Kill Two Birds with One Stone: Dual‐Metal MOF‐Nanozyme‐Decorated Hydrogels with ROS‐Scavenging, Oxygen‐Generating, and Antibacterial Abilities for Accelerating Infected Diabetic Wound Healing

Diabetic wounds tend to develop into nonhealing wounds associated with the complex inflammatory microenvironment of uncontrollable bacterial infection, reactive oxygen species (ROS) accumulation, and chronic hypoxia. Damaged blood vessels hinder metabolic circulation, aggravating hypoxia, and ROS accumulation and further exacerbating the diabetic wound microenvironment. However, existing treatments with a single functionality have difficulty healing complicated diabetic wounds. Therefore, developing an integrative strategy to improve the hostility of the diabetic wound microenvironment is urgently needed. Herein, multifunctional genipin (GP)‐crosslinked chitosan (CS)‐based hydrogels decorated with the biomimetic metal–organic framework (MOF)‐nanozymes and the natural antibacterial agent chlorogenic acid (CGA), which is named MOF/CGA@GP‐CS (MCGC), are prepared. With catalase (CAT)‐like activity, these dual‐metal MOF‐nanozymes are promising bioreactors for simultaneously alleviating ROS accumulation and hypoxia by converting elevated endogenous H2O2 into dissolved oxygen in diabetic wounds. In addition, the other component of natural polyphenolic CGA acts as a mild antibacterial agent, efficiently inhibiting wound infection and avoiding antibiotic resistance. Impressively, the MCGC hydrogels accelerate infected diabetic wound healing by eliminating oxidative stress, increasing oxygenation, and reversing bacterial infection in vivo. In this work, an effective strategy based on multifunctional hydrogel wound dressings is successfully developed and applied in diabetic wound management. The metal‐organic framework (MOF)‐nanozyme‐decorated hydrogel with injectable, adhesive, and self‐healing properties, named MOF/CGA@GP‐CS (MCGC), is constructed. The antibacterial hydrogel exhibits nanozyme‐mediated catalase (CAT)‐like performance, simultaneously facilitating reactive oxygen species (ROS)‐scavenging and oxygen‐generation in infected diabetic wounds. Promisingly, the MCGC hydrogel significantly promotes wound closure, improves collagen deposition, and alleviates inflammation for accelerating infected diabetic wound healing in vivo.