Concentration-Optimized Astragalus Polysaccharide-Loaded PLCL Electrospun Dressings for the Treatment of Diabetic Wounds

This study aims to fabricate electrospun nanofiber membranes composed of poly(L-lactide-co-ε-caprolactone) (PLCL) incorporated with Astragalus polysaccharides (APS) (APS@PLCL), and to evaluate their efficacy in enhancing diabetic wound healing, as well as to determine the optimal concentration of drug loading.

APS was incorporated into the PLCL spinning solution through an HP-β-CD inclusion complexation approach to fabricate APS@PLCL membranes with theoretical drug loadings of 0%, 3%, 6%, and 9%. The membranes were characterized in terms of morphology, mechanical properties, drug loading capacity, and in vitro drug release profiles. Biocompatibility was assessed using the CCK-8 assay and live/dead staining. The wound healing efficacy was evaluated in a full-thickness skin defect model in diabetic mice (n = 6 per group, 24 mice in total). Collagen deposition, angiogenesis, and the expression of inflammatory factors were analyzed via histological staining, RT-qPCR, ELISA and Western blot.

All membranes demonstrated uniform morphology, encapsulation efficiencies exceeding 90%, favorable mechanical properties, and exhibited no cytotoxicity. APS@PLCL extract inhibits M1 polarization of RAW264.7 macrophages while promoting M2 polarization, as demonstrated by the reduced expression of iNOS and IL-1β and the elevated expression of Arg-1 and CD206. Compared to the 0% group, APS@PLCL significantly enhanced wound closure, with the 6% and 9% groups achieving the most pronounced effects, evidenced by a healing rate exceeding 90% at 14 days versus approximately 78% in the 0% group (p < 0.05). These groups also upregulated the expression of VEGF, CD31, α-SMA, and the anti-inflammatory cytokine IL-10, while downregulating pro-inflammatory markers TNF-α and IL-1β (p < 0.05), thereby facilitating organized collagen deposition. Meanwhile, APS@PLCL treatment is associated with decreased expression of TLR4 and reduced phosphorylation levels of p65, while total p65 levels remain unchanged, indicating that it inhibit the TLR4/NF-κB signaling pathway.

APS@PLCL effectively accelerates the healing of diabetic wounds by modulating inflammatory responses and promoting angiogenesis. Taking into account overall therapeutic efficacy and drug utilization, 6% APS@PLCL appears to be a more cost-effective candidate for further investigation. This finding offers a novel strategy for the treatment of diabetic wounds.