LAUSR

BACKGROUND The use of polypropylene prolapse mesh to treat pelvic organ prolapse has been limited by mesh-related complications. Gynemesh PS mesh, implanted via sacrocolpopexy in rhesus macaques, negatively impacted vagina with thinning of vaginal muscularis and decreased vaginal smooth muscle contractility. The negative effect was attenuated when a bioscaffold derived from urinary bladder extracellular matrix (ECM) was used as a composite with Gynemesh PS. OBJECTIVE To further elucidate the impact of Gynemesh PS polypropylene mesh and MatriStem ECM bioscaffolds on the vaginal smooth muscle in terms of micro-morphology of vaginal smooth muscle (muscle bundles and individual myocytes), innervation and nerve-mediated contractile function following their implantations in a rhesus macaque model via sacrocolpopexy. STUDY DESIGN Thirty-two middle-aged rhesus macaques were randomized to undergo either a Sham surgery (Sham, n=8), or the implantation of Gynemesh PS alone (n=8), vs. composite mesh comprised of Gynemesh PS plus 2-ply MatriStem (n=8), vs. 6-ply MatriStem alone (n=8) via sacrocolpopexy. The graft-vagina complexes were harvested 3 months later. Histomorphometrics of smooth muscle bundles and myocytes were performed by immunofluorescent labeling of alpha smooth muscle actin (αSMA), caveolin-3 (membrane protein) and cell nuclei followed by confocal imaging. The cross-sectional diameters of smooth muscle bundles and individual myocytes were quantified using images randomly taken in at least five areas of each section of sample. Contractile proteins αSMA and smoothelin were quantified by Western immunoblotting. Nerve density was measured by immunohistochemical labeling of a pan-neuron marker, PGP9.5. Nerve-mediated smooth muscle contractility was quantified using electrical field stimulation. One-way ANOVA and appropriate post-hoc tests were used for statistical comparisons. RESULTS Compared to Sham, the implantation of Gynemesh PS alone resulted in a disorganized smooth muscle morphology with the number of small muscle bundles (cross-sectional diameter less than 20 μm) increased 67% (p=0.004) and the myocyte diameter decreased 22% (p<0.001). Levels of contractile proteins were all decreased vs. Sham with αSMA decreased by 68% (p=0.009), low molecular weight smoothelin by 51% (p=0.014), and high molecular weight smoothelin by 40% (p=0.015). Nerve density was decreased by 48% (p=0.03 vs. Sham) paralleled by a 63% decrease of nerve-mediated contractility (p=0.02). Following the implantation of composite mesh, the results of measurements were similar to Sham (all p>0.05) with a 39% increase in the myocyte diameter (p<0.001) and a 2-fold increase in the level of αSMA relative to Gynemesh (p=0.045). Following the implantation of MatriStem alone, the number of small muscle bundles were increased 54% vs. Sham (p=0.002) while the other parameters were not significantly different from Sham (all p>0.05). CONCLUSIONS The implantation of Gynemesh PS had a negative impact on the structural and functional integrity of vaginal smooth muscle evidenced by atrophic macro- and microscopic muscle morphology, decreased innervation and impaired contractile property, consistent with a maladaptive remodeling response. The ECM bioscaffold (MatriStem), when used with Gynemesh PS as a composite (2-ply), attenuated the negative impact of Gynemesh PS; when used alone (6-ply), induced adaptive remodeling as evidenced by an increased fraction of small smooth muscle bundles with normal contractility.