Functionalized transdermal collagen mimetic peptides for efficient repair of subacute aged skin
Abstract
Skin aging compromises both aesthetic appearance and barrier function, presenting significant challenges for dermal regeneration. Collagen represents a crucial target for anti-aging interventions; however, they suffer from risk of virus transmission, large molecular weight and difficulty in transdermal transmission. Herein, we designed a series of transdermal collagen mimetic peptides (TSTPs) and a functionalized transdermal collagen mimetic peptide for efficient repair of subacute aged skin. The TSTP-2, with the sequence (GPO)8KLPVM, was identified as the optimal peptide according to its superior biocompatibility and skin permeability. Mechanistic analysis indicated TSTP-2 improved transdermal delivery by perturbing skin lipids, engaging with keratin proteins, and altering hydration dynamics. The functionalized transdermal collagen mimetic peptide (TNC), engineered through GFOGER incorporation into TSTP-2, exhibited a stable triple-helical structure, effective transdermal delivery and high biological activity, significantly promoting fibroblast proliferation, adhesion, migration, and myofibroblast differentiation. Combo evaluation and histological analysis further revealed that TNC contributed to the repair of subacute aged skin by enhancing epidermal thickness, stimulating collagen/elastic fiber regeneration, improving hydration, and reducing oxidative stress. The functionalized transdermal collagen mimetic peptide represents an alternative strategy for collagen transdermal delivery, demonstrating potential applications in skin rejuvenation and regenerative medicine.