Matrikines are a large and somewhat loosely defined group of peptides and small proteins, encompassing both endogenous signalling factors important in wound healing and tissue remodeling, and synthetically produced versions of these along with related analogues and derivatives, which are used mainly for cosmetic applications as well as for scientific research and with some medical indications.[1][2][3][4][5][6][7][8][9][10][11][12][13]
There are over 100 peptides which have been claimed as falling within this group, though most of them have relatively little published research and only a dozen or so such compounds are widely known and well characterised.[14] Most compounds referred to as matrikines are synthetic versions of peptide fragments 2-6 amino acids in length which are found in connective tissue proteins such as collagen, elastin, fibronectin and laminin, and were originally isolated as products of the enzymatic hydrolysis of these proteins. However there are also other peptide fragments with similar activity which are commonly included in this group, despite not being derived from connective tissue proteins. Larger protein fragments cleaved from the full length protein such as arresten, canstatin and tumstatin also have similar functions and may be grouped along with the smaller peptide matrikines.
Function
Administration of these peptides stimulates cells in the skin such as fibroblasts to synthesise more of these proteins, and is claimed to facilitate skin repair and wound healing and to have an anti-wrinkle and anti-aging effect. They are administered topically as skin creams, or sometimes by subcutaneous injection or microneedling. It is important to note that matrikines are a diverse class of signalling peptides which do not all have the same spectrum of activity; certain members of the family such as hexapeptide-12 actually have a primarily pro-aging effect and are used in research into the aging process rather than as ingredients of anti-aging skin creams. Other matrikines can have anti-aging effects at low concentrations but promote carcinogenesis and tumor growth at higher levels, so appropriate dosage control is critical.
Research and applications
Since these peptides are used primarily for cosmetic applications which require only limited safety testing and have no requirement for proof of efficacy, much research into these peptides has been published in self-published sources such as patent applications, or in open-access journals which are generally regarded as low-quality sources due to the limited scope of peer review. This has meant that the claimed efficacy of these peptides has historically been treated with skepticism by the mainstream scientific community and regarded as marketing hype which has not been proven by rigorous scientific research. In recent years however, increasing evidence has accumulated to support the claimed activity of at least some of the matrikine peptides, along with investigation of these molecules for potential clinical applications such as treatment of arthritis and tendinopathy, and this has led medicines regulators in some jurisdictions such as Australia and New Zealand to view certain peptides from this group as medicines, and consequently ban them by classifying them as prescription medicines which are not actually available for prescription. In most parts of the world however these peptides are still classified as cosmetics and can be sold with relatively few restrictions, and they are widely used in countries such as Japan, China, South Korea, the United States and in Europe.
↑Grahovac J, Wells A. Matrikine and matricellular regulators of EGF receptor signaling on cancer cell migration and invasion. Lab Invest. 2014 Jan;94(1):31-40. doi:10.1038/labinvest.2013.132PMID24247562
↑Ricard-Blum S, Vallet SD. Fragments generated upon extracellular matrix remodeling: Biological regulators and potential drugs. Matrix Biol. 2019 Jan;75-76:170-189. doi:10.1016/j.matbio.2017.11.005PMID29133183
↑Kisling A, Lust RM, Katwa LC. What is the role of peptide fragments of collagen I and IV in health and disease? Life Sci. 2019 Jul 1;228:30-34. doi:10.1016/j.lfs.2019.04.042PMID31004660
↑Jariwala N, Ozols M, Bell M, Bradley E, Gilmore A, Debelle L, Sherratt MJ. Matrikines as mediators of tissue remodelling. Adv Drug Deliv Rev. 2022 Jun;185:114240. doi:10.1016/j.addr.2022.114240PMID35378216
↑Rapp AE, Zaucke F. Cartilage extracellular matrix-derived matrikines in osteoarthritis. Am J Physiol Cell Physiol. 2023 Feb 1;324(2):C377-C394. doi:10.1152/ajpcell.00464.2022PMID36571440
↑Chen K, Xu M, Lu F, He Y. Development of Matrix Metalloproteinases-Mediated Extracellular Matrix Remodeling in Regenerative Medicine: A Mini Review. Tissue Eng Regen Med. 2023 Aug;20(5):661-670. doi:10.1007/s13770-023-00536-xPMID37160567
↑Revert-Ros F, Ventura I, Prieto-Ruiz JA, Hernández-Andreu JM, Revert F. The Versatility of Collagen in Pharmacology: Targeting Collagen, Targeting with Collagen. Int J Mol Sci. 2024 Jun 13;25(12):6523. doi:10.3390/ijms25126523{{doi}}: unflagged free DOI (link)PMID38928229
↑Ostadi Y, Khanali J, Tehrani FA, Yazdanpanah G, Bahrami S, Niazi F, Niknejad H. Decellularized Extracellular Matrix Scaffolds for Soft Tissue Augmentation: From Host-Scaffold Interactions to Bottlenecks in Clinical Translation. Biomater Res. 2024 Sep 6;28:0071. doi:10.34133/bmr.0071PMID39247652
↑van Walraven N, FitzGerald RJ, Danneel HJ, Amigo-Benavent M. Bioactive peptides in cosmetic formulations: Review of current in vitro and ex vivo evidence. Peptides. 2025 Nov;193:171440. doi:10.1016/j.peptides.2025.171440PMID40946970
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