A Strategy for Diabetic Wound Healing: Electrostatic Adsorption of Structural Stability Drugs with Antibacterial, Anti‐inflammatory, and Angiogenic Effects

Abstract Structural stability drugs (SSDs) hold great promise for diabetic infected wound (DIW) therapy, yet challenges remain in achieving efficient delivery and sustained retention. This study presents a self‐healing, tissue‐adhesive hydrogel that leverages electrostatic adsorption to load SSDs offering advantages over conventional encapsulation or covalent strategies, including improved drug loading efficiency, preserved bioactivity by avoiding chemical modification, and prolonged release. Hyaluronic acid (HA) is first sulfonated with negatively charged sulfate groups and then modified with aldehyde and hydrazide groups to create HA–CHO–SO ₃ and HA–NHNH ₂ –SO ₃ precursors, which form dynamic acylhydrazone‐crosslinks upon co‐extrusion, providing self‐healing capacity via Schiff base reactions. Moreover, through electrostatic adsorption enhances SSDs (TGFβ1 and BBR) loading and retention. In a rat DIW model, the hydrogel's aldehyde groups bond with amino groups in the skin tissue, enhancing wound adhesion. Within the negatively charged wound environment, TGFβ1 and BBR are gradually released and trapped at the wound site through electrostatic interactions, enabling prolonged retention under exudative and mechanically disturbed wound conditions. Experimental results demonstrate that BBR effectively reduced bacterial load and inflammation, while TGFβ1 facilitated angiogenesis, accelerating wound healing by promoting epithelialization and collagen deposition. Overall, this novel hydrogel offers a promising strategy for delivering SSDs to enhance DIW treatment.