Incorporating copper-based nanosheets into an injectable self-healing hydrogel enables superb repair of infected diabetic wound

Continuous bleeding, bacterial infection, oxidative stress, and vascular damage within a diabetic wound microenvironment necessitate the development of multifunctional dressings that match the complex physio-logical process of skin healing. Herein, copper-tannic acid (CuTA) nanosheets were first synthesized by chelating copper ions with tannic acid (TA). These nanosheets were subsequently integrated into an injectable self-healing hydrogel comprising methacrylic anhydride-modified gelatin (GelMA), cationic guar gum (CG), and borax. Through free-radical polymerization as well as hydrogen and borate ester bonds formation, we fabricated an acidic and highly reactive oxygen species (ROS)-responsive composite hydrogel named GGB-CT, which exhibited remarkable hemostasis and adhesion. With responsive decomposition of GGB-CT, the released CuTA efficiently scavenged excess ROS as well as effectively killed bacteria by inhibiting arginine synthesis, blocking the tricarboxylic acid cycle and inducing cuproptosis-like death in the tested microbes. In the later stages of wound healing, the composite hydrogel substantially promoted macrophage polarization and angiogenesis, thus accelerating the re-epithelialization of the wound area. Overall, this study proposes an innovative hydrogel for treating infected diabetic wounds and may inspire new thinking of high-performance hydrogels for biomedical applications.