A glycopeptide-based pH-responsive hydrogel promotes diabetic wound healing via antimicrobial and remodeling microenvironment

Treating bacterium-infected diabetic wounds remains a major medical challenge. Antimicrobial activity, remodeling of oxidative stress-heavy and angiogenesis-impaired microenvironments are critical factors for effective wound healing. Hydrogels can function as drug delivery systems that encompass all these capabilities to enhance wound healing. In this study, we developed a glycopeptide-based hydrogel (DA/bF@OD-PL) composed of oxidized dextran (OD), polylysine (PL), dopamine (DA), and basic fibroblast growth factor (bF). This hydrogel exhibits excellent structural integrity, injectability, adhesion properties, swelling capacity, and degradability. Notably, the hydrogel is responsive to acidic conditions due to the presence of Schiff base bonds, enabling it to respond to the acidic environment characteristic of bacterium-infected wounds and release its encapsulated drugs accordingly. Among these components, PL has a strong antibacterial effect and can easily kill S. aureus and E. coli. DA effectively scavenges multiple reactive oxygen species (ROS) and induces macrophage polarization to M2 macrophages to alleviate oxidative stress. bF upregulates the expression of CD31 and vascular endothelial growth factor (VEGF) to promote angiogenesis. Finally, we validated the ability of this hydrogel to promote rapid wound healing in an S. aureus-infected diabetic mouse wound model.