Synergistic self-assembly and crosslinking yield a durable, bioactive, and injectable recombinant collagen implant for photoaging therapy

Abstract Sustained ultraviolet (UV) irradiation upregulates matrix metalloproteinases (MMPs) activity, exacerbates collagen degradation, and triggers inflammatory signaling, leading to extracellular matrix (ECM) disorganization and skin photoaging. While animal-derived collagens are widely used in clinical applications, their immunogenicity and batch variability limit safety and consistency. Recombinant collagen provides a safer and more controllable alternative. However, poor fibrillogenesis, limited structural stability, and rapid enzymatic degradation hinder long-term performance. Here, we developed an injectable recombinant collagen nanofiber implant (B-SARCI) through the synergistic integration of molecular self-assembly and mild 1,4-butanediol diglycidyl ether (BDDE) crosslinking. This dual strategy preserves excellent injectability while simultaneously enhancing thermal stability, and enzymatic resistance. B-SARCI improved fibroblast attachment and proliferation, promoted migration, and facilitated differentiation in vitro. In a murine UV-induced photoaging model, B-SARCI restored dermal density, enhanced barrier function, and reduced transepidermal water loss (TEWL). Transcriptomic and histological analyses revealed upregulation of Col1α1 and Col3α1, suppression of MMP2, MMP3, and MMP9, and modulation of the JAK-STAT pathway via SOCS3 induction and IL-6 downregulation. Together, these findings demonstrate that B-SARCI re-establishes ECM homeostasis and attenuates inflammation, representing a durable, bioactive, and clinically translatable recombinant collagen implant for photoaged skin repair.