Impact of prolapse meshes on the metabolism of vaginal extracellular matrix in rhesus macaque

Abstract

Objective The impact of polypropylene mesh implantation on vaginal collagen and elastin metabolism was analyzed using a nonhuman primate model to further delineate the mechanism of mesh induced complications. Methods 49 middle aged parous rhesus macaques underwent surgical implantation of 3 synthetic meshes via sacrocolpopexy. Gynemesh PS (n=12) and two lower weight, higher porosity, lower stiffness meshes - UltraPro (n = 19) and Restorelle (n=8) were implanted, in which UltraPro was implanted with its blue orientation lines perpendicular (low stiffness direction, n=11) and parallel (high stiffness direction, n=8) to the longitudinal axis of vagina. Sham operated animals were used as controls (n=10). Twelve weeks after surgery, the meshtissue complex was excised and analyzed. Results Relative to Sham, Gynemesh PS had a negative impact on the metabolism of both collagen and elastin favoring catabolic reactions while UltraPro only induced an increase in elastin degradation. Restorelle had the least impact. As compared to Sham, the degradation of collagen and elastin in the vagina implanted with Gynemesh PS was increased with a simultaneous increase in active MMP-1, -8, -13 and total MMP-2, -9 (all P<0.05). The degradation of elastin (tropoelastin and mature elastin) was increased in the UltraPro implanted vagina with a concomitant increase of MMP-2, and -9 (all P<0.05). Collagen subtype ratio III/I was increased in both Gynemesh PS and UltraPro perpendicular groups (P<0.05). Conclusion Following implantation with the heavier, less porous and stiffer mesh, Gynemesh PS, the degradation of vaginal collagen and elastin exceeded synthesis, most likely as a result of increased activity of MMPs, resulting in a structurally compromised tissue.

Host response to synthetic mesh in women with mesh complications

“…20 Additional pieces of vagina-mesh-complexes and nonmesh control tissue were embedded into O.C.T. compound (Tissue-Tek; Sakura Finetek USA Inc, Torrance, CA), flash frozen in liquid nitrogen, sectioned (7 µm), and stored at −80°C.…”

“…26,27 In a nonhuman primate model, Gynemesh PS caused a decrease in key structural proteins (collagen and elastin) and increased MMP activity that led to thinning of the underlying and associated tissues and a deterioration of mechanical properties. 20,28,29 Gynemesh PS has a highly unstable geometry when loaded that resulted in pore collapse and increasing stiffness of the product. 30,31 Because virtually all meshes that are removed from women with complications have evidence of deformation and pore collapse, 32–36 mesh exposure may represent a mechanical phenomenon in which altered mesh geometries result in increased mesh stiffness, which, in turn, leads to a degenerative response as a result of stress shielding and ongoing destructive inflammation.…”

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

“…Ratios of collagen subtype III/I in the tissue of GVC were determined as previously described 8,26 and calculated as a1(III) ×2/α1(I) ×3 normalized by the ratio of purified collagen I/III.…”

“…[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.…”

Exploring the basic science of prolapse meshes

“…The tissue incorporation into the mesh was poor with increased cell apoptosis; particularly in the area of mesh fibers. Increased collagen and elastin degradation were accompanied by an increase in active matrix metalloproteinase (MMP)-1, -8, -13, and total MMP-2 and -9 indicative of ongoing tissue destruction [30 ▪ ]. While these degenerative changes could be attributed to ‘stress shielding’ as Gynemesh is one of the stiffest prolapse meshes, it is not clear whether the response is purely mechanical or the host is simply responding to an increased mesh burden since mesh stiffness is directly related to mesh weight and porosity.…”