Specific Nanozyme‐Based Cascade Catalysis Hydrogel With Oxygen‐Self‐Supplying and ROS‐Scavenging Capacity for Efficient Diabetic Wound Healing

Diabetic wounds are characterized by impaired and delayed healing due to a pathological triad of hyperglycemia, excessive reactive oxygen species (ROS) accumulation, and persistent tissue hypoxia. Herein, a glucose-activated cascade catalysis oxygen-self-supplying hydrogel (M/G gel) is developed by co-embedding glucose oxidase (GOx) and a catalase-mimicking molybdenum-based specific nanozyme (MF) into a biocompatible chitosan/sodium alginate hydrogel matrix. The M/G gel system initiates a glucose-responsive cascade reaction: GOx oxidizes glucose to produce H2O2, the resultant and endogenous H2O2 is then selectively decomposed by MF into H2O and O2, enabling simultaneous glycemic control, ROS scavenging and hypoxia alleviation. In vitro studies demonstrate that MF exhibits potent antioxidant activity, sustained O2 generation, and promotes the cell migration. In vivo results disclose that M/G gel accelerates diabetic wound healing by facilitating M1-to-M2 macrophage polarization switch, reducing HIF-1α expression, enhancing CD31-mediated angiogenesis, and restoring extracellular matrix deposition. Moreover, the hydrogel system shows excellent biocompatibility and biosafety. This work presents a rationally engineered, self-regulated cascade catalysis platform with great potential for the treatment of diabetic wounds and other ROS- and hypoxia-related diseases.