Multifunctional antibiotics-free hydrogel dressings with self-regulated nitric oxide-releasing kinetics for improving open wound healing

Healing of large open wounds remains a major challenge in clinics due to the high risk of bacterial infection and slow healing rates, while excessive use of antibiotics would cause enhanced antibiotic resistance and reduced biocompatibility. Herein, we developed a multifunctional hydrogel dressing (GCNO) through embedding nitrosothiol-conjugated chitosan into a crosslinked gelatin methacrylate (GelMA) network via hydrogen bonding, which presented self-regulated nitric oxide (NO) release kinetics for temporally controlled bacterial elimination and wound repair. At early stages after implantation, the positively charged chitosan molecules of the GCNO hydrogel precursors and release of a high level of NO from the GCNO hydrogel demonstrated effective coordinated antimicrobial capability, thus preventing wound infection in the early stages of healing. While at later stages of wound healing, the hydrogel could sustainably release low levels of NO to stimulate the proliferation and migration of fibroblasts and endothelial cells, leading to accelerated angiogenesis and cell deposition at the wound area. GCNO hydrogels exhibited anti-bacterial and wound repair performance with excellent biocompatibility and biosafety. Overall, this antibiotic-free GCNO hydrogel could demonstrate self-adaptive NO release profiles to prevent bacterial infection in early stages of wound healing while accelerating skin regeneration at later stages, which may offer new insights for the clinical management of large open wounds in clinics.