Eco-engineered recombinant collagen III-PEG hydrogels with curcumin synergy for accelerated skin regeneration: A green crosslinking strategy in wound therapeutics.

The development of immunologically safe collagen-based hydrogels remains challenging due to risks associated with animal-derived collagens and toxic crosslinkers. Here, we report an eco-friendly hydrogel platform integrating recombinant humanized collagen type III (PCIII) expressed in Pichia pastoris with 4-arm PEG-SS via a one-step green crosslinking strategy. The engineered PEG-PCIII hydrogels exhibit tunable mechanics, enzymatic degradability, and rapid self-gelation through amine-NHS ester conjugation, while curcumin loading endows it with adjustable antioxidant activity. In vivo evaluation in a full-thickness skin defect model demonstrates that the curcumin-loaded hydrogel (PEG-PCIII-cur) orchestrates a pro-regenerative microenvironment, significantly enhancing VEGF-mediated angiogenesis, fibroblast-driven granulation tissue formation, and hair follicle neogenesis while optimizing collagen I/III stoichiometry for functional repair. Demonstrating accelerated functional wound repair with optimized collagen deposition in vivo, this strategy provides a highly promising platform integrating biosafety, structural resilience, and oxidative stress mitigation for future development in refractory wound management.