Vaginal degeneration following implantation of synthetic mesh with increased stiffness

Abstract

Objective To compare the impact of the prototype prolapse mesh Gynemesh PS to that of two new generation lower stiffness meshes, UltraPro and SmartMesh, on vaginal morphology and structural composition. Design A mechanistic study employing a non-human primate (NHP) model. Setting Magee-Womens Research Institute at the University of Pittsburgh. Population Parous rhesus macaques, with similar age, weight, parity and POP-Q scores. Methods Following IACUC 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) and SmartMesh (n=8) via sacrocolpopexy following hysterectomy. Sham operated animals (n=12) served as controls. Main Outcome Measures The mesh-vagina complex (MVC) was removed after 12 weeks and analyzed 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 to sham, implantation with Gynemesh PS caused substantial thinning of the smooth muscle layer (1557 ± 499μm vs 866 ± 210 μm, P=0.02), increased apoptosis particularly in the area of the mesh fibers (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)). GAG (glycosaminoglycan), a marker of tissue injury, was the highest with Gynemesh PS compared to sham and other meshes (P=0.01). Conclusion Mesh implantation with the stiffer mesh Gynemesh PS induced a maladaptive remodeling response consistent with vaginal degeneration.

Impact of Prolapse Meshes on the Metabolism of Vaginal Extracellular Matrix in Rhesus Macaque

“…Previously, we showed that mature elastin was decreased following implantation with Gynemesh PS and UltraPro, independent of the direction of implantation but did not change with Restorelle 6 . To determine whether elastin degradation was accounting for these results, we measured both tropoelastin degradation and mature elastin degradation ( Figure 4A).…”

“…Following implantation with Gynemesh PS by sacrocolpopexy, the quantity of collagen and elastin in the grafted vagina decreased by 20% and 43%, respectively, with impaired tissue function as measured in biomechanical tests 6,9 . Here, we demonstrate that the decreases in these key structural proteins is via accelerated degradation associated with an increase in active MMPs including the interstitial collagenases MMPs-1, -8, and -13 and the elastases MMPs-2, and -9.…”

Extracellular Matrix Regenerative Graft Attenuates the Negative Impact of Polypropylene Prolapse Mesh on Vagina in Rhesus Macaque

“…For histomorphometrics, biomechanical testing, collagen, and GAG content, previously published data on sham and Gynemeshimplanted vagina were used for comparison. 6,7 Ball-burst test for biomechanical properties…”

“…[1][2][3][4] Gynemesh PS (Ethicon, Sommersville, NJ), one of the most widely implanted polypropylene meshes, has been shown to induce a robust foreign-body response and degenerative changes in the vagina when implanted via sacrocolpopexy including a decrease in smooth muscle contractility and volume, a loss of mechanical integrity, a decrease in matrix structural proteins (collagen and elastin) accompanied by an increase in glycosaminoglycan (GAG) content, and an increase in the amount and activity of matrixdegrading proteases. [5][6][7][8] In theory, these negative effects could be overcome with the use of regenerative biomaterials either in combination with Gynemesh PS as a composite graft or alone with the elimination of permanent materials. However, given that the sacrocolpopexy is not an anatomical surgery and regenerative matrices are designed to restore or repair injured tissues in a sitespecific manner, it is not clear whether the use of a regenerative matrix in sacrocolpopexy surgery would be successful.…”

Temporal changes in the biomechanical properties of endometrial mesenchymal stem cell seeded scaffolds in a rat model

“…Ideally, these meshes should primarily support the damaged tissue, but also promote new tissue ingrowth and neovascularization, with limited fibrous capsule and scar tissue formation. It is desirable that this new connective tissue comprises collagen in sufficient quantities and organization to ensure the optimum biomechanical properties of strength and elasticity [8]. It has been reported that poor mechanical compliance between implanted mesh and tissue may lead to stress shielding [9] and potentially contribute to complications such as erosion into surrounding tissue [8,10] and dyspareunia [11].…”