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CAM-based implant to repair Pelvic Organ Prolapse (POP)

Dr. Nicolas L'Heureux

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Contact

Linkedin biotis-bordeaux

Secretary Email

33 (0)5 57 57 14 88

Bioingénierie Tissulaire (BioTis)

Physical Address:

Batiment BBS (Bordeaux Biologie Santé), 5e étage

2, rue du Dr Hoffmann Martinot,

33000, Bordeaux, France

Mailing Address:

Université de Bordeaux, Campus Carreire

146, rue Léo Saignat, Case 84,

33076, Bordeaux Cedex, France

Abstract

Reference

Dr. Diane Potart

Project Leader

The problem:

Pelvic Organ Prolapse (POP) is a major medical issue for women, with [1] in [10] undergoing POP surgery at some point in her lifetime [1]. POP is the descent of one or more pelvic organs (bladder, uterus, or rectum) into the vagina, resulting in vaginal bulging or protrusion. It is a cause of urinary, bowel, and sexual dysfunction, abdominopelvic pain, and psychosocial distress, leading to a very significant reduction in quality of life [2,3] .

▷[1] Brown, H. W. et al. International urogynecology consultation chapter 1 committee 2: Epidemiology of pelvic organ prolapse: prevalence, incidence, natural history, and service needs. Int Urogynecol J 33, 173–187 (2022).

▷[2] Harvey, M.-A. et al. International Urogynecology Consultation Chapter 1 Committee 5: relationship of pelvic organ prolapse to associated pelvic floor dysfunction symptoms: lower urinary tract, bowel, sexual dysfunction and abdominopelvic pain. Int Urogynecol J 32, 2575–2594 (2021).

▷[3] Robinson, D. et al. International Urogynaecology Consultation chapter 1 committee 4: patients’ perception of disease burden of pelvic organ prolapse. Int Urogynecol J 33, 189–210 (2022).

▷[4] American Urogynecologic Society & International Urogynecological Association. Joint Report on Terminology for Surgical Procedures to Treat Pelvic Organ Prolapse. Female Pelvic Med Reconstr Surg 26, 173–201 (2020).

▷[5] Mangir, N., Aldemir Dikici, B., Chapple, C. R. & MacNeil, S. Landmarks in vaginal mesh development: polypropylene mesh for treatment of SUI and POP. Nat Rev Urol 16, 675–689 (2019).

▷[6] Klopfleisch, R. & Jung, F. The pathology of the foreign body reaction against biomaterials. J Biomed Mater Res A https://doi.org/10.1002/jbm.a.35958 (2017) doi:10.1002/jbm.a.35958.

▷[7] Nolfi, A. L. et al. Host response to synthetic mesh in women with mesh complications. Am J Obstet Gynecol 215, 206.e1-206.e8 (2016).

▷[8] Nygaard, I. et al. Long-term outcomes following abdominal sacrocolpopexy for pelvic organ prolapse. Urology 309, 2016–2024 (2013).

▷[9] Fritel, X. et al. Complications after pelvic floor repair surgery (with and without mesh): short-term incidence after 1873 inclusions in the French VIGI-MESH registry. BJOG 127, 88–97 (2020).

▷[10] Diwadkar, G. B., Barber, M. D., Feiner, B., Maher, C. & Jelovsek, E. J. Complication and Reoperation Rates After Apical Vaginal Prolapse Surgical Repair. Obstet Gynecol 113, 367–373 (2009).

▷[11] Abbott, S. et al. Evaluation and management of complications from synthetic mesh after pelvic reconstructive surgery: A multicenter study. Am J Obstet Gynecol 210, 163.e1-163.e8 (2014).

▷[12] Mairesse, S., Chazard, E., Giraudet, G., Cosson, M. & Bartolo, S. Complications and reoperation after pelvic organ prolapse, impact of hysterectomy, surgical approach and surgeon experience. Int Urogynecol J 31, 1755–1761 (2020).

▷[13] Zambon, J. P. & Badlani, G. H. Vaginal Mesh Exposure Presentation, Evaluation, and Management. Curr Urol Rep 17, 1–8 (2016).

▷[14] U.S. Food & Drug Administration. FDA takes action to protect women’s health, orders manufacturers of surgical mesh intended for transvaginal repair of pelvic organ prolapse to stop selling all devices. Press Announcements 1.

▷[15] Ng-Stollmann, N., Fünfgeld, C., Gabriel, B. & Niesel, A. The international discussion and the new regulations concerning transvaginal mesh implants in pelvic organ prolapse surgery. Int Urogynecol J 31, 1997–2002 (2020).

▷[16] Dyer, O. Johnson and Johnson faces lawsuit over vaginal mesh devices. BMJ 353, i3045 (2016).

▷[17] Llamas, M. Transvaginal Mesh Lawsuits. drugwatch 1.

▷[18] Magnan, L. et al. In vivo remodeling of human cell-assembled extracellular matrix yarns. Biomaterials 273, (2021).

▷[19] Potart, D. et al. The Cell-Assembled extracellular Matrix: a focus on the storage stability and terminal sterilization of this human ‘bio’ material. Acta Biomater 166, 133–146 (2023).

▷[20] Torres, Y. et al. Production and characterization of threads and textiles made from cell-assembled extracellular matrix: Translation from human to ovine cells to support allogeneic studies. Acta Biomater 202, 152–169 (2025).

▷[21] Wystrychowski, W. et al. First human use of an allogeneic tissue-engineered vascular graft for hemodialysis access. J Vasc Surg 60, 1353–1357 (2014).

▷[22] Konig, G. et al. Mechanical properties of completely autologous human tissue engineered blood vessels compared to human saphenous vein and mammary artery. Biomaterials 30, 1542–1550 (2009).

▷[23] L’Heureux, N., McAllister, T. N. & De La Fuente, L. M. Tissue-engineered blood vessel for adult arterial revascularization. The New England Journal of Medecine 357, 1451–1453 (2007).

▷[24] McAllister, T. N. et al. Effectiveness of haemodialysis access with an autologous tissue-engineered vascular graft: a multicentre cohort study. The Lancet 373, 1440–1446 (2009).

Dr. Yoann Torres

Collaborator

A CAM-based implant for POP repair represents a new paradigm. Rather than “fighting the body” by implanting an indestructible, ultra-strong, and hard material, we provide a matrix with physiological mechanical properties that can be remodeled by the host. Based on extensive human and animal data, we believe that the CAM will be recolonized by host cells and undergo very slow, physiological turnover [18-24]. This should result in tissue integration while avoiding chronic inflammation, pain, mesh exposure, and infections, ultimately improving patients’ quality of life.

Supported by:

• European Research Council (ERC)

ERC Proof of Concept - Project POPTEX

• Agence Nationale de la Recherche (ANR)

ANR PRCE - Project BIOTEX4POP

• Région Nouvelle-Aquitaine

Recherche en Nouvelle-Aquitaine - Project BIOTEX4POP

• Banque Publique d’Investissement

iPhD award – Project CAMATISS

• University of Bordeaux

UBooster award – Project CAMATISS

During POP surgery, the prolapsed organs are lifted back into their normal position and held in place by attachment to nearby support structures [4]. Most common procedures use a strong and hard synthetic mesh (polypropylene) to provide durable support [5] .

The fundamental problems are that these plastics are extremely hard and are recognized as foreign bodies by the innate immune system of the patient [6]. This triggers a well-characterized “foreign body reaction”, resulting in a chronic inflammatory state and leading to many serious complications [7]. Common complications include severe chronic pain, infection, and mesh exposure (i.e., tissue perforation by the mesh), which lead to perforation of the bladder, vagina, or rectum wall[8-13].

In 2019, overwhelming evidence of frequent complications led the FDA to order manufacturers of surgical mesh intended for transvaginal repair of POP to stop selling those devices [14]. The use of transvaginal POP meshes is now prohibited in France and other countries such as the USA and Australia [15]. Moreover, the emergence of these high rates of complications has led to major scandals and multimillion-dollar lawsuits worldwide [16,17].

Therefore, there is an urgent clinical need for new and innovative solutions.

The solution:

We propose a new solution based on Cell-Assembled extracellular Matrix (CAM), a unique biomaterial produced in vitro by normal adult human fibroblasts. This completely biological, non-living, and human material is robust without the need for chemical crosslinking or synthetic scaffolding. Importantly, because its ultrastructure is created by cells, it is not recognized as foreign by the innate immune system when implanted in vivo [18,19].