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

Year: 2026
Type: article
Abstract: Purpose: 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. Methods: 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. Results: 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. Conclusion: 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.
Language: English
Subfield: Surgery
Field: Medicine
Open Access status: gold
Estimated APC paid: $2,836
OpenAlex ID: W7223318998
FWCI:
Cites: 34
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Related to: 10