Injectable self-assembled recombinant collagen nanofiber restores ECM homeostasis for photoaged skin repair.

Abstract

Photoaging, caused by chronic ultraviolet (UV) exposure, leads to extracellular matrix (ECM) degradation, impaired skin function, and visible signs of aging. While collagen-based implants offer therapeutic potential, most rely on animal-derived sources, posing risks of immunogenicity and pathogen transmission. Recombinant collagens overcome these limitations but often lack the ability to form native-like fibers. Herein, we report the first injectable, self-assembled recombinant type I collagen nanofiber (SARCI) implant for reversing photoaged skin damage. The SARCI implant exhibits excellent injectability, enhanced thermal and enzymatic stability, and low immunogenicity. In vitro, it significantly promotes fibroblast proliferation, migration, and myofibroblast differentiation, while inducing chondrogenic commitment of mesenchymal stem cells. In a UV-induced photoaging mouse model, SARCI restores ECM homeostasis, improves epidermal thickness, dermal density, hydration, and transepidermal water loss, and reduces oxidative stress. Transcriptomic analysis confirms that SARCI activates ECM-receptor interaction, PI3K-Akt, and focal adhesion signaling pathways. These findings establish SARCI as a safe and effective recombinant biomaterial for regenerative dermatology and photoaging intervention.