An injectable photo-crosslinking silk hydrogel system with biphasic release of BTXA and 5-Fu promotes scarless wound healing

Abstract

Hypertrophic scarring is characterized by excessive dermal fibrosis and irregular collagen metabolism, mediated by fibroblasts derived from keloids. This condition typically arises from improper wound healing after deep burns, trauma, or surgical procedures. Although intralesional injections of botulinum toxin type A and 5-fluorouracil are common clinical treatments, their effectiveness is often limited by temporary drug retention, insufficient penetration depth, and complications from repeated injections. To overcome these challenges, we developed an injectable composite hydrogel system, F@P-B-SilMA, to promote scarless wound healing. Systematic characterization revealed that this system undergoes rapid UV-initiated in situ polymerization and exhibits a three-dimensional porous microstructure. It also demonstrates excellent tissue adhesion and mechanical compliance, along with favorable rheological properties, and tunable degradation kinetics that align with the various phases of wound healing. These attributes collectively meet the essential criteria for advanced wound dressings. Comprehensive in vitro and in vivo evaluations confirmed the system's biocompatibility and its dual ability to accelerate wound closure while suppressing fibrotic proliferation. The injectable F@P-B-SilMA composite hydrogel system represents a promising therapeutic approach for clinical scar management, showcasing significant potential as a next-generation wound dressing for scarless tissue regeneration.