Catalase-like Nanozyme-Hybrid Hydrogels Utilizing Endogenous ROS as an Oxygen Source To Synergically Regulate Oxidative Stress and Hypoxia for Enhanced Diabetic Wound Healing.

Abstract

High levels of reactive oxygen species (ROS) and hypoxia in diabetic wounds significantly hinder the healing process. In this work, a kind of catalase-like nanozyme-hybrid hydrogel was developed to explore the potential of harnessing endogenous excessive ROS as an oxygen source to synergistically regulate oxidative stress and hypoxia, thereby enhancing diabetic wound healing. The hydrogels exhibited rapid degradation and controlled release of ferrihydrite nanozymes in response to oxidative stress, which continuously catalyzed the decomposition of H₂O₂ to generate oxygen, effectively scavenging ROS and reducing the risk of local oxygen toxicity. The hydrogels relieved intracellular oxidative stress and the hypoxic microenvironment simultaneously in vitro. The hydrogel dressings effectively inhibited oxidative damage at wound sites, promoted epidermis formation and collagen deposition, and significantly accelerated wound healing in db/db mice. Therefore, the catalase-like nanozyme-hybrid hydrogels represent a promising strategy for diabetic wound dressings, addressing both oxidative stress and hypoxia to improve healing outcomes.