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

Abstract

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.