Functionalized transdermal collagen mimetic peptides for efficient repair of subacute aged skin

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 the 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. TSTP-2, with the sequence (GPO)₈KLPVM, was identified as the optimal peptide according to its superior biocompatibility and skin permeability. Mechanistic analysis indicated that 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. The results of the DermaLab® Combo skin analyzer and histological analysis demonstrated that TNC promoted subacute aged skin repair by increasing epidermal thickness, stimulating collagen and elastic fiber regeneration, improving hydration, and reducing oxidative stress. The use of functionalized transdermal collagen mimetic peptides represents an alternative strategy for collagen transdermal delivery, showing potential applications in skin rejuvenation and regenerative medicine.