Dental Follicle-Derived Mesenchymal Stem Cell Exosome-Loaded Three-Dimensional Electrospun...

Diabetic foot ulcers are chronic wounds characterized by persistent inflammation and insufficient angiogenesis, leading to delayed healing and substantial clinical burden. This study presents a combined platform in which dental follicle-derived mesenchymal stem cell exosomes (DF-MSC-Exos) are integrated into three-dimensional (3D) electrospun poly-(ε-caprolactone)/gelatin (PCL/GEL) nanofiber scaffolds. The 3D scaffoldsfabricated using a custom collectorexhibited high porosity, rapid wettability, and water-vapor permeability conducive to cell infiltration and a moist wound environment. DF-MSC-Exos (200 μg per 2 × 5 mm scaffold) were loaded onto the nanofibers and evaluated in a streptozotocin-induced diabetic rat foot wound model. Compared with controls and blank scaffolds, exosome-loaded scaffolds accelerated wound closure (reaching 92.5 ± 2.4% by day 21 compared to 61.4 ± 4.0% for control), improved tissue organization, and reduced inflammatory infiltration by H&E analysis. Immunohistochemistry revealed a significant decrease in fibroblast growth factor in the NF + Exos group, a pattern consistent with enhanced early re-epithelialization and tempered late-phase fibroplasia; VEGF exhibited a modest pro-angiogenic increase. These histological and molecular readouts align with a pro-regenerative trajectorylower leukocytic burden, earlier epithelial coverage, and remodeling compatible with improved scar quality. In summary, DF-MSC-Exos delivered from a 3D PCL/GEL scaffold provide complementary structural guidance and sustained paracrine signaling, yielding faster and qualitatively superior healing in chronic diabetic wounds. This nanofiber-exosome platform is clinically relevant and scalable, and merits further mechanistic and translational evaluation.