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

Abstract

Continuous bleeding, bacterial infection, oxidative stress, and vascular damage within a diabetic wound microenvironment necessitate the development of multifunctional dressings that match the complex physiological 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.