OBJECTIVES: The purpose of this study was to explore the utility of an injectable purified exosome product derived from human apheresis blood to (1) augment surgical closure of vaginal mesh exposures, and (2) serve as a stand-alone therapy for vaginal mesh exposure. METHODS: Sixteen polypropylene meshes (1×1-3×3 cm) were implanted in the vaginas of 7 Yorkshire-crossed pigs by urogynecologic surgeons (day 0). On day 7, group 1 underwent surgical intervention via vaginal tissue suture reclosure with (n=2 pigs, n=4 meshes) or without (n=2 pigs, n=4 meshes) exosome injection; group 2 underwent medical intervention with an exosome injection (n=3, n=8 meshes). One animal in group 2 was given oral 2'-deoxy-5-ethynyluridine to track cellular regeneration. Euthansia occurred at 5 weeks. RESULTS: Mesh exposures treated with surgical closure alone experienced reexposure of the mesh. Exosome treatment with or without surgical closure resulted in partial to full mesh exposure resolution up to 3×3 cm. Exosome-treated tissues had significantly thicker regenerated epithelial tissue (208 μm exosomes-only and 217 μm surgery+exosomes, versus 80 μm for surgery-only; P < 0.05); evaluation of 2'-deoxy-5-ethynyluridine confirmed de novo regeneration throughout the epithelium and underlying tissues. Capillary density was significantly higher in the surgery+exosomes group (P = 0.03). Surgery-only tissues had a higher inflammatory and fibrosis response as compared with exosome-treated tissues. CONCLUSIONS: In this pilot study, exosome treatment augmented healing in the setting of vaginal mesh exposure, reducing the incidence of mesh reexposure after suture closure and decreasing the area of mesh exposure through de novo tissue regeneration after exosome injection only. Further study of varied local tissue conditions and mesh configurations is warranted.