Polypropylene surgical mesh induces lipid oxidation in a nonhuman primate model

Abstract

Polypropylene mesh is widely used in surgery to support weak connective tissue, but pain and exposure complications limit vaginal implantation for pelvic organ prolapse. The increased complication rate with vaginal implantation is incompletely understood. We sought to compare the host response to low vs high polypropylene mesh burden after vaginal or abdominal implantation in rhesus macaques. We hypothesized that in both sites an increased mesh burden would result in increased malondialdehyde (MDA; a marker of lipid oxidative damage), heightened macrophage response, and increased apoptosis. Gynemesh PS and Restorelle implanted on the anterior abdominal wall were compared to a nonhuman primate sacrocolpopexy vaginal implantation model with Restorelle, which was intentionally and successively deformed to produce low, high, and highest mesh burden groups. Abdominal Gynemesh showed more CD68+ macrophages than lower mesh burden vaginal groups but not the highest burden group. In abdominal mesh, apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling assay was limited to areas immediately surrounding mesh, while in deformed vaginal mesh, increased apoptosis was seen in the subepithelium. Macrophages and apoptotic cells were correlated at both sites and MDA was correlated with abdominal macrophages and vaginal apoptotic indices. Regardless of implantation site, macrophages, apoptotic indices, and MDA levels were strongly correlated with mesh burden. These data indicate that mesh burden is a main driver in the abdominal and vaginal mesh innate immune response and suggest a possible pathway through which prolonged inflammation contributes to tissue damage in mesh complications, namely through the immune cell production of reactive oxygen species or through stress-shielding.

Statement of significance

When implanted on the vagina, polypropylene mesh is associated with a strong negative foreign body response that can result in mesh exposure into the vagina or other organs. The mechanistic pathway for mesh exposure is unknown. Here, we show that polypropylene mesh induced lipid oxidation, as measured by malondialdehyde, in both abdominal and vaginal mesh implants in a nonhuman primate model. Mesh burden was strongly correlated with macrophages, apoptotic indices, and MDA levels. Apoptosis in the subepithelium in deformed mesh samples may be a result of stress shielding or oxidative damage and may contribute to exposure complications. These data suggest a possible pathway through which prolonged inflammation surrounding a biomaterial implant results in tissue damage and implant exposure.