Closing the Vicious Cycle: A Multimodal Hydrogel Targeting Hyperglycemia, Oxidative Stress, and Infection in Diabetic Wounds

Abstract

Diabetic chronic wounds, characterized by a unique pathological microenvironment including persistent hyperglycemia, excessive reactive oxygen species (ROS), bacterial infection, and sustained inflammation, exhibit notoriously impaired and delayed healing processes. This study developed a multifunctional hydrogel therapeutic system (GO x @Zn‐MPN Gel), employing Pluronic F‐127 as the matrix and loaded with glucose oxidase (GO x ) and a zinc–metal–phenolic network (Zn‐MPN). This system promotes wound healing through a triple synergistic mechanism: GOx responds to the hyperglycemic environment, catalyzing glucose into gluconic acid and H 2 O 2 , thereby reducing local glucose concentration and pH; gallic acid (GA) released from the decomposing Zn‐MPN effectively scavenges excess ROS; and the concurrently released Zn 2+ provides sustained antibacterial action. In vitro characterization demonstrated that the material possesses pH‐responsive release, stable enzymatic activity, and excellent ROS scavenging capacity (with scavenging rates for DPPH and ·O 2 − as high as 81.2% and 48.3%, respectively). Animal experiments confirmed that this hydrogel significantly accelerates the healing of full‐thickness skin defects in diabetic mice. These findings highlight the considerable potential of the GOx@Zn‐MPN hydrogel as a dressing for diabetic wound treatment.