Enzyme-mediated multifunctional self-healing lysozyme hydrogel for synergistic treatment of chronic diabetic wounds

Self-healing hydrogels have attracted significant attention in chronic diabetic wound healing due to their potential to minimize the risk of secondary infections caused by joint movement or dressing rupture. Herein, a multifunctional self-healing hydrogel mediated utilizing an enzyme-triggered cascade reaction based on dynamic imine bonds was designed. The hydrogel employs three enzymes: lysozyme (LYZ), glucose oxidase (GOx), and catalase (CAT), as building blocks. GOx catalyzes the conversion of glucose and 1-thio-β-d-glucose (β-GlcSH) into hydrogen peroxide (H₂O₂), gluconic acid (GA), and hydrogen sulfide (H₂S). Subsequently, CAT eliminates H₂O₂, protecting the imine bonds from oxidative damage. The acidic environment created by GA decreases the pH and regulates the crosslinking density of imine bonds, enhancing the self-healing capability and porosity of the hydrogel. This feature enables the sustained release of the drug rosuvastatin calcium (RCa) to promote endothelial cell migration and vascular regeneration. Combined with the antioxidative and anti-inflammatory effects of released H₂S gas and the antibacterial properties of lysozyme, this hydrogel exhibits promising therapeutic efficacy for the synergistic treatment of chronic diabetic wounds.