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

Abstract

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 (H₂ O₂ ) and wound pH restriction on peroxidase-like activity. However, the anoxic microenvironment in diabetic wounds impedes the cascade reaction due to the oxygen (O₂ ) 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 O₂ 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 H₂ O₂ , which is transformed into a hydroxyl radical (•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 O₂ and H₂ O₂ , and decomposes endogenous and exogenous H₂ O₂ into O₂ 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.