Dual-dynamic carboxymethyl chitosan hydrogel with photothermal properties and programmed radical/NO release properties for enhanced healing of infected wounds

Bacterial-infected wound healing still faces substantial challenges, including multidrug-resistance, uncontrollable bleeding, long-term inflammation, and impaired angiogenesis. However, current treatment strategies cannot meet the complex demands of skin wound healing. We here developed a dual dynamic CFP hydrogel based on Schiff base and borate ester bonds between carboxymethyl chitosan (CMCS), polyvinyl alcohol (PVA), and 2-formylphenylboronic acid (2-FPBA). Meanwhile, customized L-arginine/epigallocatechin-3-gallate/ferric ion (EAF) nanoparticles and the thermal-labile 2,2'-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH) initiator were embedded into the CFP hydrogel for healing infected wound. The EAF/A/CFP hydrogel could create a protective barrier on bleeding wounds and reduced blood loss. Under 808 nm laser irradiation, the hydrogel exhibited excellent photothermal, alkyl free radical production ability, and continuous release of nitric oxide (NO) to effectively eradiate the bacteria, including mature biofilms. In addition, NO release regulated inflammation and promoted angiogenesis, thus significantly promoting the wound healing. The EAF/A/CFP hydrogel successfully achieved rapid wound repair in a full-thickness skin wound model. Consequently, this study provides a potential dressing for comprehensive management of skin wound healing.