Recombinant humanized type III collagen promotes repair of acute UV-induced skin injury with attenuated oxidative stress and extracellular matrix remodeling

Recombinant humanized type III collagen was prepared as a bioactive macromolecule. • rS-Col III promoted fibroblast adhesion, proliferation, migration, and repair signaling. • rS-Col III alleviated UV-induced oxidative stress in cellular and zebrafish models. • Topical rS-Col III accelerated skin barrier recovery and collagen remodeling in mice. • Recombinant type III collagen shows promise for skin repair and regenerative applications. Ultraviolet (UV)-induced skin injury is characterized by excessive oxidative stress, inflammatory activation and extracellular matrix (ECM) disruption. Animal-derived collagen is limited by source-dependent heterogeneity, batch variability, and potential biosafety concerns. Here, we developed a molecularly defined recombinant human COL3A1-derived collagen-like protein, termed recombinant humanized type III collagen (rS-Col III), for the topical repair of acute UV-induced skin injury. Its engineered precursor enabled enhanced soluble expression in Escherichia coli , while the processed rS-Col III exhibited collagen-like triple-helical characteristics, consistent molecular mass and thermal behavior, good batch-to-batch reproducibility, and favorable short-term biocompatibility. In vitro, rS-Col III promoted fibroblast adhesion, proliferation, and migration, enhanced ECM-related gene and protein expression, and increased extracellular type I collagen deposition. Under UVA-induced oxidative stress, rS-Col III reduced intracellular reactive oxygen species and malondialdehyde levels while restoring superoxide dismutase activity. A cell-free ABTS assay further demonstrated modest intrinsic radical-scavenging capacity. Complementary zebrafish models showed that rS-Col III attenuated chemically induced oxidative stress and protected against UV-induced tissue injury. In an acute UV-injured mouse model, topically applied rS-Col III exhibited measurable local retention and superficial tissue distribution, improved skin hydration and barrier function, promoted epidermal and dermal structural recovery and collagen remodeling, and attenuated oxidative stress, inflammation, and matrix-degradation-associated changes. Collectively, these findings establish rS-Col III as a structurally defined and reproducibly produced collagen-like biomaterial with promising potential to support early repair of acute UV-induced skin injury through coordinated restoration of redox balance, inflammatory regulation, ECM homeostasis, and skin barrier function.