A refractory wound healing hydrogel with integrated functions of photothermal anti-infection, superoxide dismutase mimicking activity, and intelligent infection management

Promoting refractory wound healing remains a challenging issue. Currently, dressings with intelligent infection management functions built on infection eradication and reactive oxygen species (ROS) scavenging abilities are lacking. In this study, an approach based on Cu2+-imidazole coordination cross-linked histidine grafted chitosan (CS-His) and carbon quantum dots (CQDs) was developed to engineer superoxide dismutase (SOD) mimicking centers with photothermal anti-infection and intelligent anti-infection abilities, beyond typical ROS scavenging activity. The cross-linked coordination network was further promoted with tanshinol-encapsulated ZIF-8 frameworks (ZIF-8@Ts) to achieve intelligent infection management behaviors. These designs generate a refractory wound-healing hydrogel with integrated functions of photothermal anti-infection, SOD mimicking activity, and intelligent infection management. In response to infection exacerbation, the SOD mimicking centers and ZIF-8@Ts nanoparticles could release CQDs for anti-infection and Ts for antioxidation, respectively. In vitro results revealed photothermal anti-infection, ROS scavenging, and intelligent infection management capacities of the hydrogel. These abilities promoted the M2 transformation of macrophages and rescued the inhibitory effect of infection on fibroblast proliferation and migration. The hydrogel exhibited high regenerative efficacy in a rat model of chronically infected diabetic wounds. These results demonstrated the immense potential of the intelligent hydrogel integrated with multifunctions for refractory wound healing.