While matrikines from damaged tissue increase inflammation, matrikines from adipose mesenchymal stem cells (ADSCs) and fibroblasts (FBs) reduce inflammation and rebuild the matrix without fibrosis.

The global aging of populations has driven a steady rise in skin pathologies — including skin cancer, inflammatory dermatoses, photoaging, and chronic wounds — imposing a growing burden on healthcare systems and quality of life (Flohr & Hay, 2021). Addressing these conditions requires not only early detection, effective therapeutic strategies tailored to the aging skin environment, but most importantly, improved prevention strategies.

Central to the pathology of most skin conditions, indeed, most tissues (Maguire, 2018), is the extracellular matrix (ECM) — a dynamic network of proteins, proteoglycans, and associated molecules that provides structural support, maintains tissue integrity, and governs cell migration, proliferation, differentiation, and survival (Bhat and Bissell, 2014; Kular et al., 2014). The ECM is maintained through continuous, protein- and tissue-specific cycles of synthesis and degradation; disruption of this homeostasis underlies both pathological conditions and the aging process itself (Iozzo & Gubbiotti, 2018; Statzer et al., 2023).

Enzymatic degradation of ECM macromolecules liberates small bioactive peptides known as matrikines, which exert broad (patho)physiological effects on cell signaling, behavior, and tissue homeostasis. The term was introduced by Maquart et al. to describe peptides released by partial proteolysis of ECM components that retain the capacity to regulate cellular activity (Maquart et al., 2004). I’ve adopted the expanded definition of Gaggar and Weathington, which requires matrikines to satisfy three criteria: (1) they are derived from larger ECM macromolecules; (2) they are generated by enzymatic, chemical, or other cleavage — and can therefore be produced ex vivo and introduced therapeutically; and (3) they display intrinsic bioactivity on cells or cellular receptors, independent of the properties of their parent molecule (Gaggar & Weathington, 2016).

In skin, matrikines have been identified across a range of pathological contexts, including melanoma, wound healing, inflammatory disease, and aging (Jariwala et al., 2022; Sivaraman & Shanthi, 2018). Their therapeutic potential is substantial: matrikines have been shown to accelerate wound closure by promoting cell migration and ECM deposition, attenuate inflammation through modulation of cytokine production, and counter skin aging by stimulating collagen synthesis. However, during chronic injury, uncontrolled release of matrikines can drive fibrotic cascades by activating fibroblasts and triggering the abnormal deposition of collagen, worsening tissue scarring. Cutaneous matrikines as produced in damaged skin is a complex process, encompassing their ECM precursors, pharmacological activities, roles in skin pathology, and prospects for therapeutic application. But overall, these matrokines produced in damage skin are, of course, damage signals. As such, they differ from the marix building molecules, including matrikines, released from stem cells resident in the skin. For example, the tripeptide Proline-Glycine-Proline (PGP) is a collagen-derived matrikine that has classically been described as a neutrophil chemoattractant; meaning it is an inflammatory matrikine. Conversley, the molecules released from skin derived stem cells contained in NeoGnesis S2RM, are anti-inflammatory (Maguire et al, 2026). 

Matrikines produced from the proteins released from stem cells is a developmental process, not a damage signaling process. These molecules, including matrikines or their precursors (such as procollagen), released from skin stem cells are anti-inflammatory, which is unlike the matrikines produced in damaged skin.

A buzz has been created for matrikines in skincare, but remember, matrikines produced by damaged matrix in the skin are on the whole pro-inflammatory. However, the secretome from ADSCs and FBs, as used in NeoGenesis’ S2RM technology, has been found to be anti-inflammatory and does so by containing a plethora of proteins and microproteins, all of which contain mutliple peptide sequences, including matrikines. Rebuilding the skin’s matrix is critical to skin health, and the best products on the market to help rebuild the matrix and reduce fibrosis are those that contain the S2RM – Recovery, Skin Serum, and Booster from NeoGenesis. Using NeoGenesis’ S2RM-based products can prevent inflammation and scarring that occurs as the skin ages and is bombarded by inflammatory damage-associated matrikines, promoting skin longevity.