Best Basic Science Paper: Exosomes for Prevention of Mesh Complications in a Porcine Sacrocolpopexy Model

Objectives: Surgical implantation of polypropylene mesh during sacrocolpopexy is an accepted and durable treatment for women experiencing pelvic organ prolapse, but carries a risk of vaginal mesh exposure, which is often treated via mesh excision. In our pilot studies using a porcine model, exosome injections (purified exosome product; PEP) induced tissue regeneration and resolved vaginal mesh exposures. In this study we aimed to evaluate the efficacy of PEP for prevention of vaginal mesh exposure in high-risk mesh configurations and examine changes to the local tissue.

Methods: 10 Yorkshire-crossed pigs (6 PEP, 4 control) underwent a hysterectomy, oophorectomy, and mesh sacrocolpopexy. Mesh was implanted in two high-risk configurations per animal – a mesh fold ventrally and a vaginotomy dorsally. 20% PEP mixed with hyaluronic acid (HA) or HA-only (control) was injected at the time of surgery. At 12 weeks postoperatively, animals were euthanized and evaluated for presence of mesh exposure. Hematoxylin and Eosin staining, Masson’s trichrome staining, and Tunel assay were performed to examine changes to the adjacent tissues. Inflamation, fibrosis, neovascularization, and necrosis were scored using a severity index (score 0-4), by a blinded Pathologist. Non-parametric statistical tests were performed.

Results: Only the control animals experienced mesh exposure (Fig 1A): 2 of the tissues with baseline vaginotomy and 4 of the tissues with the mesh fold. None of the PEP-treated tissues, vaginotomy nor mesh fold, demonstrated mesh exposure (Fig 1B). Histologic evaluation (Fig 1C-F) demonstrated lower scores for fibrosis in the PEP-treated tissues (p < 0.05) relative to controls. Median scores for inflammation and neovascularization were not statistically different. Control tissues with the mesh fold had higher Tunel positive area (i.e. more necrosis; median(IQR): 18.9(5.50, 25.6) vs 0.40(0.01, 3.11); p=0.02).

Conclusions: Exosome injection at the time of high-risk mesh implantation decreased the incidence of vaginal mesh exposures 12 weeks postoperatively. Mesh exposures are more common following implantation of mesh in a folded configuration than with a vaginotomy; exposure risk is mitigated by PEP treatment, which results in decreased tissue fibrosis and necrosis. Sustained mesh exposure prevention should be evaluated.

Figure 1: A-B. Gross evaluation of explanted mesh/vaginal tissue complexes in control (A) and PEP-treated (B) animals; the location of the vaginotomy is marked with stippled diamonds; the folded mesh area is marked by solid-line rectangles. C-F: Masson’s Trichrome staining of control (C,E) and PEP-treated (D,F) tissues across the two high-risk mesh configurations.