pericardium (collagen) graft did not result in a statistically significant improvement in anterior vaginal wall support at 1- or 2-year follow-up.

Trust comment: Randomized trial in women directly testing a collagen (bovine pericardium) graft with moderate follow-up and incomplete longer-term retention of participants.

Study Details

PMID:19546759
Participants:72
Impact:76.5% success graft vs 63% control (P=0.509) — no significant difference
Trust score:4/5

postoperative pain at 1 month

1 evidences

Randomized trial comparing lightweight titanium-coated mesh versus medium-weight collagen-polyester composite mesh found less short-term pain and faster return to activities with the lightweight mesh; recurrence similar at 2 years.

Trust comment: Human randomized controlled trial directly comparing a mesh that contains collagen (collagen-polyester composite); single-center/one-surgeon design limits external generalizability but provides moderate-quality evidence.

Study Details

PMID:22773233
Participants:102
Impact:less common with lightweight titanium-coated mesh (P=0.029)
Trust score:4/5

analgesic consumption (days)

1 evidences

Randomized trial comparing lightweight titanium-coated mesh versus medium-weight collagen-polyester composite mesh found less short-term pain and faster return to activities with the lightweight mesh; recurrence similar at 2 years.

Trust comment: Human randomized controlled trial directly comparing a mesh that contains collagen (collagen-polyester composite); single-center/one-surgeon design limits external generalizability but provides moderate-quality evidence.

Study Details

PMID:22773233
Participants:102
Impact:reported difference: 6.1 d (lightweight) vs 1.6 d (composite) (P<0.001) — as reported in text
Trust score:4/5

return to everyday activities (days)

1 evidences

Randomized trial comparing lightweight titanium-coated mesh versus medium-weight collagen-polyester composite mesh found less short-term pain and faster return to activities with the lightweight mesh; recurrence similar at 2 years.

Trust comment: Human randomized controlled trial directly comparing a mesh that contains collagen (collagen-polyester composite); single-center/one-surgeon design limits external generalizability but provides moderate-quality evidence.

Study Details

PMID:22773233
Participants:102
Impact:earlier with lightweight mesh: 6.9 d vs 9.7 d (P<0.001)
Trust score:4/5

need for skin grafting

1 evidences

In children with partial-thickness burns, collagenase ointment and silver sulfadiazine produced similar clinical outcomes and need for grafting; collagenase had more wound infections (trend) and higher product cost.

Trust comment: Prospective randomized pediatric trial directly evaluating a collagenase product; moderate sample size and randomized design support reasonable trustworthiness.

Study Details

PMID:22703794
Participants:100
Impact:no difference between collagenase ointment and SSD
Trust score:4/5

product cost

1 evidences

In children with partial-thickness burns, collagenase ointment and silver sulfadiazine produced similar clinical outcomes and need for grafting; collagenase had more wound infections (trend) and higher product cost.

Trust comment: Prospective randomized pediatric trial directly evaluating a collagenase product; moderate sample size and randomized design support reasonable trustworthiness.

Study Details

PMID:22703794
Participants:100
Impact:collagenase ointment more expensive (P<0.001); total hospital charges similar
Trust score:4/5

incidence of postoperative air-leak

1 evidences

Pilot randomized trial in COPD patients showed that adding a collagen patch (TachoSil) during upper lobectomy reduced postoperative air-leak, chest-drain duration, and hospital stay versus standard stapling.

Trust comment: Randomized pilot human trial showing clinically significant reductions with a collagen-containing sealant; small sample size limits certainty but methods reported adequately.

Study Details

PMID:19776082
Participants:60
Impact:reduced: 55% (collagen patch) vs 96% (standard) (P=0.03)
Trust score:4/5

mean postoperative air-leak duration (days)

1 evidences

Pilot randomized trial in COPD patients showed that adding a collagen patch (TachoSil) during upper lobectomy reduced postoperative air-leak, chest-drain duration, and hospital stay versus standard stapling.

Trust comment: Randomized pilot human trial showing clinically significant reductions with a collagen-containing sealant; small sample size limits certainty but methods reported adequately.

Study Details

PMID:19776082
Participants:60
Impact:reduced: 1.63 vs 4.33 days (P=0.0018)
Trust score:4/5

chest-drain duration (days)

1 evidences

Pilot randomized trial in COPD patients showed that adding a collagen patch (TachoSil) during upper lobectomy reduced postoperative air-leak, chest-drain duration, and hospital stay versus standard stapling.

Trust comment: Randomized pilot human trial showing clinically significant reductions with a collagen-containing sealant; small sample size limits certainty but methods reported adequately.

Study Details

PMID:19776082
Participants:60
Impact:reduced: 3.53 vs 5.90 days (P=0.0021)
Trust score:4/5

bone-to-implant contact (%BIC)

1 evidences

Three lateral sinus-elevation procedures (including use of a collagen membrane) produced similar new bone formation by micro-CT at 7 months.

Trust comment: Prospective randomized clinical study with objective micro-CT outcomes but small sample size limits generalizability.

Study Details

PMID:23527363
Participants:24
Impact:BW 93.5%, CM 92.0%, ABG 93.5% (no significant between-group differences)
Trust score:4/5

apicobuccal/apicolingual distances

1 evidences

Three lateral sinus-elevation procedures (including use of a collagen membrane) produced similar new bone formation by micro-CT at 7 months.

Trust comment: Prospective randomized clinical study with objective micro-CT outcomes but small sample size limits generalizability.

Study Details

PMID:23527363
Participants:24
Impact:means BW 0.6/1.2 mm, CM 0.5/0.8 mm, ABG 0.6/0.8 mm (within-implant difference, P=0.003)
Trust score:4/5

lateral sinus wall ossification

1 evidences

Three lateral sinus-elevation procedures (including use of a collagen membrane) produced similar new bone formation by micro-CT at 7 months.

Trust comment: Prospective randomized clinical study with objective micro-CT outcomes but small sample size limits generalizability.

Study Details

PMID:23527363
Participants:24
Impact:ABG all ossified; BW 1 incomplete; CM 2 incomplete
Trust score:4/5

VISA score (function)

1 evidences

Injection of autologous skin-derived collagen-producing fibroblasts improved pain and function in refractory Achilles tendinosis at six months.

Trust comment: Randomized double-blind human study but small sample and short follow-up; intervention is cell therapy (collagen-producing cells), not oral collagen supplement.

Study Details

PMID:22241604
Participants:32
Impact:increase (significant at 6 months, p<0.001)
Trust score:3/5

intact PTH (iPTH) / whole PTH (wPTH)

1 evidences

In hemodialysis patients with SHPT, both vitamin D analogs lowered PTH similarly; 22-oxacalcitriol also decreased several bone metabolic markers including collagen-related markers.

Trust comment: Randomized crossover trial in humans with objective biochemical endpoints but small sample and short treatment periods limit conclusions.

Study Details

PMID:17498002
Participants:23
Impact:decrease (similar degree with both treatments)
Trust score:3/5

cross-linked N-telopeptide of type I collagen

1 evidences

In hemodialysis patients with SHPT, both vitamin D analogs lowered PTH similarly; 22-oxacalcitriol also decreased several bone metabolic markers including collagen-related markers.

Trust comment: Randomized crossover trial in humans with objective biochemical endpoints but small sample and short treatment periods limit conclusions.

Study Details

PMID:17498002
Participants:23
Impact:decrease (significant with 22-oxacalcitriol over 12 weeks)
Trust score:3/5

bone-specific alkaline phosphatase / osteocalcin

1 evidences

In hemodialysis patients with SHPT, both vitamin D analogs lowered PTH similarly; 22-oxacalcitriol also decreased several bone metabolic markers including collagen-related markers.

Trust comment: Randomized crossover trial in humans with objective biochemical endpoints but small sample and short treatment periods limit conclusions.

Study Details

PMID:17498002
Participants:23
Impact:decrease (significant with 22-oxacalcitriol)
Trust score:3/5

wounds healed at 8 weeks

1 evidences

Randomized trial in ischemic foot wounds showed a collagen-based tissue-engineered skin graft substantially improved and accelerated wound healing versus moist dressings.

Trust comment: Randomized human trial of a collagen-containing (type I bovine collagen matrix) graft with clear clinical endpoints and significant effects, though sample size is small.

Study Details

PMID:10629263
Participants:31
Impact:Graft 62% vs moist dressing 0% healed at 8 weeks (significant)
Trust score:4/5

wounds healed at 12 weeks

1 evidences

Randomized trial in ischemic foot wounds showed a collagen-based tissue-engineered skin graft substantially improved and accelerated wound healing versus moist dressings.

Trust comment: Randomized human trial of a collagen-containing (type I bovine collagen matrix) graft with clear clinical endpoints and significant effects, though sample size is small.

Study Details

PMID:10629263
Participants:31
Impact:Graft 86% vs moist dressing 40% healed at 12 weeks (p < 0.05)
Trust score:4/5

abdominal circumference

1 evidences

LED photobiomodulation (with or without dermocosmetic) reduced abdominal fat measurements and increased collagen/fibroblast deposition in treated abdominal tissue.

Trust comment: Randomized trial of 90 women with blinded evaluator and multiple objective measures; outcomes statistically significant though magnitude details often not fully numeric.

Study Details

PMID:39645651
Participants:90
Impact:decrease vs sham (LG and LDG; LG showed greater reduction vs LDG; p≤0.02)
Trust score:4/5

adipose layer thickness (ultrasound)

1 evidences

LED photobiomodulation (with or without dermocosmetic) reduced abdominal fat measurements and increased collagen/fibroblast deposition in treated abdominal tissue.

Trust comment: Randomized trial of 90 women with blinded evaluator and multiple objective measures; outcomes statistically significant though magnitude details often not fully numeric.

Study Details

PMID:39645651
Participants:90
Impact:decrease vs sham (LG and LDG; regional differences with LG sometimes > LDG)
Trust score:4/5

collagen deposition (histology)

1 evidences

LED photobiomodulation (with or without dermocosmetic) reduced abdominal fat measurements and increased collagen/fibroblast deposition in treated abdominal tissue.

Trust comment: Randomized trial of 90 women with blinded evaluator and multiple objective measures; outcomes statistically significant though magnitude details often not fully numeric.

Study Details

PMID:39645651
Participants:90
Impact:increase in collagen fibers and fibroblasts in LG vs sham (LDG increased but less than LG)
Trust score:4/5

wound healing duration

1 evidences

Topical PRP gel after pilonidal sinus surgery markedly shortened wound-healing time and time to return to activities, and reduced pain and antibiotic use.

Trust comment: Randomized controlled trial with 110 patients and clear, clinically relevant outcome differences; methods appear appropriate though single-center.

Study Details

PMID:28119114
Participants:110
Impact:decrease: 4.78 ± 0.87 weeks (PRP) vs 8.69 ± 1.18 weeks (control), P=0.03
Trust score:4/5

time to return to routine activities

1 evidences

Topical PRP gel after pilonidal sinus surgery markedly shortened wound-healing time and time to return to activities, and reduced pain and antibiotic use.

Trust comment: Randomized controlled trial with 110 patients and clear, clinically relevant outcome differences; methods appear appropriate though single-center.

Study Details

PMID:28119114
Participants:110
Impact:decrease: 3.3 ± 0.64 weeks (PRP) vs 6.5 ± 1.03 weeks (control), P=0.00
Trust score:4/5

pain and antibiotic duration

1 evidences

Topical PRP gel after pilonidal sinus surgery markedly shortened wound-healing time and time to return to activities, and reduced pain and antibiotic use.

Trust comment: Randomized controlled trial with 110 patients and clear, clinically relevant outcome differences; methods appear appropriate though single-center.

Study Details

PMID:28119114
Participants:110
Impact:reduced in PRP group (P=0.00)
Trust score:4/5

serum β-CTX (baseline)

1 evidences

Among 639 postmenopausal Chinese women, a GGPPS SNP (rs10925503) was associated with baseline serum β-CTX (a collagen breakdown marker) but GGPPS polymorphisms did not affect bone mineral density or biochemical response to alendronate.

Trust comment: Large sample with genotyping and measured biochemical markers; well-powered for association analyses though population-specific.

Study Details

PMID:28031082
Participants:639
Impact:higher in TT genotype vs TC/CC (P<0.05)
Trust score:4/5

response to alendronate (BMD, β-CTX, ALP)

1 evidences

Among 639 postmenopausal Chinese women, a GGPPS SNP (rs10925503) was associated with baseline serum β-CTX (a collagen breakdown marker) but GGPPS polymorphisms did not affect bone mineral density or biochemical response to alendronate.

Trust comment: Large sample with genotyping and measured biochemical markers; well-powered for association analyses though population-specific.

Study Details

PMID:28031082
Participants:639
Impact:no significant difference across GGPPS genotypes (P>0.05)
Trust score:4/5

Neck Disability Index (NDI)

1 evidences

IV zoledronic acid after ACDF shortened time to osteogenesis, promoted fusion, lowered a collagen degradation marker (CTX) and increased lumbar spine BMD, with improved neck disability scores.

Trust comment: Randomized controlled human study with objective biochemical and BMD outcomes but moderate single-center sample size.

Study Details

PMID:31079567
Participants:43
Impact:decreased after surgery in both groups; lower in ZA group at 12 months (significant)
Trust score:4/5

Buccolingual ridge width

1 evidences

Adding i-PRF to autogenous demineralized dentin graft did not change alveolar ridge width loss but reduced patient-reported pain and better preserved keratinized tissue at 6 months.

Trust comment: Randomized clinical trial with objective radiographic and histologic outcomes; modest sample size and partial blinding.

Study Details

PMID:39429193
Participants:22
Impact:reduced in both groups with no significant difference between groups
Trust score:4/5

Skin aging clinical parameters (hydration/elasticity/roughness/wrinkle volume)

1 evidences

Eight weeks of split-face home device use improved skin-aging measures and increased type I collagen expression while decreasing MMP-1, with no adverse effects.

Trust comment: Randomized split-face clinical trial with supportive ex vivo and histology data, moderate sample size and objective endpoints.

Study Details

PMID:38236440
Participants:36
Impact:significant improvements after 8 weeks vs baseline and control side
Trust score:4/5

CTX (C-terminal telopeptide of type 1 collagen)

1 evidences

12-week randomized dietary supplement trial in adults with abdominal obesity; whey protein increased urinary calcium but did not change bone turnover markers or BMD.

Trust comment: Randomized controlled intervention with objective biochemical measures and reasonable sample size, but post-hoc analysis and limited duration.

Study Details

PMID:35422766
Participants:64
Impact:no significant change after 12 weeks
Trust score:4/5

clinical asthma indices

1 evidences

Salmeterol improved clinical asthma measures but did not change airway inflammation or collagen deposition in biopsies after 6 weeks.

Trust comment: Double-blind randomized study in 26 patients; small sample and short duration but direct biopsy and lavage measurements reported.

Study Details

PMID:10515401
Participants:26
Impact:improved with salmeterol (no numeric change reported)
Trust score:3/5

sub-basement membrane collagen deposition

1 evidences

Salmeterol improved clinical asthma measures but did not change airway inflammation or collagen deposition in biopsies after 6 weeks.

Trust comment: Double-blind randomized study in 26 patients; small sample and short duration but direct biopsy and lavage measurements reported.

Study Details

PMID:10515401
Participants:26
Impact:no change in biopsy specimens after 6 weeks
Trust score:3/5

BAL cell counts/mediator levels

1 evidences

Salmeterol improved clinical asthma measures but did not change airway inflammation or collagen deposition in biopsies after 6 weeks.

Trust comment: Double-blind randomized study in 26 patients; small sample and short duration but direct biopsy and lavage measurements reported.

Study Details

PMID:10515401
Participants:26
Impact:no change after treatment
Trust score:3/5

bone turnover markers (osteocalcin, procollagen I peptide, cross-linked telopeptide)

1 evidences

Adults with GH deficiency had reduced BMD in some subgroups; GH replacement increased bone turnover over 12 months.

Trust comment: Moderate-size clinical study with objective BMD and biochemical markers; randomized short blind phase then open-label continuation—reasonable quality though some open-label data.

Study Details

PMID:7655642
Participants:64
Impact:increased during 12 months of GH substitution therapy
Trust score:3/5

immediate complete hemostasis

1 evidences

Using a collagen-based closure device immediately after PTCA was effective and safe; shortening deployment time from 30 to 5 minutes did not increase complications.

Trust comment: Prospective, randomized trial with 140 patients and clinically relevant endpoints; clear safety/efficacy reporting for a collagen-based device.

Study Details

PMID:9258477
Participants:140
Impact:74% (DT-5) vs 71% (DT-30) achieved immediate complete hemostasis
Trust score:4/5

hematoma size at 24 hr

1 evidences

Using a collagen-based closure device immediately after PTCA was effective and safe; shortening deployment time from 30 to 5 minutes did not increase complications.

Trust comment: Prospective, randomized trial with 140 patients and clinically relevant endpoints; clear safety/efficacy reporting for a collagen-based device.

Study Details

PMID:9258477
Participants:140
Impact:6.2 ± 4.4 cm² (DT-5) vs 6.8 ± 8.2 cm² (DT-30); no significant difference
Trust score:4/5

major bleeding/vascular complications

1 evidences

Using a collagen-based closure device immediately after PTCA was effective and safe; shortening deployment time from 30 to 5 minutes did not increase complications.

Trust comment: Prospective, randomized trial with 140 patients and clinically relevant endpoints; clear safety/efficacy reporting for a collagen-based device.

Study Details

PMID:9258477
Participants:140
Impact:no severe bleeding or major complications observed in either group
Trust score:4/5

serum osteocalcin (osteoblast activity)

1 evidences

Propranolol reduced an osteoblast marker (osteocalcin) and modestly reduced a bone resorption marker (urinary deoxypyridinoline) without changing bone density over 3 months.

Trust comment: Randomized, placebo-controlled trial in 41 women with clear biomarker changes; short duration limits BMD conclusions.

Study Details

PMID:15998769
Participants:41
Impact:−~20% within first 2 weeks and remained lower (P < 0.0001)
Trust score:4/5

urine free deoxypyridinoline (bone resorption)

1 evidences

Propranolol reduced an osteoblast marker (osteocalcin) and modestly reduced a bone resorption marker (urinary deoxypyridinoline) without changing bone density over 3 months.

Trust comment: Randomized, placebo-controlled trial in 41 women with clear biomarker changes; short duration limits BMD conclusions.

Study Details

PMID:15998769
Participants:41
Impact:−~10% between 0 and 6 weeks (P = 0.019)
Trust score:4/5

bone mineral density (lumbar spine, proximal femur)

1 evidences

Propranolol reduced an osteoblast marker (osteocalcin) and modestly reduced a bone resorption marker (urinary deoxypyridinoline) without changing bone density over 3 months.

Trust comment: Randomized, placebo-controlled trial in 41 women with clear biomarker changes; short duration limits BMD conclusions.

Study Details

PMID:15998769
Participants:41
Impact:no significant change over 3 months
Trust score:4/5

Fibrosis stage (≥1-stage reduction)

1 evidences

A 24-week randomized phase 2 trial (n=72) found selonsertib-treated patients had higher rates of fibrosis improvement and reductions in hepatic collagen content versus simtuzumab alone.

Trust comment: Multicenter randomized phase 2 trial with blinded central histology/imaging and consistent collagen-related endpoints, but relatively small and open-label for treatment assignment.

Study Details

PMID:28892558
Participants:72
Impact:18 mg selonsertib: 13/30 (43%); 6 mg: 8/27 (30%); simtuzumab alone: 2/10 (20%)
Trust score:4/5

MRI-PDFF (hepatic fat)

1 evidences

A 24-week randomized phase 2 trial (n=72) found selonsertib-treated patients had higher rates of fibrosis improvement and reductions in hepatic collagen content versus simtuzumab alone.

Trust comment: Multicenter randomized phase 2 trial with blinded central histology/imaging and consistent collagen-related endpoints, but relatively small and open-label for treatment assignment.

Study Details

PMID:28892558
Participants:72
Impact:median % change: −4.55% (18 mg), −6.67% (6 mg), −12.72% (simtuzumab)
Trust score:4/5

PICP/CITP ratio (collagen turnover)

1 evidences

Among older adults at risk for heart failure, diabetes was associated with altered collagen biomarkers and diastolic function; spironolactone had modest short-term effects on collagen turnover markers but no major differential long-term effects by diabetes/CAD status.

Trust comment: Randomized, multicentre trial with validated biomarker assays and moderate sample size; post-hoc subgroup analysis limits causal inferences.

Study Details

PMID:40057728
Participants:495
Impact:↓ (Exp(β)=0.867 for DM+/CAD- vs reference, p=0.011); spironolactone 1‑month mdiff −2.95 (95% CI −4.73 to −1.17), p<0.001
Trust score:4/5

E/e′ ratio (marker of LV filling pressure)

1 evidences

Among older adults at risk for heart failure, diabetes was associated with altered collagen biomarkers and diastolic function; spironolactone had modest short-term effects on collagen turnover markers but no major differential long-term effects by diabetes/CAD status.

Trust comment: Randomized, multicentre trial with validated biomarker assays and moderate sample size; post-hoc subgroup analysis limits causal inferences.

Study Details

PMID:40057728
Participants:495
Impact:+1.355 (DM+/CAD- vs DM-/CAD+, adjusted beta), p=0.003
Trust score:4/5

resorbed area on bone slices (osteoclast activity)

1 evidences

In this double-blind, placebo-controlled cross-over trial subgroup, radon spa treatment reduced osteoclast activity and RANKL and increased regulatory T cells versus baseline, suggesting reduced bone resorption; some systemic collagen fragment (CTX) measures were unchanged.

Trust comment: Prospective, double-blind, placebo-controlled cross-over trial with objective ex vivo and serum measures; subgroup analyses and cohort heterogeneity limit full generalizability but methods are rigorous.

Study Details

PMID:38292488
Participants:58
Impact:reduced ~5-fold at 24 weeks after radon spa treatment (approx. -80%)
Trust score:4/5

RANKL concentration

1 evidences

In this double-blind, placebo-controlled cross-over trial subgroup, radon spa treatment reduced osteoclast activity and RANKL and increased regulatory T cells versus baseline, suggesting reduced bone resorption; some systemic collagen fragment (CTX) measures were unchanged.

Trust comment: Prospective, double-blind, placebo-controlled cross-over trial with objective ex vivo and serum measures; subgroup analyses and cohort heterogeneity limit full generalizability but methods are rigorous.

Study Details

PMID:38292488
Participants:58
Impact:significant decrease after radon treatment (noted at 24 weeks)
Trust score:4/5

Treg fraction / Th17/Treg ratio

1 evidences

In this double-blind, placebo-controlled cross-over trial subgroup, radon spa treatment reduced osteoclast activity and RANKL and increased regulatory T cells versus baseline, suggesting reduced bone resorption; some systemic collagen fragment (CTX) measures were unchanged.

Trust comment: Prospective, double-blind, placebo-controlled cross-over trial with objective ex vivo and serum measures; subgroup analyses and cohort heterogeneity limit full generalizability but methods are rigorous.

Study Details

PMID:38292488
Participants:58
Impact:Treg fraction increased ~1.5-fold at 12 weeks; Th17/Treg ratio decreased (significant)
Trust score:4/5

Graft patency / success rate (healthy urethral bed)

1 evidences

Acellular bladder (collagen-based) matrix grafts worked well in patients with a healthy urethral bed but performed worse than buccal mucosa in patients with an unhealthy bed; both groups showed improved urine flow.

Trust comment: -Checklist: confirm direct collagen intervention; list top outcomes (graft patency, uroflowmetry, histology); assign trust score.-Justification: This randomized clinical study directly evaluates a collagen-based acellular bladder matrix in humans; randomized design but small sample and some loss to follow-up reduce confidence, so rated 3.

Study Details

PMID:18295282
Participants:28
Impact:buccal mucosa 10/10 (100%) vs bladder matrix 8/9 (~89%)
Trust score:3/5

Graft patency / success rate (unhealthy urethral bed)

1 evidences

Acellular bladder (collagen-based) matrix grafts worked well in patients with a healthy urethral bed but performed worse than buccal mucosa in patients with an unhealthy bed; both groups showed improved urine flow.

Trust comment: -Checklist: confirm direct collagen intervention; list top outcomes (graft patency, uroflowmetry, histology); assign trust score.-Justification: This randomized clinical study directly evaluates a collagen-based acellular bladder matrix in humans; randomized design but small sample and some loss to follow-up reduce confidence, so rated 3.

Study Details

PMID:18295282
Participants:28
Impact:buccal mucosa 5/5 (100%) vs bladder matrix 2/6 (~33%)
Trust score:3/5

Uroflowmetry (voiding improvement)

1 evidences

Acellular bladder (collagen-based) matrix grafts worked well in patients with a healthy urethral bed but performed worse than buccal mucosa in patients with an unhealthy bed; both groups showed improved urine flow.

Trust comment: -Checklist: confirm direct collagen intervention; list top outcomes (graft patency, uroflowmetry, histology); assign trust score.-Justification: This randomized clinical study directly evaluates a collagen-based acellular bladder matrix in humans; randomized design but small sample and some loss to follow-up reduce confidence, so rated 3.

Study Details

PMID:18295282
Participants:28
Impact:significant improvement in both groups (no percent reported)
Trust score:3/5

incidence of postoperative air leakage at ~48 h

1 evidences

A collagen-coated patch (TachoComb) was safe and, in patients with mild–moderate intra-operative leaks, reduced leak intensity and shortened postoperative leak duration compared with standard treatment.

Trust comment: Multicenter randomized prospective study with objective leak measurements and clear subgroup benefits; effect mainly shown in patients with grades 1–2 leaks.

Study Details

PMID:14747106
Participants:189
Impact:no significant change (34% TC vs 37% control, P=0.76)
Trust score:4/5

intra-operative air leak intensity (grades 1–2)

1 evidences

A collagen-coated patch (TachoComb) was safe and, in patients with mild–moderate intra-operative leaks, reduced leak intensity and shortened postoperative leak duration compared with standard treatment.

Trust comment: Multicenter randomized prospective study with objective leak measurements and clear subgroup benefits; effect mainly shown in patients with grades 1–2 leaks.

Study Details

PMID:14747106
Participants:189
Impact:reduced with collagen patch (significant, P=0.015)
Trust score:4/5

duration of postoperative air leakage (grades 1–2)

1 evidences

A collagen-coated patch (TachoComb) was safe and, in patients with mild–moderate intra-operative leaks, reduced leak intensity and shortened postoperative leak duration compared with standard treatment.

Trust comment: Multicenter randomized prospective study with objective leak measurements and clear subgroup benefits; effect mainly shown in patients with grades 1–2 leaks.

Study Details

PMID:14747106
Participants:189
Impact:reduced by 0.8 days (1.9±1.4 vs 2.7±2.2 d, P=0.015)
Trust score:4/5

postoperative air leakage intensity (grades 1–2)

1 evidences

A collagen-coated patch (TachoComb) was safe and, in patients with mild–moderate intra-operative leaks, reduced leak intensity and shortened postoperative leak duration compared with standard treatment.

Trust comment: Multicenter randomized prospective study with objective leak measurements and clear subgroup benefits; effect mainly shown in patients with grades 1–2 leaks.

Study Details

PMID:14747106
Participants:189
Impact:lower with collagen patch (significant, P=0.047)
Trust score:4/5

Sum of pain intensity over 24 h (SPI24)

1 evidences

Phase III randomized, double‑blind trial of a bovine type I collagen matrix implant (INL‑001) delivering bupivacaine versus placebo collagen matrix in abdominoplasty patients assessing postoperative pain and opioid use.

Trust comment: Large, multicenter, randomized double‑blind placebo‑controlled phase III trial evaluating a collagen‑matrix implant with clear prespecified endpoints and registration; high-quality evidence for this intervention.

Study Details

PMID:37076252
Participants:337
Impact:INL‑001 lower than placebo (mean 102.1 vs 117.0); LS mean difference −14.8; p=0.002
Trust score:5/5

Opioid‑free at 24 h

1 evidences

Phase III randomized, double‑blind trial of a bovine type I collagen matrix implant (INL‑001) delivering bupivacaine versus placebo collagen matrix in abdominoplasty patients assessing postoperative pain and opioid use.

Trust comment: Large, multicenter, randomized double‑blind placebo‑controlled phase III trial evaluating a collagen‑matrix implant with clear prespecified endpoints and registration; high-quality evidence for this intervention.

Study Details

PMID:37076252
Participants:337
Impact:INL‑001 18.8% vs placebo 6.5% (difference ~+12.3 percentage points)
Trust score:5/5

SPI48

1 evidences

Phase III randomized, double‑blind trial of a bovine type I collagen matrix implant (INL‑001) delivering bupivacaine versus placebo collagen matrix in abdominoplasty patients assessing postoperative pain and opioid use.

Trust comment: Large, multicenter, randomized double‑blind placebo‑controlled phase III trial evaluating a collagen‑matrix implant with clear prespecified endpoints and registration; high-quality evidence for this intervention.

Study Details

PMID:37076252
Participants:337
Impact:numeric reduction (190.4 vs 205.8) but not statistically significant (p=0.12)
Trust score:5/5

sinus floor level change

1 evidences

Using a collagenated bovine bone and resorbable collagen membrane after upper back tooth extraction preserved vertical bone height better than no grafting over 6 months.

Trust comment: Randomized controlled trial with clear radiographic outcomes but small sample size.

Study Details

PMID:30980771
Participants:40
Impact:Test: -0.14 mm (baseline→6 mo) vs Control: -1.16 mm (baseline→6 mo); less coronal shift in test
Trust score:4/5

residual bone height

1 evidences

Using a collagenated bovine bone and resorbable collagen membrane after upper back tooth extraction preserved vertical bone height better than no grafting over 6 months.

Trust comment: Randomized controlled trial with clear radiographic outcomes but small sample size.

Study Details

PMID:30980771
Participants:40
Impact:Test 7.30 mm vs Control 4.83 mm at 6 months
Trust score:4/5

need for sinus augmentation

1 evidences

Using a collagenated bovine bone and resorbable collagen membrane after upper back tooth extraction preserved vertical bone height better than no grafting over 6 months.

Trust comment: Randomized controlled trial with clear radiographic outcomes but small sample size.

Study Details

PMID:30980771
Participants:40
Impact:Implant without augmentation possible in 42.9% test vs 0% control (100% needed augmentation)
Trust score:4/5

gastrointestinal/intestinal fistula incidence

1 evidences

A collagen-containing fibrinogen/thrombin sponge applied to gastrointestinal sutures reduced anastomotic leaks in high-risk oncology patients.

Trust comment: Prospective comparative study with randomization for anastomoses subgroup but small sample for the reinforced-anastomosis comparison (49 anastomoses), limiting precision.

Study Details

PMID:26776435
Participants:73
Impact:−6.1% (3/49 in control → 0/22 in sponge group)
Trust score:3/5

ridge width loss

1 evidences

Using a collagenated bovine bone mineral and a resorbable collagen membrane for ridge preservation reduced post-extraction ridge shrinkage and volumetric loss compared with spontaneous healing.

Trust comment: Randomized controlled trial directly using collagen-containing materials but small sample (n=26) which limits generalizability despite clear imaging and histologic endpoints.

Study Details

PMID:33316099
Participants:26
Impact:Reduced with ridge preservation: difference −3.3 mm at 1 mm below crest and −2.2 mm at 3 mm below crest (p<0.05)
Trust score:3/5

socket height change

1 evidences

Using a collagenated bovine bone mineral and a resorbable collagen membrane for ridge preservation reduced post-extraction ridge shrinkage and volumetric loss compared with spontaneous healing.

Trust comment: Randomized controlled trial directly using collagen-containing materials but small sample (n=26) which limits generalizability despite clear imaging and histologic endpoints.

Study Details

PMID:33316099
Participants:26
Impact:RP +0.25 mm vs SH −0.39 mm (p<0.05)
Trust score:3/5

flow-mediated vasodilatation

1 evidences

Terutroban improved endothelial function and blocked TP receptor–mediated platelet aggregation in high-cardiovascular-risk patients on aspirin.

Trust comment: Randomized double-blind placebo-controlled trial but modest sample size (n=48).

Study Details

PMID:21564160
Participants:48
Impact:improved (after single dose and after 14 days)
Trust score:4/5

TP-induced platelet aggregation

1 evidences

Terutroban improved endothelial function and blocked TP receptor–mediated platelet aggregation in high-cardiovascular-risk patients on aspirin.

Trust comment: Randomized double-blind placebo-controlled trial but modest sample size (n=48).

Study Details

PMID:21564160
Participants:48
Impact:abolished (U46619-induced aggregation)
Trust score:4/5

femoral neck BMC

1 evidences

Progressive high-impact exercise increased bone mass and improved balance and muscle function but did not change MRI-estimated cartilage biochemical composition in postmenopausal women.

Trust comment: 12-month randomized controlled trial with objective DXA and MRI measures and moderate completed sample size.

Study Details

PMID:23775755
Participants:76
Impact:+0.6% (exercise) vs -1.2% (control)
Trust score:4/5

cartilage biochemical composition (dGEMRIC/T2)

1 evidences

Progressive high-impact exercise increased bone mass and improved balance and muscle function but did not change MRI-estimated cartilage biochemical composition in postmenopausal women.

Trust comment: 12-month randomized controlled trial with objective DXA and MRI measures and moderate completed sample size.

Study Details

PMID:23775755
Participants:76
Impact:no change
Trust score:4/5

balance and muscle/fitness measures

1 evidences

Progressive high-impact exercise increased bone mass and improved balance and muscle function but did not change MRI-estimated cartilage biochemical composition in postmenopausal women.

Trust comment: 12-month randomized controlled trial with objective DXA and MRI measures and moderate completed sample size.

Study Details

PMID:23775755
Participants:76
Impact:improved by 3%–11% (exercise vs control)
Trust score:4/5

pain-related quality of life

1 evidences

Alendronate reduced pain and improved pain-related quality of life and increased lumbar BMD more than alfacalcidol in postmenopausal osteoporotic women.

Trust comment: Randomized comparative crossover but open-label and small sample, limiting robustness.

Study Details

PMID:20458350
Participants:34
Impact:improved (alendronate)
Trust score:3/5

major trochanter BMD

1 evidences

Alendronate prevented glucocorticoid-induced bone loss, increasing BMD at spine and hip sites over 24 weeks compared with calcium alone.

Trust comment: Randomized trial with substantial sample size and clear BMD improvements at multiple sites.

Study Details

PMID:19040000
Participants:140
Impact:+3.3% (24 weeks vs baseline)
Trust score:4/5

serum type-1 collagen C-telopeptide (CTx)

1 evidences

Daily high-calcium mineral water (596 mg Ca) for 6 months lowered PTH and multiple bone turnover markers; adding 400 IU vitamin D provided no additional reduction.

Trust comment: Randomized double-blind placebo-controlled trial with large completed sample and objective biochemical endpoints.

Study Details

PMID:15744450
Participants:152
Impact:-16.3% (HCaMW vs placebo)
Trust score:4/5

sensitivity reactions

1 evidences

Compared replacement formulas; the formula containing hydrolysed soya plus bovine collagen had fewer sensitivity reactions and similar time to tolerance.

Trust comment: Randomized 24-month follow-up but small sample (n=55); directly includes bovine collagen in one formula arm.

Study Details

PMID:8766671
Participants:55
Impact:8% in hydrolysate soy + bovine collagen group (vs 22% soy; 37.5% casein)
Trust score:3/5

time to acquire clinical tolerance

1 evidences

Compared replacement formulas; the formula containing hydrolysed soya plus bovine collagen had fewer sensitivity reactions and similar time to tolerance.

Trust comment: Randomized 24-month follow-up but small sample (n=55); directly includes bovine collagen in one formula arm.

Study Details

PMID:8766671
Participants:55
Impact:mean 11.6 ± 6.02 months (group with hydrolysate soy + bovine collagen)
Trust score:3/5

Glyaderm take rate

1 evidences

Glyaderm (acellular dermis composed of collagen) showed good graft take and improved scar elasticity/quality versus STSG alone.

Trust comment: Phase III randomized, paired intra-individual trial directly testing a collagen-based dermal substitute (moderate sample size); results clinically relevant though sample is modest.

Study Details

PMID:24946965
Participants:55
Impact:88.17% mean take rate in randomized trial (pilot mean 91.55%)
Trust score:4/5

scar elasticity/quality at 1 year

1 evidences

Glyaderm (acellular dermis composed of collagen) showed good graft take and improved scar elasticity/quality versus STSG alone.

Trust comment: Phase III randomized, paired intra-individual trial directly testing a collagen-based dermal substitute (moderate sample size); results clinically relevant though sample is modest.

Study Details

PMID:24946965
Participants:55
Impact:improved elasticity (p=0.003) and better blinded scar scores vs STSG alone
Trust score:4/5

C3M (type III collagen degradation)

1 evidences

Biomarker sub-study of an RCT in RA showing tocilizumab reduces collagen-degradation biomarkers and CRP more than methotrexate by week 8.

Trust comment: Large, randomized phase‑3 trial sub-study with validated assays and appropriate statistics, but limited to short (8‑week) biomarker follow‑up.

Study Details

PMID:33413588
Participants:387
Impact:↓ significant with tocilizumab vs placebo; 16% greater reduction vs methotrexate
Trust score:4/5

sCTX (C‑terminal telopeptide of type I collagen)

1 evidences

Monthly oral ibandronate increased lumbar spine and hip BMD and reduced bone turnover markers in postmenopausal women on glucocorticoids; vitamin D and calcium were provided to all.

Trust comment: Well‑conducted 12‑month randomized double‑blind placebo‑controlled trial with clear BMD endpoints and biochemical markers.

Study Details

PMID:22803768
Participants:140
Impact:↓ significantly greater with ibandronate vs placebo at 1, 6 and 12 months
Trust score:4/5

P1NP (N‑terminal propeptide of type I procollagen)

1 evidences

Monthly oral ibandronate increased lumbar spine and hip BMD and reduced bone turnover markers in postmenopausal women on glucocorticoids; vitamin D and calcium were provided to all.

Trust comment: Well‑conducted 12‑month randomized double‑blind placebo‑controlled trial with clear BMD endpoints and biochemical markers.

Study Details

PMID:22803768
Participants:140
Impact:↓ significantly greater with ibandronate vs placebo at 1, 6 and 12 months
Trust score:4/5

Subepithelial collagen‑band thickness

1 evidences

Experimental challenge study in asthma showing repeated bronchoconstriction (with allergen or methacholine) increases subepithelial collagen deposition and mucus changes independent of eosinophilic inflammation.

Trust comment: Randomized challenge protocol with paired biopsies and objective histologic measurements, but small sample size limits generalizability.

Study Details

PMID:21612469
Participants:48
Impact:↑ median +2.17 μm (allergen) and +1.94 μm (methacholine) vs controls (P<0.001)
Trust score:4/5

Periodic acid–Schiff staining (mucus epithelium)

1 evidences

Experimental challenge study in asthma showing repeated bronchoconstriction (with allergen or methacholine) increases subepithelial collagen deposition and mucus changes independent of eosinophilic inflammation.

Trust comment: Randomized challenge protocol with paired biopsies and objective histologic measurements, but small sample size limits generalizability.

Study Details

PMID:21612469
Participants:48
Impact:↑ median +2.17 percentage points (allergen) and +2.13 percentage points (methacholine) vs controls (P=0.003)
Trust score:4/5

Serum C‑telopeptide (type I collagen)

1 evidences

Long‑term extension of ibandronate treatment showing sustained increases in lumbar spine and hip BMD and persistent reductions in type I collagen turnover markers over 3 years.

Trust comment: Large long‑term extension with clinically meaningful BMD and biochemical outcomes; post‑hoc elements and extension design modestly limit causal strength.

Study Details

PMID:18180976
Participants:719
Impact:↓ significantly over 3 years (remained within premenopausal range)
Trust score:4/5

Vertical bone fill (furcation defect)

1 evidences

Clinical study of mandibular Class II furcation defects showing bone graft improves vertical defect fill and that adding a bioabsorbable collagen membrane did not further enhance regeneration.

Trust comment: Small clinical cohort with clear outcome measures showing no added benefit from collagen membrane, but limited sample size reduces precision.

Study Details

PMID:16584345
Participants:27
Impact:Bone graft (BG) markedly increased likelihood of >50% vertical fill vs open flap debridement (BG ~16× more likely); BG also 64× more likely to achieve 1‑mm fill vs OFD
Trust score:3/5

Effect of bioabsorbable collagen membrane added to BG

1 evidences

Clinical study of mandibular Class II furcation defects showing bone graft improves vertical defect fill and that adding a bioabsorbable collagen membrane did not further enhance regeneration.

Trust comment: Small clinical cohort with clear outcome measures showing no added benefit from collagen membrane, but limited sample size reduces precision.

Study Details

PMID:16584345
Participants:27
Impact:No additional regenerative benefit of collagen membrane when added to bone graft (BG + collagen membrane ≈ BG alone)
Trust score:3/5

Pro-C3 (type III procollagen pro-peptide) AUEC

1 evidences

First-in-human randomized placebo-controlled study: bersiporocin lowered the serum collagen synthesis biomarker Pro-C3 and caused mostly mild gastrointestinal adverse events.

Trust comment: Phase I randomized, double-blind placebo-controlled human study showing reduced Pro-C3 (collagen biomarker); small sample sizes and sponsor involvement limit generalizability.

Study Details

PMID:37095713
Participants:72
Impact:decreased after bersiporocin vs placebo (statistically significant after single dose; not significant after multiple doses)
Trust score:4/5

Gastrointestinal adverse events (nausea, diarrhea, vomiting)

1 evidences

First-in-human randomized placebo-controlled study: bersiporocin lowered the serum collagen synthesis biomarker Pro-C3 and caused mostly mild gastrointestinal adverse events.

Trust comment: Phase I randomized, double-blind placebo-controlled human study showing reduced Pro-C3 (collagen biomarker); small sample sizes and sponsor involvement limit generalizability.

Study Details

PMID:37095713
Participants:72
Impact:high incidence (most events mild), increased with dose and more after morning doses
Trust score:4/5

Other PD biomarkers (Pro-C6, C3M, C6M)

1 evidences

First-in-human randomized placebo-controlled study: bersiporocin lowered the serum collagen synthesis biomarker Pro-C3 and caused mostly mild gastrointestinal adverse events.

Trust comment: Phase I randomized, double-blind placebo-controlled human study showing reduced Pro-C3 (collagen biomarker); small sample sizes and sponsor involvement limit generalizability.

Study Details

PMID:37095713
Participants:72
Impact:no apparent trend or significant differences vs placebo
Trust score:4/5

buccal alveolar bone thickness (BT)

1 evidences

In PAOO patients, collagen barrier membrane (control) increased gingival thickness modestly at 6 months, but CGF membrane produced a larger increase; both groups showed bone parameter changes.

Trust comment: Randomized controlled trial directly comparing a collagen barrier membrane (control) to CGF membrane with objective CBCT measures and 6-month follow-up; single-center and modest sample size limit external generalizability.

Study Details

PMID:34814921
Participants:40
Impact:control increased from 1.04±0.48 to 1.43±0.04 mm (significant within-group), no significant difference versus CGF
Trust score:4/5

pain (2-week)

1 evidences

In PAOO patients, collagen barrier membrane (control) increased gingival thickness modestly at 6 months, but CGF membrane produced a larger increase; both groups showed bone parameter changes.

Trust comment: Randomized controlled trial directly comparing a collagen barrier membrane (control) to CGF membrane with objective CBCT measures and 6-month follow-up; single-center and modest sample size limit external generalizability.

Study Details

PMID:34814921
Participants:40
Impact:control had higher early postoperative pain vs CGF (CGF lower pain score at 2 weeks; p=0.024)
Trust score:4/5

Overall composite success (fusion + clinical endpoints)

1 evidences

Pivotal randomized FDA IDE trial comparing i-Factor (P‑15 synthetic collagen fragment bone graft) versus local autograft in single-level anterior cervical fusion with 2-year follow-up; similar clinical outcomes and fusion rates, with a higher composite overall success for i-Factor.

Trust comment: Randomized FDA IDE multicenter trial with large sample and 2-year follow-up; direct test of a collagen-containing device (P-15), but industry/device context noted.

Study Details

PMID:28945914
Participants:319
Impact:69.83% (i-Factor) vs 56.35% (autograft); P=0.0302 (significant)
Trust score:4/5

Neck Disability Index improvement

1 evidences

Pivotal randomized FDA IDE trial comparing i-Factor (P‑15 synthetic collagen fragment bone graft) versus local autograft in single-level anterior cervical fusion with 2-year follow-up; similar clinical outcomes and fusion rates, with a higher composite overall success for i-Factor.

Trust comment: Randomized FDA IDE multicenter trial with large sample and 2-year follow-up; direct test of a collagen-containing device (P-15), but industry/device context noted.

Study Details

PMID:28945914
Participants:319
Impact:28.30 (i-Factor) vs 26.95 (autograft); P=0.1448 (NS)
Trust score:4/5

Initial hemostasis effectiveness (physician VAS)

1 evidences

Floseal, a collagen-derived hemostatic sealant, was more effective, easier to use, better tolerated, and had lower short-term rebleeding rates than nasal packing for anterior epistaxis.

Trust comment: Randomized controlled trial directly testing a collagen-derived medical product with clear, significant clinical outcomes; limited by nonblinded design but otherwise well-conducted.

Study Details

PMID:15867662
Participants:70
Impact:+2.2 points (9.9 vs 7.7, P<.001)
Trust score:4/5

Patient discomfort during hemostasis (VAS)

1 evidences

Floseal, a collagen-derived hemostatic sealant, was more effective, easier to use, better tolerated, and had lower short-term rebleeding rates than nasal packing for anterior epistaxis.

Trust comment: Randomized controlled trial directly testing a collagen-derived medical product with clear, significant clinical outcomes; limited by nonblinded design but otherwise well-conducted.

Study Details

PMID:15867662
Participants:70
Impact:-7.5 points (1.4 vs 8.9, P<.001)
Trust score:4/5

Rebleeding within 7 days

1 evidences

Floseal, a collagen-derived hemostatic sealant, was more effective, easier to use, better tolerated, and had lower short-term rebleeding rates than nasal packing for anterior epistaxis.

Trust comment: Randomized controlled trial directly testing a collagen-derived medical product with clear, significant clinical outcomes; limited by nonblinded design but otherwise well-conducted.

Study Details

PMID:15867662
Participants:70
Impact:-26 percentage points (14% vs 40%, P<.05)
Trust score:4/5

aesthetic score (IAS)

1 evidences

Randomized trial (78 enrolled, 8 excluded/dropouts = 70 completed) comparing internal socket grafting alone versus with additional buccal augmentation covered by collagen resorbable membranes; no significant differences at 6 months.

Trust comment: Multicenter randomized controlled trial with blinded assessors and reported outcomes; modest sample and short-term follow-up but directly uses collagen membranes as part of the intervention.

Study Details

PMID:24179978
Participants:70
Impact:no significant difference; mean 8.0 vs 7.8 (difference 0.2)
Trust score:4/5

Wound epithelialization (5–7 days)

1 evidences

Multicenter randomized trial comparing standard skin grafts vs grafts plus cultured autologous epidermal cells seeded in a collagen carrier; assessed healing and scar quality.

Trust comment: Randomized multicenter trial with clinically relevant endpoints (n=40); intervention combined cultured cells with a collagen carrier so effects cannot be attributed to collagen alone.

Study Details

PMID:26419871
Participants:40
Impact:+4 percentage points (71% vs 67%; P=0.034)
Trust score:3/5

Scar quality (POSAS)

1 evidences

Multicenter randomized trial comparing standard skin grafts vs grafts plus cultured autologous epidermal cells seeded in a collagen carrier; assessed healing and scar quality.

Trust comment: Randomized multicenter trial with clinically relevant endpoints (n=40); intervention combined cultured cells with a collagen carrier so effects cannot be attributed to collagen alone.

Study Details

PMID:26419871
Participants:40
Impact:Improved by 12–23% at 3–12 months (p≤0.01)
Trust score:3/5

vertical buccal crest height loss (3 months)

1 evidences

Grafting extraction sockets with DBBM-C (deproteinized bovine bone mineral with 10% porcine collagen) preserved buccal crest height and ridge width significantly better than no graft over 1 year.

Trust comment: Randomized single-blind clinical trial with imaging-based outcomes showing consistent, significant benefit of a collagen-containing graft; moderate sample size and 3 lost to follow-up.

Study Details

PMID:33840514
Participants:33
Impact:Control mean loss 1.2 ± 1.8 mm vs DBBM-C 0.3 ± 1.2 mm (difference ≈ 0.9 mm less loss; P<.001)
Trust score:4/5

vertical buccal crest height loss (1 year)

1 evidences

Grafting extraction sockets with DBBM-C (deproteinized bovine bone mineral with 10% porcine collagen) preserved buccal crest height and ridge width significantly better than no graft over 1 year.

Trust comment: Randomized single-blind clinical trial with imaging-based outcomes showing consistent, significant benefit of a collagen-containing graft; moderate sample size and 3 lost to follow-up.

Study Details

PMID:33840514
Participants:33
Impact:Control 2.1 ± 2.0 mm vs DBBM-C 0.7 ± 1.4 mm (difference ≈ 1.4 mm less loss; P<.001)
Trust score:4/5

horizontal ridge width change (1 year)

1 evidences

Grafting extraction sockets with DBBM-C (deproteinized bovine bone mineral with 10% porcine collagen) preserved buccal crest height and ridge width significantly better than no graft over 1 year.

Trust comment: Randomized single-blind clinical trial with imaging-based outcomes showing consistent, significant benefit of a collagen-containing graft; moderate sample size and 3 lost to follow-up.

Study Details

PMID:33840514
Participants:33
Impact:Control mean loss 2.2 ± 1.4 mm vs DBBM-C 0.9 ± 1.1 mm (difference ≈ 1.3 mm less loss; P<.001)
Trust score:4/5

rotator cuff retear rate

1 evidences

Injecting patients' own dermal fibroblasts between tendon and bone during rotator cuff repair reduced retear rate but did not change shoulder function scores at 6–12 months.

Trust comment: Prospective randomized controlled trial (Level 2) with an appropriate primary outcome and significant effect on retear rate; moderate sample and some dropouts.

Study Details

PMID:39876067
Participants:73
Impact:-18.7 percentage points (24.3% → 5.6%; control vs ADF)
Trust score:4/5

shoulder function scores (ASES, Constant, SST)

1 evidences

Injecting patients' own dermal fibroblasts between tendon and bone during rotator cuff repair reduced retear rate but did not change shoulder function scores at 6–12 months.

Trust comment: Prospective randomized controlled trial (Level 2) with an appropriate primary outcome and significant effect on retear rate; moderate sample and some dropouts.

Study Details

PMID:39876067
Participants:73
Impact:No significant difference at 6 and 12 months
Trust score:4/5

tissue shrinkage

1 evidences

Acellular dermal matrix (ADM) produced more collagen fibers but showed greater tissue shrinkage and delayed healing compared with free gingival grafts.

Trust comment: Small split‑mouth randomized trial with histology supporting findings but limited sample size and some outcomes lacking numeric detail.

Study Details

PMID:29713889
Participants:25
Impact:+43.29 percentage points (12.41% → 55.7%) for ADM vs FGG
Trust score:3/5

percentage of collagen fibers (histology)

1 evidences

Acellular dermal matrix (ADM) produced more collagen fibers but showed greater tissue shrinkage and delayed healing compared with free gingival grafts.

Trust comment: Small split‑mouth randomized trial with histology supporting findings but limited sample size and some outcomes lacking numeric detail.

Study Details

PMID:29713889
Participants:25
Impact:Higher in ADM sites (no numeric value reported)
Trust score:3/5

graft stem dilation (day 8)

1 evidences

In randomized patients, collagen-sealed warp-knitted polyester grafts showed greater early dilation than gelatin-sealed Köper-knitted grafts at day 8; dilation did not increase further at 3 and 6 months.

Trust comment: Randomized human study directly involving collagen-sealed grafts; small sample size and short follow-up limit generalizability.

Study Details

PMID:10642718
Participants:34
Impact:warp-knitted (collagen-sealed) +27% ±13% vs Köper (gelatin-sealed) +18% ±8%
Trust score:3/5

graft limb dilation (day 8)

1 evidences

In randomized patients, collagen-sealed warp-knitted polyester grafts showed greater early dilation than gelatin-sealed Köper-knitted grafts at day 8; dilation did not increase further at 3 and 6 months.

Trust comment: Randomized human study directly involving collagen-sealed grafts; small sample size and short follow-up limit generalizability.

Study Details

PMID:10642718
Participants:34
Impact:warp-knitted (collagen-sealed) +33% ±18% vs Köper (gelatin-sealed) +15% ±12%
Trust score:3/5

dilation over 3 and 6 months

1 evidences

In randomized patients, collagen-sealed warp-knitted polyester grafts showed greater early dilation than gelatin-sealed Köper-knitted grafts at day 8; dilation did not increase further at 3 and 6 months.

Trust comment: Randomized human study directly involving collagen-sealed grafts; small sample size and short follow-up limit generalizability.

Study Details

PMID:10642718
Participants:34
Impact:no further increase from day 8 values
Trust score:3/5

static two-point discrimination

1 evidences

Multicenter randomized trial comparing collagen conduit versus processed nerve allograft (PNA) for digital nerve repair: similar results for short gaps but collagen conduits were inferior for long-gap repairs.

Trust comment: Large multicenter randomized, blinded trial with substantial completers and objective sensory endpoints; high-quality evidence for collagen conduit in this surgical indication.

Study Details

PMID:37530686
Participants:183
Impact:Long gaps: PNA 6.1 mm vs collagen conduit 7.5 mm (collagen worse by ≈+1.4 mm)
Trust score:4/5

normal sensation rate (ASSH scale)

1 evidences

Multicenter randomized trial comparing collagen conduit versus processed nerve allograft (PNA) for digital nerve repair: similar results for short gaps but collagen conduits were inferior for long-gap repairs.

Trust comment: Large multicenter randomized, blinded trial with substantial completers and objective sensory endpoints; high-quality evidence for collagen conduit in this surgical indication.

Study Details

PMID:37530686
Participants:183
Impact:Long gaps: collagen 18% vs PNA 40% (≈-22 percentage points for collagen)
Trust score:4/5

clinical failure (lack of protective sensation)

1 evidences

Multicenter randomized trial comparing collagen conduit versus processed nerve allograft (PNA) for digital nerve repair: similar results for short gaps but collagen conduits were inferior for long-gap repairs.

Trust comment: Large multicenter randomized, blinded trial with substantial completers and objective sensory endpoints; high-quality evidence for collagen conduit in this surgical indication.

Study Details

PMID:37530686
Participants:183
Impact:Long-gap conduits had higher clinical failure rate vs short-gap conduits (more failures with collagen conduits)
Trust score:4/5

L1–L4 BMD

1 evidences

Randomized double-blind trial in thalassemia patients: weekly alendronate for 12 months increased lumbar (L1–L4) BMD and reduced bone turnover markers versus placebo.

Trust comment: Double-blind randomized controlled design with predefined endpoints and measured biomarkers; modest sample size but well-conducted.

Study Details

PMID:37251676
Participants:47
Impact:+4.95% (alendronate) vs -0.52% (placebo); p=0.042
Trust score:4/5

tissue maturation

1 evidences

Randomized trial of sandwich bone augmentation with a collagen (bovine pericardium) barrier membrane showed preserved bone volume but delayed outer-layer maturation and less mineralization versus no membrane.

Trust comment: Randomized clinical trial but small sample and only a subset of biopsies were analyzable, limiting precision; directly evaluates a collagen membrane biomaterial.

Study Details

PMID:25220909
Participants:26
Impact:Delayed/slower maturation in collagen membrane group (outermost layer) compared with control
Trust score:3/5

mineralization/structure

1 evidences

Randomized trial of sandwich bone augmentation with a collagen (bovine pericardium) barrier membrane showed preserved bone volume but delayed outer-layer maturation and less mineralization versus no membrane.

Trust comment: Randomized clinical trial but small sample and only a subset of biopsies were analyzable, limiting precision; directly evaluates a collagen membrane biomaterial.

Study Details

PMID:25220909
Participants:26
Impact:Control specimens more structured and mineralized; collagen membrane group had less mineralization and more residual graft in loose matrix
Trust score:3/5

complete healing rate (12 weeks)

1 evidences

100 diabetic patients with chronic lower extremity ulcers were randomized to bioengineered skin substitute (BSS), dHACM, or standard wound care using collagen‑alginate dressings; dHACM produced the highest and fastest healing.

Trust comment: Prospective randomized multi-centre RCT with 100 analysed subjects; robust methodology though open‑label for treating clinicians.

Study Details

PMID:26695998
Participants:100
Impact:dHACM 97% vs BSS 73% vs SWC (collagen‑alginate) 51% (adjusted P=0.00019)
Trust score:4/5

mean time-to-heal

1 evidences

100 diabetic patients with chronic lower extremity ulcers were randomized to bioengineered skin substitute (BSS), dHACM, or standard wound care using collagen‑alginate dressings; dHACM produced the highest and fastest healing.

Trust comment: Prospective randomized multi-centre RCT with 100 analysed subjects; robust methodology though open‑label for treating clinicians.

Study Details

PMID:26695998
Participants:100
Impact:dHACM 23.6 days vs BSS 47.9 days vs SWC 57.4 days (adjusted P=3.2×10^-7)
Trust score:4/5

sinus lift extent (SL) at 6 months

1 evidences

30 patients underwent transcrestal sinus floor elevation randomized to DBBM or synthetic hydroxyapatite in a collagen matrix (S‑HA); both maintained lift, but S‑HA produced greater graft height and sinus lift at 6 months.

Trust comment: Randomized clinical trial but small (n=30); direct comparison includes a graft with a collagen matrix, results reported as significant but sample size limits generalizability.

Study Details

PMID:22092804
Participants:30
Impact:SL significantly greater with S‑HA (collagen matrix) compared with DBBM at 6 months
Trust score:3/5

apical graft height (aGH) at 6 months

1 evidences

30 patients underwent transcrestal sinus floor elevation randomized to DBBM or synthetic hydroxyapatite in a collagen matrix (S‑HA); both maintained lift, but S‑HA produced greater graft height and sinus lift at 6 months.

Trust comment: Randomized clinical trial but small (n=30); direct comparison includes a graft with a collagen matrix, results reported as significant but sample size limits generalizability.

Study Details

PMID:22092804
Participants:30
Impact:aGH significantly greater with S‑HA vs DBBM at 6 months
Trust score:3/5

post-operative morbidity

1 evidences

30 patients underwent transcrestal sinus floor elevation randomized to DBBM or synthetic hydroxyapatite in a collagen matrix (S‑HA); both maintained lift, but S‑HA produced greater graft height and sinus lift at 6 months.

Trust comment: Randomized clinical trial but small (n=30); direct comparison includes a graft with a collagen matrix, results reported as significant but sample size limits generalizability.

Study Details

PMID:22092804
Participants:30
Impact:limited complications and low post-op pain/discomfort in both groups
Trust score:3/5

lumbar spine bone loss

1 evidences

Randomized trial in premenopausal women receiving chemotherapy testing intermittent IV clodronate for prevention of rapid bone loss; biochemical bone turnover marker decreased during therapy but no clear prevention of bone loss.

Trust comment: Randomized allocation and relevant biochemical endpoints but small sample and limited clinical bone-sparing effect.

Study Details

PMID:15377842
Participants:45
Impact:at 6 months: -0.5% (clodronate) vs -1.4% (control); at 12 months: -3.9% vs -3.6%
Trust score:3/5

type I collagen metabolite (PINP)

1 evidences

Randomized trial in premenopausal women receiving chemotherapy testing intermittent IV clodronate for prevention of rapid bone loss; biochemical bone turnover marker decreased during therapy but no clear prevention of bone loss.

Trust comment: Randomized allocation and relevant biochemical endpoints but small sample and limited clinical bone-sparing effect.

Study Details

PMID:15377842
Participants:45
Impact:lower at 6 months: 22.6 µg/L (clodronate) vs 44.0 µg/L (control); p=0.0001
Trust score:3/5

VEGF (baseline high)

1 evidences

Large biomarker study in advanced HCC measuring multiple circulating proteins (including collagen IV) and tissue markers to assess prognosis and etiologic differences.

Trust comment: Large cohort biomarker analysis with standardized assays; observational associations are robust but not causal.

Study Details

PMID:27130844
Participants:503
Impact:above-median associated with significantly shorter overall survival
Trust score:4/5

sVEGFR1 (baseline high)

1 evidences

Large biomarker study in advanced HCC measuring multiple circulating proteins (including collagen IV) and tissue markers to assess prognosis and etiologic differences.

Trust comment: Large cohort biomarker analysis with standardized assays; observational associations are robust but not causal.

Study Details

PMID:27130844
Participants:503
Impact:above-median associated with significantly shorter overall survival
Trust score:4/5

collagen IV (plasma)

1 evidences

Large biomarker study in advanced HCC measuring multiple circulating proteins (including collagen IV) and tissue markers to assess prognosis and etiologic differences.

Trust comment: Large cohort biomarker analysis with standardized assays; observational associations are robust but not causal.

Study Details

PMID:27130844
Participants:503
Impact:measured by ELISA; no specific prognostic association reported in the presented summary
Trust score:4/5

TRAP-induced platelet aggregation (LTA)

1 evidences

Pharmacodynamic substudy of vorapaxar versus placebo showing potent inhibition of PAR-1–mediated platelet aggregation in ACS patients.

Trust comment: Well-characterized randomized substudy with objective platelet function assays; strong pharmacodynamic signal.

Study Details

PMID:24402559
Participants:249
Impact:maximal response at 2 h: placebo 68% vs vorapaxar 3% (marked inhibition)
Trust score:4/5

ADP-induced inhibition

1 evidences

Pharmacodynamic substudy of vorapaxar versus placebo showing potent inhibition of PAR-1–mediated platelet aggregation in ACS patients.

Trust comment: Well-characterized randomized substudy with objective platelet function assays; strong pharmacodynamic signal.

Study Details

PMID:24402559
Participants:249
Impact:greater inhibition in vorapaxar group at 4 hours and 1 month (p<0.01)
Trust score:4/5

PAR-1 receptor number

1 evidences

Pharmacodynamic substudy of vorapaxar versus placebo showing potent inhibition of PAR-1–mediated platelet aggregation in ACS patients.

Trust comment: Well-characterized randomized substudy with objective platelet function assays; strong pharmacodynamic signal.

Study Details

PMID:24402559
Participants:249
Impact:decreased from 225 to 179 at 1 month in vorapaxar group (p=0.004)
Trust score:4/5

serum C-terminal telopeptide of type-1 collagen (bone resorption marker)

1 evidences

Randomized placebo-controlled trial of 50 mg DHEA daily for 1 year showing hormonal changes and modest bone benefits in women but not men.

Trust comment: Large randomized placebo-controlled trial with sex-specific biochemical and BMD endpoints; well conducted.

Study Details

PMID:18084691
Participants:225
Impact:decreased in women (p=0.03)
Trust score:4/5

visual analogue scale (patient assessment)

1 evidences

Polylactic acid injections improved facial appearance, patient self-perception, and anxiety/depression scores in HIV-associated facial lipoatrophy.

Trust comment: Randomized open-label trial (n=30) showing patient-reported and photographic improvements; small sample and open-label design lower certainty.

Study Details

PMID:15012646
Participants:30
Impact:immediate-treatment median score 7 vs delayed 1 at week 12 (improved)
Trust score:3/5

HADS anxiety score

1 evidences

Polylactic acid injections improved facial appearance, patient self-perception, and anxiety/depression scores in HIV-associated facial lipoatrophy.

Trust comment: Randomized open-label trial (n=30) showing patient-reported and photographic improvements; small sample and open-label design lower certainty.

Study Details

PMID:15012646
Participants:30
Impact:lower in immediate group (6 vs 9 at week 12; trend p=0.056)
Trust score:3/5

duration of benefit

1 evidences

Polylactic acid injections improved facial appearance, patient self-perception, and anxiety/depression scores in HIV-associated facial lipoatrophy.

Trust comment: Randomized open-label trial (n=30) showing patient-reported and photographic improvements; small sample and open-label design lower certainty.

Study Details

PMID:15012646
Participants:30
Impact:improvements persisted through week 24 (≈18 weeks beyond last injection)
Trust score:3/5

peri-implant marginal bone level change (1 year)

1 evidences

Randomized multicenter trial comparing immediate post-extractive implants vs delayed implants (delayed group received socket preservation with bovine bone and a resorbable collagen barrier); aesthetics similar, more complications with immediate implants.

Trust comment: Multicenter randomized trial with blinded assessors and 1-year follow-up; collagen membrane was used in the delayed (socket preservation) arm but not isolated as a single factor.

Study Details

PMID:26669545
Participants:106
Impact:Immediate mean loss 0.23 mm vs Delayed 0.29 mm (difference −0.06 mm; P=0.036)
Trust score:4/5

complete wound healing at 12 weeks

1 evidences

Randomized multicenter trial (100 subjects) comparing bioactive split‑thickness skin allograft (contains native collagen and living cells) plus SOC versus SOC alone for diabetic foot ulcers: allograft markedly increased 12‑week healing rates and accelerated healing.

Trust comment: Large randomized multicentre trial with ITT analysis and blinded adjudication showing robust benefits; limitation: lack of investigator blinding and sponsor involvement declared.

Study Details

PMID:35080127
Participants:100
Impact:+40 percentage points (76% vs 36%; P=0.00056) — higher closure with bioactive allograft
Trust score:4/5

percentage area reduction (PAR) at 12 weeks

1 evidences

Randomized multicenter trial (100 subjects) comparing bioactive split‑thickness skin allograft (contains native collagen and living cells) plus SOC versus SOC alone for diabetic foot ulcers: allograft markedly increased 12‑week healing rates and accelerated healing.

Trust comment: Large randomized multicentre trial with ITT analysis and blinded adjudication showing robust benefits; limitation: lack of investigator blinding and sponsor involvement declared.

Study Details

PMID:35080127
Participants:100
Impact:+28.2 percentage points (77.8% vs 49.6%; P=0.0019) — greater area reduction with allograft
Trust score:4/5

time to heal (mean)

1 evidences

Randomized multicenter trial (100 subjects) comparing bioactive split‑thickness skin allograft (contains native collagen and living cells) plus SOC versus SOC alone for diabetic foot ulcers: allograft markedly increased 12‑week healing rates and accelerated healing.

Trust comment: Large randomized multicentre trial with ITT analysis and blinded adjudication showing robust benefits; limitation: lack of investigator blinding and sponsor involvement declared.

Study Details

PMID:35080127
Participants:100
Impact:−18.4 days faster (46.9 days vs 65.3 days; P=0.0019) — shorter time to closure with allograft
Trust score:4/5

quadriceps cross-sectional area (qCSA)

1 evidences

1-year randomized trial in healthy adults >65 testing twice-daily protein supplements (including a collagen protein arm); collagen supplementation alone did not improve muscle size, strength, function, or body composition versus carbohydrate control.

Trust comment: Large, 1-year randomized controlled trial with robust completion (184), so findings on oral collagen supplementation are credible.

Study Details

PMID:33564844
Participants:184
Impact:no change vs carbohydrate (no significant difference)
Trust score:4/5

knee extensor strength (dynamic and isometric)

1 evidences

1-year randomized trial in healthy adults >65 testing twice-daily protein supplements (including a collagen protein arm); collagen supplementation alone did not improve muscle size, strength, function, or body composition versus carbohydrate control.

Trust comment: Large, 1-year randomized controlled trial with robust completion (184), so findings on oral collagen supplementation are credible.

Study Details

PMID:33564844
Participants:184
Impact:no change vs carbohydrate (no significant difference)
Trust score:4/5

functional capabilities / body composition

1 evidences

1-year randomized trial in healthy adults >65 testing twice-daily protein supplements (including a collagen protein arm); collagen supplementation alone did not improve muscle size, strength, function, or body composition versus carbohydrate control.

Trust comment: Large, 1-year randomized controlled trial with robust completion (184), so findings on oral collagen supplementation are credible.

Study Details

PMID:33564844
Participants:184
Impact:no change vs carbohydrate (no significant difference)
Trust score:4/5

clinically relevant postoperative pancreatic fistula (POPF) rate

1 evidences

Large multicenter randomized trial testing a fibrin–collagen sealant sponge (TachoSil) on pancreatic remnant closure; TachoSil did not reduce rate or severity of postoperative pancreatic fistula.

Trust comment: Large multicenter randomized controlled trial directly testing a collagen-containing surgical product; robust design and sample size support reliability despite negative result.

Study Details

PMID:26160763
Participants:270
Impact:30.6% with TachoSil vs 24.3% without (P=0.276) — no significant reduction
Trust score:4/5

overall POPF rate

1 evidences

Large multicenter randomized trial testing a fibrin–collagen sealant sponge (TachoSil) on pancreatic remnant closure; TachoSil did not reduce rate or severity of postoperative pancreatic fistula.

Trust comment: Large multicenter randomized controlled trial directly testing a collagen-containing surgical product; robust design and sample size support reliability despite negative result.

Study Details

PMID:26160763
Participants:270
Impact:54.5% with TachoSil vs 56.6% without (P=0.807) — no significant difference
Trust score:4/5

CTX-1 (C-terminal telopeptide of collagen I) association with global cognition decline

1 evidences

Observational cohort relating baseline bone-derived biomarkers (including CTX-1, a collagen type I turnover marker) to subsequent cognitive decline; higher CTX-1 associated with greater cognitive decline over 18 months.

Trust comment: Well-characterized community cohort with repeated cognitive testing; observational design limits causal inference but biomarker associations are statistically supported.

Study Details

PMID:29432613
Participants:103
Impact:Baseline CTX-1 related to annual rate of change in global cognition (p=0.046) — higher CTX-1 associated with faster decline
Trust score:3/5

TRAIL association with cognition

1 evidences

Observational cohort relating baseline bone-derived biomarkers (including CTX-1, a collagen type I turnover marker) to subsequent cognitive decline; higher CTX-1 associated with greater cognitive decline over 18 months.

Trust comment: Well-characterized community cohort with repeated cognitive testing; observational design limits causal inference but biomarker associations are statistically supported.

Study Details

PMID:29432613
Participants:103
Impact:Baseline TRAIL strongly related to annual change in global cognition (p<0.001)
Trust score:3/5

Dkk1 association with cognition

1 evidences

Observational cohort relating baseline bone-derived biomarkers (including CTX-1, a collagen type I turnover marker) to subsequent cognitive decline; higher CTX-1 associated with greater cognitive decline over 18 months.

Trust comment: Well-characterized community cohort with repeated cognitive testing; observational design limits causal inference but biomarker associations are statistically supported.

Study Details

PMID:29432613
Participants:103
Impact:Baseline Dkk1 related to annual rate of change in global cognition (p=0.014)
Trust score:3/5

sLOXL2 association with IPF progression (ARTEMIS-IPF)

1 evidences

Higher serum LOXL2 levels (an enzyme promoting collagen cross-linking) were associated with increased risk of IPF progression and higher mortality in two cohorts.

Trust comment: Observational analysis of two cohorts with moderate sample sizes showing association of a collagen cross-linking enzyme with IPF progression; findings require external validation.

Study Details

PMID:24177001
Participants:173
Impact:HR 5.41 for progression when sLOXL2 >800 pg/mL (95% CI 1.65–17.73)
Trust score:3/5

sLOXL2 association with IPF progression (GAP subset)

1 evidences

Higher serum LOXL2 levels (an enzyme promoting collagen cross-linking) were associated with increased risk of IPF progression and higher mortality in two cohorts.

Trust comment: Observational analysis of two cohorts with moderate sample sizes showing association of a collagen cross-linking enzyme with IPF progression; findings require external validation.

Study Details

PMID:24177001
Participants:173
Impact:HR 1.78 for progression when sLOXL2 >700 pg/mL (95% CI 1.01–3.11)
Trust score:3/5

sLOXL2 association with mortality (GAP overall)

1 evidences

Higher serum LOXL2 levels (an enzyme promoting collagen cross-linking) were associated with increased risk of IPF progression and higher mortality in two cohorts.

Trust comment: Observational analysis of two cohorts with moderate sample sizes showing association of a collagen cross-linking enzyme with IPF progression; findings require external validation.

Study Details

PMID:24177001
Participants:173
Impact:HR 2.28 for mortality (95% CI 1.18–4.38)
Trust score:3/5

Neck Disability Index (NDI) improvement

1 evidences

A randomized multicenter FDA IDE trial found the i-Factor bone graft (contains a synthetic collagen fragment P-15) noninferior to autograft for single-level ACDF with high fusion rates and similar safety; overall composite success was higher with i-Factor.

Trust comment: Large randomized, multicenter FDA pivotal trial showing noninferiority and higher overall success for a device that includes a synthetic collagen fragment (P-15); well-conducted with robust endpoints.

Study Details

PMID:26825787
Participants:319
Impact:Mean improvement ~28.75 (i-Factor) vs 27.40 (autograft) at 12 months
Trust score:4/5

Overall success rate (fusion+NDI+neurological+safety)

1 evidences

A randomized multicenter FDA IDE trial found the i-Factor bone graft (contains a synthetic collagen fragment P-15) noninferior to autograft for single-level ACDF with high fusion rates and similar safety; overall composite success was higher with i-Factor.

Trust comment: Large randomized, multicenter FDA pivotal trial showing noninferiority and higher overall success for a device that includes a synthetic collagen fragment (P-15); well-conducted with robust endpoints.

Study Details

PMID:26825787
Participants:319
Impact:i-Factor 68.75% vs autograft 56.94% (P=0.0382)
Trust score:4/5

urinary COL6A1 (collagen α-1(VI) chain)

1 evidences

Proteomic analysis of urine from TOPCAT participants identified multiple urinary proteins (including collagen-derived peptides) associated with lower or higher risk of death or HF admission.

Trust comment: Well-powered, adjusted proteomic analysis in a nested cohort (n=426) identifying associations of collagen-derived urinary peptides with outcomes; observational design and lack of external validation limit causal inference.

Study Details

PMID:38639358
Participants:426
Impact:Inversely associated with death or HF admission (DHFA): nonadjusted HR 0.64; adjusted HR 0.65 (95% CI ~0.52–0.81); P≈0.0486
Trust score:4/5

urinary COL15A1 (collagen α-1(XV) chain)

1 evidences

Proteomic analysis of urine from TOPCAT participants identified multiple urinary proteins (including collagen-derived peptides) associated with lower or higher risk of death or HF admission.

Trust comment: Well-powered, adjusted proteomic analysis in a nested cohort (n=426) identifying associations of collagen-derived urinary peptides with outcomes; observational design and lack of external validation limit causal inference.

Study Details

PMID:38639358
Participants:426
Impact:Inversely associated with DHFA in unadjusted analysis (HR ~0.64); association attenuated after adjustment (adjusted HR ~0.67, P≈0.068)
Trust score:4/5

composite outcome (DHFA) event count

1 evidences

Proteomic analysis of urine from TOPCAT participants identified multiple urinary proteins (including collagen-derived peptides) associated with lower or higher risk of death or HF admission.

Trust comment: Well-powered, adjusted proteomic analysis in a nested cohort (n=426) identifying associations of collagen-derived urinary peptides with outcomes; observational design and lack of external validation limit causal inference.

Study Details

PMID:38639358
Participants:426
Impact:100 composite events observed in n=426 (64 deaths + 54 HF admissions) used for association analyses
Trust score:4/5

mineralized tissue formation

1 evidences

In patients undergoing tooth extraction and socket grafting, a PLGA‑coated β‑tricalcium phosphate graft produced less new mineralized tissue at 20 weeks than freeze‑dried bone allograft, though implant placement and short‑term implant outcomes were comparable.

Trust comment: Randomized multicenter trial with objective radiographic and histomorphometric endpoints but modest sample size and attrition (43 treated, 32 completed).

Study Details

PMID:32996128
Participants:32
Impact:+11.2 percentage points (38.2% vs 27.0%; P < 0.05) higher with FDBA + RACD versus PLGA-β-TCP
Trust score:4/5

alveolar bone dimensions (horizontal width / midbuccal-midlingual height / ridge volume)

1 evidences

In patients undergoing tooth extraction and socket grafting, a PLGA‑coated β‑tricalcium phosphate graft produced less new mineralized tissue at 20 weeks than freeze‑dried bone allograft, though implant placement and short‑term implant outcomes were comparable.

Trust comment: Randomized multicenter trial with objective radiographic and histomorphometric endpoints but modest sample size and attrition (43 treated, 32 completed).

Study Details

PMID:32996128
Participants:32
Impact:no significant difference between groups
Trust score:4/5

implant survival / peri-implant bone level

1 evidences

In patients undergoing tooth extraction and socket grafting, a PLGA‑coated β‑tricalcium phosphate graft produced less new mineralized tissue at 20 weeks than freeze‑dried bone allograft, though implant placement and short‑term implant outcomes were comparable.

Trust comment: Randomized multicenter trial with objective radiographic and histomorphometric endpoints but modest sample size and attrition (43 treated, 32 completed).

Study Details

PMID:32996128
Participants:32
Impact:no implant failures; marginal bone level change negligible
Trust score:4/5

IL-1beta (GCF)

1 evidences

Higher GCF inflammation and collagen-breakdown biomarkers predicted later periodontal attachment and bone loss; subantimicrobial-dose doxycycline modified risk.

Trust comment: Double-masked, placebo-controlled randomized trial with clear biomarker and clinical outcome measures in humans.

Study Details

PMID:20151804
Participants:128
Impact:Increase in year 1 associated with OR=1.67 for subsequent attachment loss (P=0.01)
Trust score:4/5

MMP-8 (GCF)

1 evidences

Higher GCF inflammation and collagen-breakdown biomarkers predicted later periodontal attachment and bone loss; subantimicrobial-dose doxycycline modified risk.

Trust comment: Double-masked, placebo-controlled randomized trial with clear biomarker and clinical outcome measures in humans.

Study Details

PMID:20151804
Participants:128
Impact:Increase in year 1 associated with OR=1.50 for subsequent attachment loss (P=0.02)
Trust score:4/5

ICTP (type I collagen telopeptide, GCF)

1 evidences

Higher GCF inflammation and collagen-breakdown biomarkers predicted later periodontal attachment and bone loss; subantimicrobial-dose doxycycline modified risk.

Trust comment: Double-masked, placebo-controlled randomized trial with clear biomarker and clinical outcome measures in humans.

Study Details

PMID:20151804
Participants:128
Impact:Elevated baseline ICTP associated with OR=1.98 for alveolar bone density loss (P=0.0001) in placebo group
Trust score:4/5

biochemical leakage / POPF

1 evidences

Application of a fibrinogen/thrombin-coated collagen patch did not significantly reduce clinically relevant pancreatic fistulas or hospital stay.

Trust comment: Randomized clinical trial directly tested a collagen patch but was single-center and may be underpowered for some outcomes.

Study Details

PMID:31502003
Participants:124
Impact:Intervention 25.8% vs control 37.1% (difference -11.3 percentage points; not statistically significant)
Trust score:3/5

clinically relevant POPF

1 evidences

Application of a fibrinogen/thrombin-coated collagen patch did not significantly reduce clinically relevant pancreatic fistulas or hospital stay.

Trust comment: Randomized clinical trial directly tested a collagen patch but was single-center and may be underpowered for some outcomes.

Study Details

PMID:31502003
Participants:124
Impact:Intervention 6.5% vs control 6.5% (no difference)
Trust score:3/5

absolute liver fat content

1 evidences

Aldafermin reduced liver fat and lowered a type III collagen biomarker, with trends toward fibrosis improvement.

Trust comment: Well-conducted double-blind phase 2 RCT with histologic endpoints but small sample size limits precision.

Study Details

PMID:32781086
Participants:78
Impact:Aldafermin -7.7% vs placebo -2.7% (difference -5.0%, P=0.002)
Trust score:4/5

Pro-C3 (type III collagen neoepitope)

1 evidences

Aldafermin reduced liver fat and lowered a type III collagen biomarker, with trends toward fibrosis improvement.

Trust comment: Well-conducted double-blind phase 2 RCT with histologic endpoints but small sample size limits precision.

Study Details

PMID:32781086
Participants:78
Impact:Significant decrease with aldafermin versus placebo (exact magnitude not reported)
Trust score:4/5

fibrosis improvement (≥1 stage)

1 evidences

Aldafermin reduced liver fat and lowered a type III collagen biomarker, with trends toward fibrosis improvement.

Trust comment: Well-conducted double-blind phase 2 RCT with histologic endpoints but small sample size limits precision.

Study Details

PMID:32781086
Participants:78
Impact:38% with aldafermin vs 18% with placebo (P=0.10; trend not statistically significant)
Trust score:4/5

medial femoral bone area progression

1 evidences

MIV-711 did not improve pain but significantly reduced bone area progression, reduced cartilage thinning, and lowered collagen biomarker levels.

Trust comment: Randomized phase 2a trial with imaging and biomarker endpoints; moderate sample size but relatively short duration.

Study Details

PMID:31887743
Participants:244
Impact:Significantly reduced with MIV-711 (P=0.002 for 100 mg; P=0.004 for 200 mg)
Trust score:4/5

collagen C-telopeptide biomarkers (type I and II)

1 evidences

MIV-711 did not improve pain but significantly reduced bone area progression, reduced cartilage thinning, and lowered collagen biomarker levels.

Trust comment: Randomized phase 2a trial with imaging and biomarker endpoints; moderate sample size but relatively short duration.

Study Details

PMID:31887743
Participants:244
Impact:Substantial reductions reported (exact values not provided)
Trust score:4/5

GP IIb/IIIa activity

1 evidences

Patterns of platelet inhibition differed by treatment; ER-DP+ASA caused later reductions in multiple platelet activation markers, while clopidogrel (with ASA) inhibited collagen-induced aggregation earlier.

Trust comment: Small, single-blind randomized trial using surrogate platelet biomarkers over 30 days; limited size and short duration.

Study Details

PMID:18343263
Participants:60
Impact:ER-DP+ASA: delayed reduction at day 30 (P=0.02); clopidogrel: reduction seen by day 15 (P=0.01)
Trust score:3/5

PECAM-1 expression

1 evidences

Patterns of platelet inhibition differed by treatment; ER-DP+ASA caused later reductions in multiple platelet activation markers, while clopidogrel (with ASA) inhibited collagen-induced aggregation earlier.

Trust comment: Small, single-blind randomized trial using surrogate platelet biomarkers over 30 days; limited size and short duration.

Study Details

PMID:18343263
Participants:60
Impact:ER-DP+ASA: reduction at day 30 (P=0.03); clopidogrel: reduction at day 15 (P=0.03)
Trust score:3/5

collagen metabolism biomarkers (e.g., COL1A1, MMP-2)

1 evidences

Spironolactone reduced multiple plasma biomarkers including those of collagen metabolism, suggesting antifibrotic effects.

Trust comment: Large randomized trial with extensive proteomic profiling; biomarker changes are biologically plausible though clinical effect inference is indirect.

Study Details

PMID:33549556
Participants:527
Impact:Decreased levels reported (exact magnitudes not provided)
Trust score:4/5

brain natriuretic peptide (BNP)

1 evidences

Spironolactone reduced multiple plasma biomarkers including those of collagen metabolism, suggesting antifibrotic effects.

Trust comment: Large randomized trial with extensive proteomic profiling; biomarker changes are biologically plausible though clinical effect inference is indirect.

Study Details

PMID:33549556
Participants:527
Impact:Reduced (exact magnitude not provided)
Trust score:4/5

inflammation/thrombosis biomarkers (e.g., IL17A, VEGF)

1 evidences

Spironolactone reduced multiple plasma biomarkers including those of collagen metabolism, suggesting antifibrotic effects.

Trust comment: Large randomized trial with extensive proteomic profiling; biomarker changes are biologically plausible though clinical effect inference is indirect.

Study Details

PMID:33549556
Participants:527
Impact:Reduced (exact magnitudes not provided)
Trust score:4/5

blood loss during hemostasis

1 evidences

A collagen-derived hemostatic gel (Floseal) produced faster hemostasis, less blood loss, and quicker return to diet than cautery in children having adenoidectomy.

Trust comment: Randomized controlled trial (n=70) showing consistent objective benefits for a collagen-derived product; nonblinded but multicenter and outcomes are objective.

Study Details

PMID:15523433
Participants:70
Impact:-26.9 mL (2.5 vs 29.4 mL; Floseal vs cautery, P < 0.001)
Trust score:4/5

time to return to regular diet

1 evidences

A collagen-derived hemostatic gel (Floseal) produced faster hemostasis, less blood loss, and quicker return to diet than cautery in children having adenoidectomy.

Trust comment: Randomized controlled trial (n=70) showing consistent objective benefits for a collagen-derived product; nonblinded but multicenter and outcomes are objective.

Study Details

PMID:15523433
Participants:70
Impact:-1.4 days (2.7 vs 4.1 days; Floseal vs cautery, P < 0.001)
Trust score:4/5

cosmetic VAS score

1 evidences

Absorbable plain gut (collagen-derived) sutures produced similar or slightly better long-term cosmetic outcomes than nylon sutures in children.

Trust comment: Randomized clinical trial in children comparing a collagen-derived suture to nylon with objective and blinded long-term assessment, though some loss to follow-up.

Study Details

PMID:15231459
Participants:63
Impact:+13 points (79 vs 66 average VAS at 4 months; plain gut vs nylon)
Trust score:4/5

infection (cases)

1 evidences

Absorbable plain gut (collagen-derived) sutures produced similar or slightly better long-term cosmetic outcomes than nylon sutures in children.

Trust comment: Randomized clinical trial in children comparing a collagen-derived suture to nylon with objective and blinded long-term assessment, though some loss to follow-up.

Study Details

PMID:15231459
Participants:63
Impact:0 vs 2 cases (plain gut vs nylon, p = 0.3)
Trust score:4/5

serum CTx (acute)

1 evidences

3-month randomized placebo-controlled trial in postmenopausal women: oral salmon calcitonin reduced bone resorption markers markedly acutely and modestly at 3 months; all participants received calcium plus 400 IU vitamin D daily but vitamin D effect was not evaluated.

Trust comment: Large randomized, double-blind, placebo-controlled dose-ranging trial with objective biomarker endpoints and good reproducibility.

Study Details

PMID:15312255
Participants:277
Impact:-60.8% to -81.8% (dose-dependent nadirs 2–3 h after first dose)
Trust score:4/5

pre-dose serum CTx (month 3, 1.0 mg dose)

1 evidences

3-month randomized placebo-controlled trial in postmenopausal women: oral salmon calcitonin reduced bone resorption markers markedly acutely and modestly at 3 months; all participants received calcium plus 400 IU vitamin D daily but vitamin D effect was not evaluated.

Trust comment: Large randomized, double-blind, placebo-controlled dose-ranging trial with objective biomarker endpoints and good reproducibility.

Study Details

PMID:15312255
Participants:277
Impact:-18.9% (placebo-corrected, P < 0.05)
Trust score:4/5

urinary CTx (month 3, 1.0 mg dose)

1 evidences

3-month randomized placebo-controlled trial in postmenopausal women: oral salmon calcitonin reduced bone resorption markers markedly acutely and modestly at 3 months; all participants received calcium plus 400 IU vitamin D daily but vitamin D effect was not evaluated.

Trust comment: Large randomized, double-blind, placebo-controlled dose-ranging trial with objective biomarker endpoints and good reproducibility.

Study Details

PMID:15312255
Participants:277
Impact:-20.5% (placebo-corrected, P < 0.05)
Trust score:4/5

joint space width (JSW)

1 evidences

Higher plasma LBP and sTLR4 were associated with worse knee OA progression and increased urinary collagen-breakdown marker over 16–18 months.

Trust comment: Large (n=431) human cohort from a clinical trial with multivariable adjustment; observational biomarker associations rather than a collagen intervention.

Study Details

PMID:30144513
Participants:431
Impact:-0.07 to -0.1 mm change in JSW per SD higher LBP (parameter estimates)
Trust score:4/5

urinary C-telopeptide of type II collagen (uCTX-II)

1 evidences

Higher plasma LBP and sTLR4 were associated with worse knee OA progression and increased urinary collagen-breakdown marker over 16–18 months.

Trust comment: Large (n=431) human cohort from a clinical trial with multivariable adjustment; observational biomarker associations rather than a collagen intervention.

Study Details

PMID:30144513
Participants:431
Impact:+0.0017 to +0.0020 change in uCTX-II per SD higher sTLR4 (parameter estimates)
Trust score:4/5

type 1 collagen cross-linked C-telopeptide (CTx)

1 evidences

ART initiation increased bone turnover markers; 25(OH)D levels decreased modestly over time in both arms but this was an observational measurement, not a vitamin D intervention.

Trust comment: Large, double-blind, randomized phase III trial (n=833) with appropriate analyses and prespecified biomarker assessments.

Study Details

PMID:26355674
Participants:833
Impact:Greater percent increase from baseline in EFV/FTC/TDF vs DTG+ABC/3TC at weeks 48, 96, 144 (P<0.001 at 48/96; P=0.002 at 144)
Trust score:5/5

bone formation markers (osteocalcin, BSAP, P1NP)

1 evidences

ART initiation increased bone turnover markers; 25(OH)D levels decreased modestly over time in both arms but this was an observational measurement, not a vitamin D intervention.

Trust comment: Large, double-blind, randomized phase III trial (n=833) with appropriate analyses and prespecified biomarker assessments.

Study Details

PMID:26355674
Participants:833
Impact:Larger increases in EFV/FTC/TDF arm versus DTG+ABC/3TC at all time points (significant differences)
Trust score:5/5

vitamin D

1 evidences

ART initiation increased bone turnover markers; 25(OH)D levels decreased modestly over time in both arms but this was an observational measurement, not a vitamin D intervention.

Trust comment: Large, double-blind, randomized phase III trial (n=833) with appropriate analyses and prespecified biomarker assessments.

Study Details

PMID:26355674
Participants:833
Impact:Decreased in both arms; DTG+ABC/3TC: −7%, −5%, −2% at weeks 48/96/144; EFV/FTC/TDF: −10%, −10%, −4% at 48/96/144
Trust score:5/5

KOOS pain and symptom scores

1 evidences

Phase-II randomized trial where a type-I collagen scaffold (NeoCart) seeded with autologous chondrocytes improved several knee outcomes vs microfracture over two years.

Trust comment: Randomized phase-II trial directly using a collagen scaffold (clinical relevance to collagen); small sample (n=30) limits generalizability but randomized design supports moderate trust.

Study Details

PMID:22637204
Participants:30
Impact:Greater improvement with NeoCart vs microfracture (p<0.05 at multiple timepoints)
Trust score:3/5

IKDC and KOOS sports / QOL

1 evidences

Phase-II randomized trial where a type-I collagen scaffold (NeoCart) seeded with autologous chondrocytes improved several knee outcomes vs microfracture over two years.

Trust comment: Randomized phase-II trial directly using a collagen scaffold (clinical relevance to collagen); small sample (n=30) limits generalizability but randomized design supports moderate trust.

Study Details

PMID:22637204
Participants:30
Impact:Greater improvement with NeoCart at 12 and 24 months (p<0.05)
Trust score:3/5

therapeutic responder rate

1 evidences

Phase-II randomized trial where a type-I collagen scaffold (NeoCart) seeded with autologous chondrocytes improved several knee outcomes vs microfracture over two years.

Trust comment: Randomized phase-II trial directly using a collagen scaffold (clinical relevance to collagen); small sample (n=30) limits generalizability but randomized design supports moderate trust.

Study Details

PMID:22637204
Participants:30
Impact:NeoCart responders: 43% vs 25% at 6 months; 76% vs 22% at 12 months; sustained at 24 months
Trust score:3/5

graft take (5–7 days)

1 evidences

A porcine collagen-elastin dermal substitute plus STSG slowed early graft take and epithelialization versus STSG alone but showed improved scar elasticity at 12 months.

Trust comment: Phase I/II intrapatient randomized trial with objective measures and long-term follow-up but modest sample size and early wound-healing delays.

Study Details

PMID:37729164
Participants:24
Impact:-15 percentage points (80% vs 95%; p=0.003)
Trust score:3/5

scar elasticity (Cutometer Uf and Ue at 12 months)

1 evidences

A porcine collagen-elastin dermal substitute plus STSG slowed early graft take and epithelialization versus STSG alone but showed improved scar elasticity at 12 months.

Trust comment: Phase I/II intrapatient randomized trial with objective measures and long-term follow-up but modest sample size and early wound-healing delays.

Study Details

PMID:37729164
Participants:24
Impact:improved (Uf 0.69 vs 0.59, p=0.034; Ue 0.66 vs 0.54, p=0.036)
Trust score:3/5

early wound healing (EHI)

1 evidences

Minimally invasive periodontal surgery produced clinical attachment gains at 1 year; adding deproteinized bovine bone mineral plus a collagen membrane did not improve 1-year outcomes versus surgery alone.

Trust comment: Randomized trial directly tested a collagen-containing membrane as a regenerative material; small sample size limits certainty but design is appropriate.

Study Details

PMID:34414521
Participants:31
Impact:better at 1 week in MISTms-alone vs combined (fewer early healing issues)
Trust score:3/5

buccal-side horizontal bone gain (2 mm below implant abutment)

1 evidences

Two types of absorbable collagen membranes (porcine SIS and bovine pericardium) produced similar buccal horizontal bone gain and similar wound healing after single-tooth GBR in diabetic patients at 6 months.

Trust comment: Small randomized prospective study (n=48) directly comparing two collagen membrane products with objective imaging and wound-healing outcomes; limited sample size.

Study Details

PMID:39848799
Participants:48
Impact:no significant difference (PSIS median 69.1 mm vs BPT 71.4 mm; P = 0.805)
Trust score:3/5

wound healing score (1 and 4 weeks)

1 evidences

Two types of absorbable collagen membranes (porcine SIS and bovine pericardium) produced similar buccal horizontal bone gain and similar wound healing after single-tooth GBR in diabetic patients at 6 months.

Trust comment: Small randomized prospective study (n=48) directly comparing two collagen membrane products with objective imaging and wound-healing outcomes; limited sample size.

Study Details

PMID:39848799
Participants:48
Impact:no significant difference at 1 week (P = 0.627) or 4 weeks (P = 0.539)
Trust score:3/5