Injectable crosslinked recombinant collagen nanofiber implants enable robust regenerative repair of photoaged skin

Abstract

Chronic ultraviolet (UV) exposure drives skin photoaging by accelerating collagen degradation, disrupting extracellular matrix (ECM) organization, and impairing barrier function. Although recombinant collagens offer safety advantages over animal-derived counterparts, their limited self-assembly capability and inadequate structural stability restrict their therapeutic potential. Here, we develop injectable tetrakis(hydroxymethyl)phosphonium chloride (THPC)-crosslinked self-assembled recombinant type I collagen (SARCI) nanofibers with tunable crosslinking densities for the regenerative repair of photoaged skin. THPC-mediated crosslinking markedly enhanced the thermal stability, mechanical rigidity, and enzymatic resistance of the nanofibers. In vitro, all THPC-crosslinked SARCI formulations significantly promoted fibroblast migration, proliferation, and differentiation. In a UV-induced photoaging mouse model, THPC-crosslinked SARCI demonstrated excellent biocompatibility and effectively restored epidermal structure, increased dermal density, improved barrier integrity, and promoted robust collagen regeneration. Transcriptomic analysis further suggested that THPC-crosslinked SARCI mitigates UV-induced ECM degradation by modulating MAPK signaling and maintaining tissue homeostasis. Collectively, these findings establish THPC-crosslinked SARCI as a structurally robust, highly biocompatible, and functionally stable recombinant collagen implant with strong translational potential for the treatment of photoaged skin.