Innovative MRSA-infected wound repair strategy: NIR-triggered controllable NO releasing from plant extracts quercetin composite chitosan/hyaluronic acid hydrogel

Bacterial infection reduces quality of wound healing and even cause severe complications, but most current dressings adopt single antibacterial mode showed limited effectiveness. Herein, a plant extract quercetin (Que) composite chitosan/hyaluronic acid hydrogel (named CBCQ) with near-infrared (NIR) triggered controllable NO releasing was developed for efficient photothermal therapy/nitric oxide (PTT/NO) synergistic antibacterial and wound healing. Specifically, CBCQ hydrogel with chemical/physical crosslinked network was fabricated via host-guest interaction, metal coordination and Schiff base reaction. It exhibited porous structure, excellent injectability, self-healing, adhesion, antioxidant, and biocompatible properties suitable for wound dressings. Notably, superior PTT effect generated from Que-Fe 3+ has been demonstrated, which served as a photothermal switch for the controllable NO release, thereby enable to utilize the physiological functions of NO at different concentrations, improving antibacterial efficiency by integrating PTT and NO benefits, and further allowing sustained antibacterial through Que when NIR was off. Importantly, CBCQ hydrogel achieved better healing of skin incision than commercial 3M medical glue and Film, and significantly improved the healing rate and quality of Methicillin-resistant Staphylococcus aureus (MRSA) infected wound by efficient and sustained antibacterial activity, inhibiting inflammation, and promoting collagen deposition and angiogenesis, highlighting its promising application in skin incisions and infected full-thickness skin wounds.