Y326: A highly stable and bioactive substitute for animal-derived collagens in biomedical and cosmetic uses.

Collagen degradation is one of the marks of skin aging. Animal-derived collagens have been widely used to repair skin damage or anti-aging as medical devices in clinical application, but they still present a series of challenges, including resource shortage, pathogen contamination, immunogenicity, and batch inconsistency. To address this, 19 recombinant humanized collagen III variants were designed based on the sequence scanning of the triple-helical region (G168-C1196) of human collagen type III (UniProt ID: P02461), retaining critical adhesion sites (RGD and GER) and the GXY pattern. Variant 019 was selected for its highest adhesion activity and was further developed into a 6-repeated variant (Y88). Y88 was optimized subsequently by removing unstable residues identified by mass spectrometry analysis, yielding a stable, high-purity variant, Y326. Structural analysis confirmed Y326's triple-helical conformation; furthermore, functional assays demonstrated its ability to promote cell adhesion, migration, proliferation, and extracellular matrix synthesis in vitro. In a skin photoaging model, Y326 reduced wrinkles, improved hydration, increased dermis thickness and up-regulated endogenous collagen I expression. Thus, Y326 offers a promising substitute for animal-derived collagens in anti-aging applications.