Yeast β-glucan accelerates diabetic wound healing via macrophage polarization and anti-inflammatory modulation

Diabetic foot ulcers (DFUs) represent a severe, non-healing complication of diabetes, primarily driven by chronic inflammation and impaired tissue regeneration. This study investigated the therapeutic efficacy and underlying immunological mechanisms of a novel topical formulation: a water-soluble β-glucan/cross-linked sodium hyaluronate hydrogel, on wound healing in db/db diabetic mice. Wound closure analysis demonstrated that daily application of the β-glucan hydrogel significantly accelerated healing, achieving an average closure rate of 90.95 %±3.15 % by postoperative day (POD) 14, markedly surpassing the 65.67 %±3.64 % observed in the control group. Histological examination revealed enhanced epithelialization, collagen deposition, and microvessel density (MVD), alongside a substantial reduction in total inflammatory cell and mast cell infiltration. Immunofluorescence and qRT-PCR analyses showed that β-glucan significantly promoted macrophage polarization toward the pro-reparative M2 phenotype (marked by increased CD206⁺ cells), downregulating pro-inflammatory factors (IL-1β, TNF-α) while simultaneously upregulating IL-10 and TGF-β. In conclusion, the β-glucan smearable hydrogel exhibits potent therapeutic capacity for diabetic wounds by resolving chronic inflammation and promoting tissue repair via the M2 macrophage polarization pathway. This finding offers a promising and non-invasive immunomodulatory strategy for DFU management.