Astragalus Polysaccharide Hydrogel Promotes Diabetic Wound Healing by Modulating Macrophage Polarization and the Immune Microenvironment

Diabetic foot ulcer (DFU) is a common complication of diabetes characterized by chronic inflammation, impaired tissue repair, and limited therapeutic options. Astragalus polysaccharide (APS) has immunomodulatory and pro-regenerative properties, but its therapeutic effects in diabetic wounds remain incompletely understood.

A diabetic full-thickness skin wound model was established in mice to evaluate the therapeutic efficacy of an APS-loaded hydrogel. Wound closure, COL-1 and α-SMA expression, macrophage phenotypes, and cytokine profiles were assessed. Macrophage depletion and adoptive transfer of APS-conditioned bone marrow-derived macrophages (BMDMs) were further performed to investigate the functional contribution of macrophages.

APS hydrogel significantly accelerated wound closure and increased COL-1 and α-SMA expression. Treatment increased F4/80⁺CD206⁺ macrophages while reducing F4/80⁺iNOS⁺ macrophages, accompanied by elevated IL-10 and IL-4 levels, whereas TNF-α and IL-6 remained largely unchanged. Macrophage depletion attenuated the wound-healing effects of APS hydrogel, whereas adoptive transfer of APS-conditioned BMDMs enhanced wound closure and tissue remodeling. No significant systemic toxicity was observed under the experimental conditions.

APS hydrogel promotes diabetic wound healing by reshaping the local immune microenvironment toward a reparative macrophage phenotype, thereby facilitating inflammation resolution and tissue repair.