Impact of polypropylene prolapse mesh on vaginal smooth muscle in rhesus macaque


      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, had a negative impact on the 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 was used as a composite with Gynemesh PS.


      The objective of the study was to further elucidate the impact of Gynemesh PS polypropylene mesh and MatriStem extracellular matrix bioscaffolds on the vaginal smooth muscle in terms of micromorphology 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, 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 5 areas of each section of sample. Contractile proteins alpha smooth muscle actin 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 analysis of variance and appropriate post hoc tests were used for statistical comparisons.


      Compared with 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 = .004) and the myocyte diameter decreased 22% (P < .001). Levels of contractile proteins were all decreased vs sham with alpha smooth muscle actin decreased by 68% (P = .009), low-molecular-weight smoothelin by 51% (P = .014), and high-molecular-weight smoothelin by 40% (P = .015). Nerve density was decreased by 48% (P = .03 vs sham) paralleled by a 63% decrease of nerve-mediated contractility (P = .02). Following the implantation of composite mesh, the results of measurements were similar to sham (all P > .05), with a 39% increase in the myocyte diameter (P < .001) and a 2-fold increase in the level of alpha smooth muscle actin relative to Gynemesh (P = .045). Following the implantation of MatriStem alone, the number of small muscle bundles were increased 54% vs sham (P = .002), while the other parameters were not significantly different from sham (all P > .05).


      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 extracellular matrix bioscaffold (MatriStem), when used with Gynemesh PS as a composite (2 ply), attenuated the negative impact of Gynemesh PS; when used alone (6 ply), it induced adaptive remodeling as evidenced by an increased fraction of small smooth muscle bundles with normal contractility.

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        • Maclennan A.H.
        • Taylor A.W.
        • Wilson D.H.
        • Wilson D.
        The prevalence of pelvic floor disorders and their relationship to gender, age, parity and mode of delivery.
        BJOG. 2000; 107: 1460-1470
        • Nygaard I.
        • Barber M.D.
        • Burgio K.L.
        • et al.
        Prevalence of symptomatic pelvic floor disorders in US women.
        JAMA. 2008; 300: 1311-1316
        • Samuelsson E.C.
        • Victor F.T.
        • Tibblin G.
        • Svardsudd K.F.
        Signs of genital prolapse in a Swedish population of women 20 to 59 years of age and possible related factors.
        Am J Obstet Gynecol. 1999; 180: 299-305
        • Luber K.M.
        • Boero S.
        • Choe J.Y.
        The demographics of pelvic floor disorders: current observations and future projections.
        Am J Obstet Gynecol. 2001; 184 (discussion 1501-3): 1496-1501
        • Wu J.M.
        • Hundley A.F.
        • Fulton R.G.
        • Myers E.R.
        Forecasting the prevalence of pelvic floor disorders in US women: 2010 to 2050.
        Obstet Gynecol. 2009; 114: 1278-1283
        • Wu J.M.
        • Kawasaki A.
        • Hundley A.F.
        • Dieter A.A.
        • Myers E.R.
        • Sung V.W.
        Predicting the number of women who will undergo incontinence and prolapse surgery, 2010 to 2050.
        Am J Obstet Gynecol. 2011; 205: 230.e1-230.e5
        • Siff L.N.
        • Barber M.D.
        Native tissue prolapse repairs: comparative effectiveness trials.
        Obstet Gynecol Clin North Am. 2016; 43: 69-81
        • Olsen A.L.
        • Smith V.J.
        • Bergstrom J.O.
        • Colling J.C.
        • Clark A.L.
        Epidemiology of surgically managed pelvic organ prolapse and urinary incontinence.
        Obstet Gynecol. 1997; 89: 501-506
        • Jelovsek J.E.
        • Barber M.D.
        • Brubaker L.
        • et al.
        Effect of uterosacral ligament suspension vs sacrospinous ligament fixation with or without perioperative behavioral therapy for pelvic organ vaginal prolapse on surgical outcomes and prolapse symptoms at 5 years in the OPTIMAL randomized clinical trial.
        JAMA. 2018; 319: 1554-1565
        • Maher C.
        • Feiner B.
        • Baessler K.
        • Schmid C.
        Surgical management of pelvic organ prolapse in women.
        Cochrane Database Syst Rev. 2013; : CD004014
        • Milani R.
        • Salvatore S.
        • Soligo M.
        • Pifarotti P.
        • Meschia M.
        • Cortese M.
        Functional and anatomical outcome of anterior and posterior vaginal prolapse repair with prolene mesh.
        BJOG. 2005; 112: 107-111
        • Lamblin G.
        • Van-Nieuwenhuyse A.
        • Chabert P.
        • Lebail-Carval K.
        • Moret S.
        • Mellier G.
        A randomized controlled trial comparing anatomical and functional outcome between vaginal colposuspension and transvaginal mesh.
        Int Urogynecol J. 2014; 25: 961-970
        • Liang R.
        • Abramowitch S.
        • Knight K.
        • et al.
        Vaginal degeneration following implantation of synthetic mesh with increased stiffness.
        BJOG. 2013; 120: 233-243
        • Feola A.
        • Abramowitch S.
        • Jallah Z.
        • et al.
        Deterioration in biomechanical properties of the vagina following implantation of a high-stiffness prolapse mesh.
        BJOG. 2013; 120: 224-232
        • Feola A.
        • Barone W.
        • Moalli P.
        • Abramowitch S.
        Characterizing the ex vivo textile and structural properties of synthetic prolapse mesh products.
        Int Urogynecol J. 2013; 24: 559-564
        • Shepherd J.P.
        • Feola A.J.
        • Abramowitch S.D.
        • Moalli P.A.
        Uniaxial biomechanical properties of seven different vaginally implanted meshes for pelvic organ prolapse.
        Int Urogynecol J. 2012; 23: 613-620
        • Gamble J.G.
        • Edwards C.C.
        • Max S.R.
        Enzymatic adaptation in ligaments during immobilization.
        Am J Sports Med. 1984; 12: 221-228
        • Majima T.
        • Yasuda K.
        • Tsuchida T.
        • et al.
        Stress shielding of patellar tendon: effect on small-diameter collagen fibrils in a rabbit model.
        J Orthop Sci. 2003; 8: 836-841
        • Woo S.L.
        • Gomez M.A.
        • Woo Y.K.
        • Akeson W.H.
        Mechanical properties of tendons and ligaments. II. The relationships of immobilization and exercise on tissue remodeling.
        Biorheology. 1982; 19: 397-408
        • Yamamoto N.
        • Ohno K.
        • Hayashi K.
        • Kuriyama H.
        • Yasuda K.
        • Kaneda K.
        Effects of stress shielding on the mechanical properties of rabbit patellar tendon.
        J Biomech Eng. 1993; 115: 23-28
        • Badylak S.F.
        • Freytes D.O.
        • Gilbert T.W.
        Reprint of: Extracellular matrix as a biological scaffold material: Structure and function.
        Acta Biomater. 2015; 23: S17-S26
        • Brown B.N.
        • Ratner B.D.
        • Goodman S.B.
        • Amar S.
        • Badylak S.F.
        Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine.
        Biomaterials. 2012; 33: 3792-3802
        • Nagatomi J.
        • Toosi K.K.
        • Grashow J.S.
        • Chancellor M.B.
        • Sacks M.S.
        Quantification of bladder smooth muscle orientation in normal and spinal cord injured rats.
        Ann Biomed Eng. 2005; 33: 1078-1089
        • Liang R.
        • Knight K.
        • Barone W.
        • et al.
        Extracellular matrix regenerative graft attenuates the negative impact of polypropylene prolapse mesh on vagina in rhesus macaque.
        Am J Obstet Gynecol. 2017; 216: 153.e1-153.e9
        • Lowalekar S.K.
        • Cristofaro V.
        • Radisavljevic Z.M.
        • Yalla S.V.
        • Sullivan M.P.
        Loss of bladder smooth muscle caveolae in the aging bladder.
        Neurourol Urodyn. 2012; 31: 586-592
        • Song K.S.
        • Scherer P.E.
        • Tang Z.
        • et al.
        Expression of caveolin-3 in skeletal, cardiac, and smooth muscle cells. Caveolin-3 is a component of the sarcolemma and co-fractionates with dystrophin and dystrophin-associated glycoproteins.
        J Biol Chem. 1996; 271: 15160-15165
        • Liang R.
        • Zong W.
        • Palcsey S.
        • Abramowitch S.
        • Moalli P.A.
        Impact of prolapse meshes on the metabolism of vaginal extracellular matrix in rhesus macaque.
        Am J Obstet Gynecol. 2015; 212: 174.e1-174.e7
        • Skoczylas L.C.
        • Jallah Z.
        • Sugino Y.
        • et al.
        Regional differences in rat vaginal smooth muscle contractility and morphology.
        Reprod Sci. 2013; 20: 382-390
        • Jallah Z.
        • Liang R.
        • Feola A.
        • et al.
        The impact of prolapse mesh on vaginal smooth muscle structure and function.
        BJOG. 2016; 123: 1076-1085
        • Kramer J.
        • Quensel C.
        • Meding J.
        • Cardoso M.C.
        • Leonhardt H.
        Identification and characterization of novel smoothelin isoforms in vascular smooth muscle.
        J Vasc Res. 2001; 38: 120-132
        • Barone W.R.
        • Moalli P.A.
        • Abramowitch S.D.
        Textile properties of synthetic prolapse mesh in response to uniaxial loading.
        Am J Obstet Gynecol. 2016; 215: 326.e1-326.e9
        • Otto J.
        • Kaldenhoff E.
        • Kirschner-Hermanns R.
        • Muhl T.
        • Klinge U.
        Elongation of textile pelvic floor implants under load is related to complete loss of effective porosity, thereby favoring incorporation in scar plates.
        J Biomed Mater Res A. 2014; 102: 1079-1084
        • Bono N.
        • Pezzoli D.
        • Levesque L.
        • et al.
        Unraveling the role of mechanical stimulation on smooth muscle cells: a comparative study between 2D and 3D models.
        Biotechnol Bioeng. 2016; 113: 2254-2263
        • Shkumatov A.
        • Thompson M.
        • Choi K.M.
        • et al.
        Matrix stiffness-modulated proliferation and secretory function of the airway smooth muscle cells.
        Am J Physiol Lung Cell Mol Physiol. 2015; 308: L1125-L1135
        • Grootaert M.O.J.
        • Moulis M.
        • Roth L.
        • et al.
        Vascular smooth muscle cell death, autophagy and senescence in atherosclerosis.
        Cardiovasc Res. 2018; 114: 622-634
        • Shea-Donohue T.
        • Notari L.
        • Sun R.
        • Zhao A.
        Mechanisms of smooth muscle responses to inflammation.
        Neurogastroenterol Motil. 2012; 24: 802-811
        • Geng Y.J.
        • Wu Q.
        • Muszynski M.
        • Hansson G.K.
        • Libby P.
        Apoptosis of vascular smooth muscle cells induced by in vitro stimulation with interferon-gamma, tumor necrosis factor-alpha, and interleukin-1 beta.
        Arterioscler Thromb Vasc Biol. 1996; 16: 19-27
        • Boreham M.K.
        • Wai C.Y.
        • Miller R.T.
        • Schaffer J.I.
        • Word R.A.
        Morphometric analysis of smooth muscle in the anterior vaginal wall of women with pelvic organ prolapse.
        Am J Obstet Gynecol. 2002; 187: 56-63
        • Boreham M.K.
        • Wai C.Y.
        • Miller R.T.
        • Schaffer J.I.
        • Word R.A.
        Morphometric properties of the posterior vaginal wall in women with pelvic organ prolapse.
        Am J Obstet Gynecol. 2002; 187 (discussion 1508-9): 1501-1508
        • Northington G.M.
        • Basha M.
        • Arya L.A.
        • Wein A.J.
        • Chacko S.
        Contractile response of human anterior vaginal muscularis in women with and without pelvic organ prolapse.
        Reprod Sci. 2011; 18: 296-303
        • Liang R.
        • Fawcett M.
        • Shaffer R.
        • Palcsey S.
        • Moalli P.
        Impact of aging on vaginal smooth muscle: a morphometric study.
        Female Pelvic Med Reconstr Surg. 2014; 20: S128
        • Badylak S.F.
        • Gilbert T.W.
        Immune response to biologic scaffold materials.
        Semin Immunol. 2008; 20: 109-116
        • Brown B.N.
        • Londono R.
        • Tottey S.
        • et al.
        Macrophage phenotype as a predictor of constructive remodeling following the implantation of biologically derived surgical mesh materials.
        Acta Biomater. 2012; 8: 978-987