Bienzymatic Cascade Reaction-Mediated One-Pot Xyloglucan/Chitosan Hydrogel with Antimicrobial, Hemostatic, and Angiogenic Properties for Burn and Diabetic Wounds Repair

Chronic wounds present clinical challenges due to delayed healing, infection, and immune dysfunction. Most hydrogel dressings rely on crosslinking agents with potential adverse effects. This study introduces a one-pot, dual-crosslinked hydrogel fabricated via a bienzymatic cascade system using chitosan modified with phenol and arginine groups (CPA), xyloglucan (XG), horseradish peroxidase, and galactose oxidase (GalOx). The GalOx oxidizes XG to generate aldehydes, which form Schiff base bonds with the amino groups of CPA, creating the first gel network and releasing H2O2. The phenol groups in CPA are then catalyzed by H2O2 and HRP to form covalent bonds, establishing the second network. The hydrogel exhibits excellent mechanics, shear-thinning, self-healing, injectability, antimicrobial activity, angiogenesis promotion, and hemostatic properties. It shows superb biocompatibility and accelerates wound healing in burn and diabetic mouse models, outperforming commercial products. This hydrogel is a promising dressing for chronic wound therapy.