Vaginal degeneration following implantation of synthetic mesh with increased stiffness

Abstract

Objective: To compare the impact of the prototype prolapse mesh Gynemesh PS with that of two new-generation lower stiffness meshes, UltraPro and SmartMesh, on vaginal morphology and structural composition.

Design: A mechanistic study employing a nonhuman primate model.

Setting: Magee-Womens Research Institute at the University of Pittsburgh.

Population: Parous rhesus macaques, with similar age, weight, parity and Pelvic Organ Prolapse-Questionnaire scores.

Methods: Following Institutional Animal Care Use Committee approval, 50 rhesus macaques were implanted with Gynemesh PS (n = 12), UltraPro with its blue line perpendicular to the longitudinal axis of vagina (n = 10), UltraPro with its blue line parallel to the longitudinal axis of vagina (n = 8) or SmartMesh (n = 8) via sacrocolpopexy following hysterectomy. Sham-operated animals (n = 12) served as controls.

Main outcome measures: The mesh-vagina complex was removed after 12 weeks and analysed for histomorphology, in situ cell apoptosis, total collagen, elastin, glycosaminoglycan content and total collagenase activity. Appropriate statistics and correlation analyses were performed accordingly.

Results: Relative to sham and the two lower stiffness meshes, Gynemesh PS had the greatest negative impact on vaginal histomorphology and composition. Compared with sham, implantation with Gynemesh PS caused substantial thinning of the smooth muscle layer (1557 ± 499 μm versus 866 ± 210 μm, P = 0.02), increased apoptosis particularly in the area of the mesh fibres (P = 0.01), decreased collagen and elastin content (20%, P = 0.03 and 43%, P = 0.02, respectively) and increased total collagenase activity (135%, P = 0.01). Glycosaminoglycan, a marker of tissue injury, was highest with Gynemesh PS compared with sham and other meshes (P = 0.01).

Conclusion: Mesh implantation with the stiffer mesh Gynemesh PS induced a maladaptive remodelling response consistent with vaginal degeneration.

Figure 1

Abluminal view of the vaginal walls implanted with synthetic meshes demonstrating that mesh contour following implantation of of Gynemesh PS and UltraPro meshes is more apparent than Smartmesh which is highly integrated into the tissue.

Figure 2

Masson Trichrome staining of (A) sham; (B) Gynemesh PS; (C) UltraPro perpendicular; (D) UltraPro parallel; (E) SmartMesh. Arrows indicate mesh fibers. Compared to the sham group which had clearly delineated layers and organized smooth muscle fibers, the layers of the vagina were less clearly defined in the mesh implanted groups, particularly in the muscularis. Mesh insertion induced disruption of smooth muscle bundles and disorganization of the surrounding dense connective tissue. Magnification: 10 x.

Figure 3

Immunofluorescent labeling of smooth muscle and in situ cell apoptosis. The red signal represents positive staining of α-SMA; the green signal represents apoptotic cells; the blue signal represents nuclei. S indicates the smooth muscle layer. M indicates the area of mesh fibers. The thickness of smooth muscle layer was significantly reduced in the Gynmesh PS group. In addition, following implantation with Gynemesh PS, the number of apoptotic cells was significantly increased in the subepithelium and adventitia compared to sham and lower stiffness meshes, predominantly surrounding the mesh fibers. For the lower stiffness meshes, apoptotic cells were higher following implantation of UltraPro perpendicular and UltraPro parallel than Smartmesh. Magnification: x10.