Self‐Healing Hydrogel Dressing with Solubilized Flavonoids for Whole Layer Regeneration of Diabetic Wound

Abstract Hydrogels are soft, tissue‐like materials that have great potential as wound dressings. However, most hydrogels are unsatisfactory in achieving whole‐layer regeneration of diabetic wounds due to the complex pathological microenvironment and irregular wound shapes. Here, a glucose‐responsive and self‐adaptive phenylboronic acid (PBA) hydrogel solubilized strong antioxidant flavonoids (Gel‐Flavonoids) is developed via dynamic borate bonds. The Gel‐Flavonoids system can spontaneously confirm to the irregular wound shape and release flavonoids in a high‐glucose microenvironment to effectively eliminate reactive oxygen species (ROS). The optimized Gel‐Flavonoids demonstrate remarkable efficacy in inhibiting inflammation and activating fibroblasts and endothelial cells through CD36‐activated lipid metabolism in macrophages and is significantly superior to commercial dressings (3M) in healing rate (> 93%, 14 days) and whole‐layer regeneration effect. This study obtained a multidimensional Gel‐Flavonoids system to effectively repair diabetic wounds, and reveal the underlying therapeutic mechanisms, offering a promising insight to guide the development of medical materials to treat diabetic wounds.