A Versatile Glycopeptide Hydrogel Promotes Chronic Refractory Wound Healing Through Bacterial Elimination, Sustained Oxygenation, Immunoregulation, and Neovascularization

Abstract Chronic refractory wounds have become a severe threat to public health and are characterized by repeated bacterial infections, persistent hypoxia, abnormal immune regulation, and obstruction of angiogenesis. However, current treatment strategies usually perform only one or two therapeutic functions and cannot satisfy the dynamic and complex demands of chronic wound healing. Herein, a versatile dynamic Schiff base and borate ester cross‐linked glycopeptide hydrogel is prepared from phenylboronic acid‐grafted ε‐polylysine (EPBA), epigallocatechin‐3‐gallate (EGCG), and oxidized alginate. Customized polydopamine‐coated honeycomb MnO 2 nanoparticles loaded with herb‐derived salvianolic acid B (PHMS) are embedded into the hydrogel before gelation. Under the distinct acidic and oxidative microenvironment of chronic refractory wounds, the hydrogel gradually dissociates, and the released EPBA effectively eliminates bacteria, while the released EGCG and PHMS eradicates reactive oxygen and nitrogen species, promotes M2 polarization of macrophages, and continuously generates oxygen. Then PHMS further disintegrates, and the released salvianolic acid B promotes angiogenesis through the PI3K/Akt pathway. The versatile glycopeptide hydrogel accelerates Staphylococcus aureus ‐infected diabetic cutaneous wound repair in vivo and is a promising candidate dressing for chronic refractory wound healing.