Key papers ✓ 6~ 2? 1

• ✓ Positive human RCTInt J Cosmet Sci · 2005

  Topical palmitoyl pentapeptide provides improvement in photoaged human facial skin.

  Humans93 peopleRandomizedPlacebo-controlledDouble-blind12 weeks

  Double-blind, placebo-controlled, split-face, left-right randomized study

  93 women aged 35-55 in a 12-week double-blind split-face RCT: moisturizer with 3 ppm pal-KTTKS significantly reduced wrinkles/fine lines vs the same moisturizer without it, by image analysis and expert grading; well tolerated.

  Key resultSignificant improvement vs placebo control for reduction in wrinkles/fine lines (3 ppm pal-KTTKS)

  Study details

  Studied

  Caucasian women aged 35-55 with photoaged facial skin

  Compared with

  Same moisturizer without pal-KTTKS

  Main outcome

  Wrinkles and fine lines by image analysis and expert grading

  Sample

  93 Caucasian women aged 35-55

  Authors' conclusion

  Pal-KTTKS was well tolerated and gave significant wrinkle and fine-line improvement versus the control moisturizer by technical and expert grading and self-assessment.

  Limitations

  Abstract gives no effect sizes or p-values; product-sponsored design not described.

  DOI 10.1111/j.1467-2494.2005.00261.xPubMed 18492182
• ? Inconclusive human RCTJ Clin Aesthet Dermatol · 2023

  Double-blind, Randomized Trial on the Effectiveness of Acetylhexapeptide-3 Cream and Palmitoyl Pentapeptide-4 Cream for Crow's Feet.

  Humans21 peopleRandomizedPlacebo-controlledDouble-blind8 weeks

  Double-blind randomized trial: acetylhexapeptide-3 cream, palmitoyl pentapeptide-4 cream or placebo, twice daily

  21 Indonesian women, 8 weeks, three arms (acetyl hexapeptide-3, palmitoyl pentapeptide-4, placebo cream) for crow's feet: palmitoyl pentapeptide-4 appeared to give the best results, but the authors describe it as an initial study needing larger samples.

  Study details

  Studied

  Indonesian women aged 26 to 55 with crow's feet

  Compared with

  Placebo cream and acetylhexapeptide-3 cream

  Main outcome

  Skin hydration, barrier, elasticity, photographs and Crow's Feet Grading Scale

  Sample

  21 Indonesian women across three groups

  Authors' conclusion

  Palmitoyl pentapeptide-4 appeared to show better results than acetylhexapeptide-3 and placebo; the authors call it an initial study needing more samples and longer duration.

  Limitations

  Very small sample (21 across three arms), short duration, no numerical results in the abstract.

  PubMed 36909866Free full text
• ✓ Positive in vitroMol Pharm · 2013

  Collagen stimulating effect of peptide amphiphile C16-KTTKS on human fibroblasts.

  Cells / lab

  In vitro study of peptide amphiphile C16-KTTKS solutions and self-assembly

  C16-KTTKS stimulated collagen production by human dermal and corneal fibroblasts in a concentration-dependent manner close to its self-assembly concentration.

  Study details

  Studied

  Human dermal and corneal fibroblasts

  Main outcome

  Collagen production

  Authors' conclusion

  C16-KTTKS stimulated collagen production in a concentration-dependent manner close to its critical aggregation concentration, suggesting self-assembly and collagen stimulation are inter-related.

  Limitations

  In vitro only.

  DOI 10.1021/mp300549dPubMed 23320752
• ✓ Positive in vitroJ Pept Sci · 2026

  Nanostructure and Collagen-Stimulating Activity of Cationic Pentapeptide Lipopeptides.

  Cells / lab

  In vitro study of self-assembly, cytocompatibility and collagen production of C16-KTTKS and C16-RTTRS

  C16-KTTKS (Matrixyl) stimulated collagen production in human dermal fibroblasts at low concentration (0.0062 wt%) and was cytocompatible at sufficiently low concentrations.

  Study details

  Studied

  Human dermal fibroblasts (HDFa)

  Compared with

  C16-RTTRS variant; TFA vs acetate salt forms

  Main outcome

  Cell viability and collagen production

  Authors' conclusion

  Both lipopeptides were cytocompatible at sufficiently low concentration and stimulated collagen production in HDFa at 0.0062 wt%; counterion had no significant effect.

  Limitations

  In vitro only.

  DOI 10.1002/psc.70111PubMed 42317129Free full text
  SCHEME 1 FIGURE 7
• ✓ Positive animalACS Omega · 2022

  Matrixyl Patch vs Matrixyl Cream: A Comparative In Vivo Investigation of Matrixyl (MTI) Effect on Wound Healing.

  Animalssize not reportedRandomizedSham/vehicle control21 days

  Randomized in vivo wound-healing study comparing Matrixyl patches (0.1 and 1 mg), Matrixyl cream, vehicle controls and Comfeel

  In an animal wound model, Matrixyl patches or cream improved wound healing by 63.5-81.8% vs sham controls, with the 1 mg cream and patch outperforming a commercial dressing.

  Key resultWound healing improved from 63.5 up to 81.81% in treatment groups vs the negative control (P < 0.05 and P < 0.001)

  Study details

  Studied

  Animals with experimental wounds

  Compared with

  Negative control (sham), vehicle patch/cream, and Comfeel positive control

  Main outcome

  Wound area, collagen density, angiogenesis, re-epithelialization

  Sample

  Animals randomly divided into seven groups; total number not stated

  Authors' conclusion

  Matrixyl cream and patch improved wound healing, with the 1 mg doses exceeding the commercial dressing, and the patch gave higher re-epithelialization than the cream.

  Limitations

  Animal model; species and group sizes not stated in the abstract.

  DOI 10.1021/acsomega.2c02592PubMed 35874243Free full text
• ~ Mixed in vitroTissue Eng Regen Med · 2017

  Effect of Palmitoyl-Pentapeptide (Pal-KTTKS) on Wound Contractile Process in Relation with Connective Tissue Growth Factor and α-Smooth Muscle Actin Expression.

  Cells / labn = 3 for the quantified experiment

  In vitro study of Pal-KTTKS (0-0.5 uM) on fibroblast-to-myofibroblast transformation

  In fibroblast cultures, pal-KTTKS at 0.1 µM halved myofibroblast transformation (alpha-SMA-positive cells 75% vs 38.6%), but 0.5 µM had no significant effect; authors caution about balancing healing and pro-fibrotic effects.

  Key resultalpha-SMA-positive stress fibers fell twofold with 0.1 uM Pal-KTTKS (75 +/- 7.1 vs 38.6 +/- 16.1%, n = 3, p < 0.05); not significant at 0.5 uM

  Study details

  Studied

  Cultured fibroblasts and 3D collagen lattices

  Compared with

  Untreated fibroblasts

  Main outcome

  alpha-SMA-positive cells, CTGF, lattice contraction

  Authors' conclusion

  Pal-KTTKS at 0.1 uM reduced alpha-SMA expression and myofibroblast transformation in a dose-dependent manner; a balance between wound-healing and pro-fibrotic properties should be considered.

  Limitations

  In vitro with n = 3; effect lost at higher concentration.

  DOI 10.1007/s13770-016-0017-yPubMed 30603464Free full text
• ✓ Positive in vitroPharmaceutics · 2024

  Liposome Encapsulation of the Palmitoyl-KTTKS Peptide: Structural and Functional Characterization.

  Cells / lab

  In vitro formulation and collagen synthesis assay

  Mouse fibroblasts: liposome-delivered palmitoyl-KTTKS stimulated more collagen production than free peptide or 1 mM ascorbic acid; a formulation study, cells only.

  Study details

  Studied

  3T3-NIH fibroblasts

  Compared with

  Free pentapeptide; 1 mM ascorbic acid

  Main outcome

  Collagen and extracellular matrix synthesis

  Authors' conclusion

  Liposomal pal-KTTKS stimulated collagen production more than free pentapeptide and ascorbic acid, and liposomes could improve peptide stability and skin delivery.

  Limitations

  Cell culture; no human or in vivo skin data.

  DOI 10.3390/pharmaceutics16020219PubMed 38399273Free full text
  Figure 3
• ✓ Positive animalArch Dermatol Res · 2024

  Mesenchymal stem cell therapy using Pal-KTTKS-enriched carboxylated cellulose improves burn wound in rat model.

  Animalssize not reportedRandomizedDays 3, 7 and 14

  Randomized animal study: Vaseline gauze, carboxylated cellulose, pal-KTTKS-cellulose, or MSCs on pal-KTTKS-cellulose

  Rat burn wounds: dressings containing pal-KTTKS (with or without stem cells) healed better than Vaseline gauze, with more collagen and faster closure; the effect of the peptide alone is not separated from the cellulose dressing.

  Study details

  Studied

  Healthy male rats with burn wounds

  Compared with

  Vaseline gauze; cellulose dressing

  Main outcome

  Wound closure, inflammation, collagen deposition, angiogenesis

  Authors' conclusion

  Pal-KTTKS-enriched composites improved burn wound healing, best when combined with mesenchymal stem cells.

  Limitations

  Rat study; combined dressing/stem-cell product.

  DOI 10.1007/s00403-024-03082-1PubMed 38850353
• ~ Mixed in vitroMolecules · 2019

  The Effects of a Novel Series of KTTKS Analogues on Cytotoxicity and Proteolytic Activity.

  Cells / lab

  In vitro synthesis and screening of KTTKS analogues

  Lab study of new KTTKS analogues: palmitoyl versions were the strongest plasmin inhibitors; none was cytotoxic to fibroblasts, but the three that boosted cell growth showed no concentration-dependent effect on collagen or DNA synthesis.

  Study details

  Studied

  Fibroblasts and purified proteases

  Main outcome

  Protease inhibition, cytotoxicity, collagen and DNA biosynthesis

  Authors' conclusion

  Palmitoyl peptides were the most active plasmin inhibitors and none were cytotoxic; no concentration-activity relationship was seen in the collagen and DNA assays.

  Limitations

  In vitro; tests analogues rather than only Matrixyl.

  DOI 10.3390/molecules24203698PubMed 31618846Free full text
  Figure 1

Reported side effects

No adverse-event data for Matrixyl on its own were found in the published abstracts.

✓ positive · ✗ negative · ~ mixed · ? inconclusive, judged on each paper's own main outcome. Grades: A strong human evidence → D little or none. Papers and verdicts are drawn from PubMed, Europe PMC and Russian journals (CyberLeninka); not medical advice.