A Dioscorea opposita Polysaccharide-Calcium Carbonate Microsphere-Doped Hydrogel for Accelerated Diabetic Wound Healing via Synergistic Glucose-Responsive Hypoglycemic and Anti-Inflammatory Effects

As common complications of diabetes, long-term hyperglycemia and inflammatory infiltration often lead to prolonged unhealing of chronic diabetic wounds. The natural hydrogel-containing plant polysaccharides were recorded to have effective hypoglycemic and anti-inflammatory effects. This study focused on the accelerating effect of diabetic wound healing of hydrogels doped with Dioscorea opposita polysaccharide (DOP)─calcium carbonate (CaCO 3 ) microspheres, which have glucose-responsive insulin release and anti-inflammatory effects. The hydrogel defined as PL–PVA/DOP-CaCO 3 was designed via the borate ester bonds between polylysine-phenylboronic acids (PL–PBA) and dihydroxyl groups of poly(vinyl alcohol) (PVA). DOP modified on the surface of CaCO 3 microspheres can simultaneously act with PBA to dope into the PL–PVA hydrogel and maintain glucose sensitivity. The mechanical and swelling properties of the hybrid hydrogels were reinforced by the incorporated microspheres. Meanwhile, the hyperglycemia was also regulated by the released insulin and DOP. The in vitro results indicated that the PL–PVA/DOP-CaCO 3 hydrogel had good biocompatibility and inflammatory activity and could promote fibroblast proliferation and migration. In vivo experiments demonstrated that the INS@PL–PVA/DOP-CaCO 3 hydrogel can significantly promote wound healing in diabetic rats by glucose-responsive regulation of hyperglycemia, inhibiting inflammation, improving angiogenesis, and accelerating the secretion of endothelial cells and proliferation of fibroblasts on wound tissues. The results bring new insights into the field of glucose-responsive hydrogels, showing their potential as drug delivery systems of macromolecular therapeutics to treat diabetic skin wounds.