Dental Follicle-Derived Mesenchymal Stem Cell Exosome-Loaded Three-Dimensional Electrospun Poly(ε-caprolactone)/Gelatin Scaffold Accelerates Diabetic Foot Wound Healing

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.