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

Synthetic meshes are commonly used to repair pelvic organ prolapse. Increasing evidence of mesh-related complications, including mesh erosion and mesh exposure, led the Food and Drug Administration to issue warnings about use of synthetic mesh and to call for mechanistic studies. A recent study (by some of the same authors) that used a nonhuman primate sacrocolpopexy model showed that heavier-weight, lower-porosity, and higher-stiffness meshes result in thinner and biome-chanically inferior vaginas. The aim of this study was to define and compare alterations in collagen and elastin metabolism following the implantation of 3 synthetic meshes into the vagina of nonhuman primates with prolapse. The impact of the heavier, less porous, and stiffer prolapse mesh (Gynemesh PS) was compared with 2 lighter, more porous, and less-stiff meshes (UltraPro and Restorelle). Following hysterectomy, 39 middle-aged parous rhesus macaques were implanted via sacrocolpopexy with Gynemesh PS (n = 12), UltraPro with its blue line perpendicular to the longitudinal axis of vagina (low stiffness direction, n = 11), UltraPro with its blue line parallel to the longitudinal axis of vagina (high stiffness direction, n = 8), or Restorelle (n = 8). Sham-operated animals (n = 10) served as controls. The mesh-tissue complex was removed 12 weeks after surgery and analyzed. Relative to sham, Gynemesh PS increased degradation of both collagen and elastin, whereas UltraPro Perpendicular and UltraPro Parallel induced an increase only in elastin degradation. The mesh with the least impact was Restorelle. Compared with sham, increased degradation of collagen and elastin in vaginas implanted with Gynemesh PS was associated with a simultaneous increase in active matrix metalloproteinase 1 (MMP-1), MMP-8, MMP-13, and total MMP-2 and MMP-9 (all comparisons, P < 0.05). Increased degradation of elastin (tropoelastin and mature elastin) in the UltraPro-implanted vagina was associated with a concomitant increase of MMP-2 and MMP-9 (all comparisons, P < 0.05). Relative to sham, the ratio of collagen subtype III/I was higher in the Gynemesh PS and UltraPro perpendicular groups (both, P < 0.05). These data show that implantation of the heavier, less porous, and stiffer mesh, Gynemesh PS, degrades vaginal collagen and elastin, most likely as a result of increased MMP activity, and weakens the vaginal wall, predisposing to mesh exposure development.