Injectable Hydrogel Based on Defect-Rich Multi-Nanozymes for Diabetic Wound Healing via an Oxygen Self-Supplying Cascade Reaction

Diabetic wound healing remains challenging owing to the risk for bacterial infection, hypoxia, excessive glucose levels, and oxidative stress. Glucose-activated cascade reactions can consume glucose and eradicate bacteria, avoiding the direct use of hydrogen peroxide (H2O2) and wound pH restriction on peroxidase-like activity. However, the anoxic microenvironment in diabetic wounds impedes the cascade reaction due to the oxygen (O-2) dependence of glucose oxidation. Herein, defect-rich molybdenum disulfide nanosheets loaded with bovine serum albumin-modified gold nanoparticle (MoS2@Au@BSA NSs) heterostructures are designed and anchored onto injectable hydrogels to promote diabetic wound healing through an O-2 self-supplying cascade reaction. BSA decoration decreases the particle size of Au, increasing the activity of multiple enzymes. Glucose oxidase-like Au catalyzes the oxidation of glucose into gluconic acid and H2O2, which is transformed into a hydroxyl radical (center dot OH) catalyzed by peroxidase-like MoS2@Au@BSA to eradicate bacteria. When the wound pH reaches an alkalescent condition, MoS2@Au@BSA mimicks superoxide dismutase to transform superoxide anions into O-2 and H2O2, and decomposes endogenous and exogenous H2O2 into O-2 via catalase-like mechanisms, reducing oxidative stress, alleviating hypoxia, and facilitating glucose oxidation. The MoS2@Au@BSA nanozyme-anchored injectable hydrogel, composed of oxidized dextran and glycol chitosan crosslinked through a Schiff base, significantly accelerates diabetic wound healing.