Synergistic Immunomodulation and Angiogenesis‐Driven Microenvironment Remodeling via Bioactive Hydrogel/Nanofiber Composites for Enhanced Infectious Wound Healing

ABSTRACT

Numerous types of wounds are at risk for infection, such as burn wounds, traumatic wounds, surgical wounds, chronic ulcer wounds, and radiologic wounds. The repair of infectious wounds depends on specific microenvironments, including moderate hydration, reactive oxygen scavenging, antimicrobial, anti‐inflammatory, and angiogenic conditions. To effectively promote the repair of infectious wounds and reduce the risk of infection spread, we developed a multifunctional bilayer wound dressing (MBWD) that simultaneously meets these criteria. The inner layer (DMOG@PCL/ASC) consists of a polycaprolactone (PCL)/fish collagen (ASC) nanofiber decorated with coaxial microparticles containing dimethyloxalylgcine (DMOG). The three‐dimensional pore structure of nanofibers offers numerous adhesion sites for cells, and the gradual release of DMOG can promote angiogenesis. The outer layer consists of a glycidyl methacrylate‐modified carboxymethyl chitosan hydrogel loaded with cerium oxide nanozymes (M‐CMCS/CeO ₂ ). This M‐CMCS hydrogel provides a moist microenvironment and exhibits antimicrobial properties. The localized release of CeO ₂ can deliver antioxidant effects, combat microbes, and modulate inflammation. In vivo studies confirmed that the MBWD dressing can enhance the healing of infectious and diabetic wounds by providing rapid antimicrobial, anti‐inflammatory, and pro‐angiogenic effects. Therefore, this combined system of nanofibers and hydrogels, each loaded with specific functional components, offers an effective strategy for treating infectious wounds.