Phytoextract-loaded bioinspired PLGA nanofibrous scaffold promotes diabetic wound healing via anti-inflammatory and antioxidant effects in in vitro and in vivo experimental models.

Diabetic wounds pose significant healing challenges due to persistent inflammation, oxidative stress, and impaired tissue regeneration. This study developed bioinspired PLGA-gelatin nanofibrous scaffolds encapsulating Vitex negundo (VN) and Jatropha multifida (JM) phytoextracts to mimic the extracellular matrix, enhance drug release, and promote wound healing via anti-inflammatory and antioxidant mechanisms in in vitro (HUVEC cells) and in vivo (streptozotocin-induced diabetic rat) models. VN-JM nanofibers exhibited uniform nanoscale morphology (255-280 nm) with successful phytoconstituent incorporation, while XRD analysis confirmed crystalline-to-amorphous transformation, indicating enhanced solubility. The nanofibers demonstrated high porosity (83.6 ± 0.9%), excellent swelling capacity (450 ± 18% at 24 h), and controlled biodegradation (63.5 ± 4.5% weight loss at 28 days), supporting their suitability as bioresorbable wound dressings. Furthermore, the formulation provided sustained drug release over 168 h, achieving approximately 90% cumulative release, thereby ensuring prolonged therapeutic availability at the wound site. At optimal doses, nanofibers enhanced HUVEC viability, reduced ROS (DCFH intensity, boosted colony formation, and enhances migration wound closure. In diabetic rats, daily topical application for 21 days yielded better wound closure at day 21, markedly lowered TNF-α, IL-6, and diminished lipid peroxidation, DCF, nitrite levels compared to gels and extracts. Histology showed complete re-epithelialization, fibroblast proliferation, neovascularization, and organized collagen in nanofiber-treated groups, outperforming diabetic controls and matching standard groups. These findings demonstrate VN+JM-loaded nanofibers could be taken as a promising regenerative scaffold for diabetic wounds by mitigating oxidative stress and inflammation.