{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:15:33Z","timestamp":1785417333311,"version":"3.56.0"},"posted":{"date-parts":[[2025,11,4]]},"group-title":"Bioengineering","reference-count":53,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["HD083383"],"award-info":[{"award-number":["HD083383"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["TLTR001858"],"award-info":[{"award-number":["TLTR001858"]}],"id":[{"id":"https:\/\/ror.org\/04pw6fb54","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,11,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Surgical repair of pelvic organ prolapse (POP) is often augmented by polypropylene mesh to provide mechanical support to the vagina and improve anatomical outcomes as compared to native tissue repair. However, POP repair surgeries utilizing PPM have complications (most often pain or mesh exposure into the vagina) in over 10% of cases. Previous work has demonstrated that tensioning of meshes with certain geometries (diamond and hexagon pores), results in both planar (pore collapse) and nonplanar (wrinkles) deformations, significantly altering textile properties and impacting the host response. To further investigate the impact of mesh deformation on the host response, we implanted mesh in a validated non-human primate model via sacrocolpopexy with stable flat (square pores, N=20) versus deformed geometries (mesh loaded on the diamond prior to implantation resulting in collapsed pores and wrinkles, N=20). To investigate the impact of tension independent of deformation, we implanted on and off tension (10N, N=10 in each group). We hypothesized that more stable geometries trigger a healing response that achieves homeostasis while deformed mesh, by increasing the amount of material in contact with the host, triggers a maladaptive remodeling response with the formation of myofibroblasts. After twelve weeks, we found that mesh deformations and the absence of tension increase the amount of mesh per area on the vagina (mesh burden) and reproduced clinical complications (mesh exposure and vaginal thinning). Interestingly, MMT cells, or myofibroblasts co-expressing a macrophage marker (CD68), were seen to significantly increase in response to mesh burden, as well as respond hyper-locally to the mesh fiber interface. We observed decreased collagen density and more immature matrix deposited in conditions with higher MMT cell presence, showing more disorganization in deposited matrix with increased mesh burden, and the loss of tension. TGF-\u03b21, in both active and latent forms, increased with increasing mesh burden, and highest expression was observed in conditions precipitating the highest percentage of MMT cells, a possible mechanism of transdifferentiation. This study showed the importance of PPM mesh properties on mesh burden following tensioning, impact on MMT transdifferentiation, and the downstream effect of these changes on the host response and healing outcomes.<\/jats:p>","DOI":"10.1101\/2025.11.03.686251","type":"posted-content","created":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T21:05:25Z","timestamp":1762290325000},"source":"Crossref","is-referenced-by-count":0,"title":["Macrophage-to-Myofibroblast Transition (MMT) \u2013 an adverse response to polypropylene mesh implanted for pelvic organ prolapse repair surgery in a non-human primate model"],"prefix":"10.64898","author":[{"given":"Marrisa A.","family":"Therriault","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrina","family":"Knight","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srividya","family":"Kottapalli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Temitope","family":"Obisesan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malini","family":"Harinath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan N","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela A.","family":"Moalli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025110619001250000_2025.11.03.686251v1.1","doi-asserted-by":"publisher","DOI":"10.1067\/mob.2002.123819"},{"key":"2025110619001250000_2025.11.03.686251v1.2","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000000057"},{"key":"2025110619001250000_2025.11.03.686251v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0029-7844(97)00058-6"},{"key":"2025110619001250000_2025.11.03.686251v1.4","doi-asserted-by":"publisher","DOI":"10.1067\/mob.2003.101"},{"key":"2025110619001250000_2025.11.03.686251v1.5","first-page":"CD004014","article-title":"Surgery for women with anterior compartment prolapse","volume":"11","year":"2016","journal-title":"Cochrane Database Syst Rev"},{"issue":"11","key":"2025110619001250000_2025.11.03.686251v1.6","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1007\/s00192-011-1542-9","article-title":"Surgical management of pelvic organ prolapse in women: the updated summary version Cochrane review","volume":"22","year":"2011","journal-title":"Int Urogynecol J"},{"key":"2025110619001250000_2025.11.03.686251v1.7","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.ejogrb.2024.01.015","article-title":"Diagnosis and management of complications following pelvic organ prolapse surgery using a synthetic mesh: French national guidelines for clinical practice","volume":"294","year":"2024","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"2025110619001250000_2025.11.03.686251v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2012.02.034"},{"key":"2025110619001250000_2025.11.03.686251v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2017.07.006"},{"issue":"5","key":"2025110619001250000_2025.11.03.686251v1.10","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1097\/GCO.0000000000000313","article-title":"Exploring the basic science of prolapse meshes","volume":"28","year":"2016","journal-title":"Curr Opin Obstet Gynecol"},{"key":"2025110619001250000_2025.11.03.686251v1.11","first-page":"510","article-title":"Rethinking regenerative medicine: a macrophagecentered approach","volume":"5","year":"2014","journal-title":"Front Immunol"},{"key":"2025110619001250000_2025.11.03.686251v1.12","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.smim.2017.04.004","article-title":"Macrophage phenotype in response to ECM bioscaffolds","volume":"29","year":"2017","journal-title":"Semin Immunol"},{"issue":"4","key":"2025110619001250000_2025.11.03.686251v1.13","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1002\/jbm.b.33584","article-title":"Synthetic surgical meshes used in abdominal wall surgery: Part II-Biomechanical aspects","volume":"105","year":"2017","journal-title":"J Biomed Mater Res B Appl Biomater"},{"key":"2025110619001250000_2025.11.03.686251v1.14","unstructured":"Order to stop selling and distributing produces. 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