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

High glucose- and acid-responsive hydrogel with dynamic covalent bond solubilized with flavonoids (Gel-Flavonoids) is designed for diabetic wound healing. The Gel-Flavonoids adapt to irregular wound shapes and release antioxidants in high-glucose environments, effectively reducing reactive oxygen species. Demonstrating superior healing rates and whole-layer regeneration compared to commercial dressings, this system offers promising insights for advanced medical materials in wound care.

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.