Microenvironment-responsive and NO sustained-release hydrogel accelerates infected wound healing by bacteriostasis and angiogenesis.

Infected wounds pose a significant clinical challenge due to persistent infection, chronic inflammation, insufficient angiogenesis, and compromised tissue regeneration. Nitric oxide (NO) has attracted considerable attention in infected wound healing recently. However, achieving microenvironment-responsive and sustained release of NO remains challenging. In this study, we develop a microenvironment-responsive sodium alginate (SAZA) hydrogel loaded with ZnO2 nanoparticles (NPs) and L-arginine (L-Arg). In the acidic microenvironment of infected wounds, ZnO2 NPs within SAZA hydrogel underwent hydrolysis to release H2O2 and Zn2+, and then H2O2 reacted with L-Arg in a cascade reaction to generate NO, conferring both responsive effectiveness and prolonged treatment benefits. Furthermore, the increased membrane permeability induced by Zn2+ facilitated the entry of NO into bacterial cells, promoting DNA damage and metabolic inhibition. Under this synergistic effect, SAZA hydrogel exhibited enhanced antibacterial activity. Meanwhile, SAZA hydrogel also facilitated cell migration and angiogenesis while demonstrating good biocompatibility. In vivo experiments further confirmed that SAZA hydrogel mitigated infection and inflammation in infected wounds of mice, and accelerated wound healing through enhanced angiogenesis and collagen deposition. By integrating strong antibacterial activity with improved tissue repair, this multifunctional hydrogel with NO sustained release offers a promising strategy for treating infected wounds.