Intelligent response hydrogel based on choline phosphorylated chitosan programmed repair of infected wounds

Abstract The healing of infected wounds is a formidable clinical challenge that demands advanced biomaterials capable of simultaneously eradicating pathogens and orchestrating the complex regenerative process. Herein, we engineered an immunomodulatory and angiogenic multifunctional hydrogel dressing by integrating choline phosphorylated chitosan (CS-MCP) with tetracycline-loaded polydopamine nanoparticles (PDA@TH NPs) for the programmed healing of infected wounds. This composite hydrogel demonstrates on-demand, spatiotemporally controlled therapeutic responses. Under near-infrared (NIR) irradiation, it enables synergistic bactericidal activity through photothermal effects and triggered antibiotic release. Moreover, the system exhibits pH-responsive drug release behavior, specifically targeting the acidic microenvironment of infected tissues. Beyond its potent antibacterial function, the hydrogel actively promotes regenerative processes. In vitro, CS-MCP markedly enhanced the adhesion, proliferation and tube formation of human umbilical vein endothelial cells, demonstrating potent pro-angiogenic effects. Furthermore, the polydopamine nanoparticles effectively scavenged reactive oxygen species (ROS), attenuating oxidative stress and inducing M2 macrophage polarization to foster an immunoregulatory microenvironment conducive to tissue repair. In a rat model of Staphylococcus aureus-infected full-thickness skin defects, the hydrogel significantly accelerated wound healing by comprehensively modulating the entire regeneration cascade: eliminating infection, mitigating inflammation, promoting angiogenesis, and enhancing collagen deposition. This study presents a novel immune-engaging and pro-regenerative strategy, representing a highly promising platform for the treatment of refractory infected wounds.