The Human‐Like Collagen Alpha‐1 Type V Peptides Strengthen the Dermal Fiber Network and Improve the Regeneration Ability of Cells

BACKGROUND: Collagen, a major structural component of the skin, decreases with age and is associated with wrinkles, reduced elasticity, sagging, and dryness. While hydrolyzed or marine-derived collagens are widely used in cosmetics, advances in biotechnology have enabled the development of bio-collagen peptides. However, the role of collagen type V-derived peptides in skin biology remains largely unexplored. AIMS: In this study, we generated human-like collagen alpha-1 type V peptides (hCOLVp) and investigated their effects on skin-related parameters. PATIENTS/METHODS: COL5A1-derived peptides with optimized sequences were generated, and a single candidate was identified through screening. Protein expression of collagen types I, III, XVII, and laminin 5 was evaluated in human dermal fibroblasts or keratinocytes. A collagen gel contraction assay and SEM-based microstructural analysis were performed. Finally, a reconstructed human full-thickness skin (RS) model was used to assess peptide penetration and barrier-associated proteins. RESULTS: hCOLVp increased expression of collagen types I, III, XVII, and laminin 5. Treated collagen gels showed greater contractile force and higher fiber density than controls. In RS models, hCOLVp penetrated over time and was associated with increased collagen fibers and upregulated expression of involucrin and transglutaminase-1 (TGase-1), both related to barrier function. In a preliminary clinical trial, hCOLVp improved skin barrier properties, density, and elastic recovery. CONCLUSION: These findings suggest that hCOLVp contributes to strengthening dermal and epidermal structural networks, thereby supporting skin function and resilience.