Microenvironment‐adaptive nanodecoy synergizes bacterial eradication, inflammation alleviation, and immunomodulation in promoting biofilm‐associated diabetic chronic wound healing cascade

Abstract The presence of bacterial biofilms and the occurrence of excessive inflammatory response greatly imped the healing process of chronic wounds in diabetic patients. However, effective strategies to simultaneously address these issues are still lacking. Here, a microenvironment‐adaptive nanodecoy (GC@Pd) is constructed via the coordination and in situ reduction of palladium ions on gallic acid‐modified chitosan (GC) to promote wound healing by synergistic biofilm eradication, inflammation alleviation, and immunoregulation. During the weakly acidic conditions of the biofilm infection stage, GC@Pd serves as a nanodecoy to induce bacterial aggregation. Subsequently, through its oxidase‐like activity generating reactive oxygen species and the hyperthermia from photothermal effects, it effectively eliminates the biofilm. As the local microenvironment of diabetic wounds transitions to an alkaline inflammatory state, the enzyme‐like activity of GC@Pd adapts to catalase‐like activity, effectively eliminating reactive oxygen species at the site of inflammation. Additionally, GC@Pd could selectively capture pro‐inflammatory cytokines through Michael addition reactions. In vivo experiments and transcriptomic analysis confirmed that GC@Pd could accelerate the wound transition from inflammatory to proliferative phase by eliminating biofilm infection and reducing the inflammatory response, thus promoting diabetic chronic wound healing. The nanodecoy provides a potential therapeutic strategy for treating biofilm‐infected diabetic chronic wounds.