Dynamic Hyaluronic Acid Hydrogels for Regulating Inflammation, Angiogenesis, and Metabolism to Heal Diabetic Wounds

The study introduces a novel dynamic hyaluronic acid (HA) hydrogel designed to address the challenges of healing diabetic foot ulcers and chronic wounds by regulating inflammation, angiogenesis, and metabolism. This hydrogel, which combines boronate and coordination chemistry, features injectability, self-healing, and diabetic wound-responsive degradation. It effectively transitions inflammation from the chronic to the proliferation and remodeling stages by promoting M1-to-M2 polarization and regulating inflammatory cytokines through reactive oxygen species elimination, H2S release, and Zn2+ regulation. The lead hydrogel, HTZS, enhances angiogenesis and metabolism, leading to neovascularization, re-epithelization, collagen-I deposition, and hair follicle regeneration, achieving complete healing and functional remodeling. This research highlights the potential of dynamic biopolymer hydrogels in advanced wound care.