Tailored Metal-Phenolic Network with Hypoglycemic Polyphenol for Promoting Diabetic Wound Healing

Diabetic foot ulcer is a common and serious complication of diabetes, with a high risk of amputation, recurrence, and mortality. Aiming at the characteristics of diabetic wounds and based on the result of network pharmacology, a tailored ligand cyanidin-3-O-glucoside (C3G) was selected to construct a metal-phenolic network (CM) through the self-assembly reaction with manganese ions. CM integrates the pharmacological advantages of C3G in antidiabetes and the anti-inflammatory activity of metal-phenolic networks by simulating the metal coordination structure of antioxidant enzymes. Reasonably, the wound areas of db/db mice with CM treatment rapidly decreased to 3.06% at day 14, accompanied by the improvement of tissue microenvironment. Mechanism investigation indicated that CM can not only reduce inflammation activation and immunoreaction but also increase gene transcripts in glucose metabolism, response to hypoxia, and angiogenesis. It is believed that this work opens a way for designing disease-specific metal-phenolic networks, and the CM with high biosafety promotes the clinical treatment of diabetic wounds.