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CAM-based implant to repair Stress Urinary Incontinence (SUI)

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:

Stress urinary incontinence (SUI) represents a significant medical burden, particularly among women, affecting [1] in [5] women[1,2]. SUI is characterized by involuntary leakage of urine during physical activities or during moments of exertion, such as sneezing or coughing[3]. It has a considerable social and economic impact on both society and individuals, and significantly reduces the quality of life[4-6] .

▷[1] Milsom, I. & Gyhagen, M. The prevalence of urinary incontinence. Climacteric 22, 217–222 (2019).

▷[2] Hampel, C. et al. Understanding the burden of stress urinary incontinence in Europe: A qualitative review of the literature. Eur Urol 46, 15–27 (2004).

▷[3] Haylen, B. T. et al. An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction. Int Urogynecol J 21, 5–26 (2010).

▷[4] Lose, G. The burden of stress urinary incontinence. European Urology, Supplements 4, 5–10 (2005).

▷[5] Victor W. Nitti, MD (Departmebt of Urology, New York University Shcool of Medecine, New York, N. The prevalence of urinary incontinence. Rev Urol (2001).

▷[6] Urology, T. E. A. of. Incontinence costs European society over 40 billion Euros per year. (23-2023).

▷[7] Bombieri, L. & Freeman, R. M. Surgery for stress urinary incontinence. Curr Obstet Gynaecol 13, 287–293 (2003).

▷[8] Glazener, C. M. A. What is the role of mid-urethral slings in the management of stress incontinence in women? Cochrane Database Syst Rev 7, ED000101 (2015).

▷[9] Lucas, M. G. et al. EAU guidelines on surgical treatment of urinary incontinence. Eur Urol 62, 1118–1129 (2012).

▷[10] Blanc, B., Agostini, A., Mulfinger, C., Crépin, M. G. & Pellerin, M. D. Surgical treatment of female stress urinary incontinence. Bull Acad Natl Med 189, 301–307 (2005).

▷[11] Klopfleisch, R. & Jung, F. The pathology of the foreign body reaction against biomaterials. J Biomed Mater Res A. doi: 10.1002/jbm.a.35958. (2017)

▷[12] 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).

▷[13] Medicines and Healthcare Products Regulatory Agency-MHRA. A summary of the evidence on the benefits and risks of vaginal mesh implants. 1–92 (2014).

▷[14] Wilkie, L. The Scottish Independent Review of the Use, Safety and Efficacy of Transvaginal Mesh Implants in the Treatment of Stress Urinary Incontinence and Pelvic Organ Prolapse in Women Final Report. The Scottish Government (8485-2017).

▷[15] Food & Drug Administration - FDA. FDA Public Health Notification: Serious Complications Associated with Transvaginal Placement of Surgical Mesh in Repair of Pelvic Organ Prolapse and Stress Urinary Incontinence. (20-2008).

▷[16] Han, J.-Y. Recurrent Urinary Tract Infection from Urethral Mesh Erosion after Midurethral Mesh Sling Surgery. Urogenital Tract Infection 14, 60 (2019).

▷[17] Tunn, R., Baessler, K., Knüpfer, S. & Hampel, C. Urinary Incontinence and Pelvic Organ Prolapse in Women. NICE guideline. doi:10.3238/arztebl.m2022.0406 (2019).

▷[18] 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).

▷[19] Ministry of health. Surgical mesh statement from Director-General of Health. Surgical mesh (23-2023).

▷[20] Medicines and Healthcare Products Regulatory Agency-MHRA. Pause on the use of vaginally inserted surgical mesh for stress urinary incontinence. News story 1 (17-2018).

▷[21] Magnan, L. et al. In vivo remodeling of human cell-assembled extracellular matrix yarns. Biomaterials 273, (2021).

▷[22] 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).

▷[23] 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).

▷[24] Wystrychowski, W. et al. First human use of an allogeneic tissue-engineered vascular graft for hemodialysis access. J Vasc Surg 60, 1353–1357 (2014).

▷[25] 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).

▷[26] 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).

▷[27] 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 SUI 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 [21-27]. This should result in tissue integration while avoiding chronic inflammation, pain, sling exposure, and infections, ultimately improving patients’ quality of life.

Supported by:

• European Research Council (ERC)

ERC Proof of Concept - Project POPTEX

The gold standard surgical treatment for SUI is the placement of a strong and hard synthetic mesh (polypropylene), known as a sling, beneath the urethra to support urethral closure during exertion[7-10]. The fundamental problems are that these plastics are extremely hard and are recognized as foreign bodies by the innate immune system of the patient[11]. This triggers a well-characterized “foreign body reaction”, resulting in a chronic inflammatory state and leading to many serious complications[12]. Typical complications are severe chronic pain, infection, and sling exposure (i.e., tissue perforation by the sling) through the urethra or the vaginal wall (Food & Drug Administration - FDA, 2008; Han, 2019; Medicines and Healthcare Products Regulatory Agency-MHRA, 2014., 2016; Wilkie, 2017)

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 [21-22].

Troubling reports of complications following implantation of urogenital slings for the treatment of SUI and Pelvic Organ Prolapse (POP) have prompted regulatory authorities to increase surveillance[17]. Since 2019, transvaginal meshes for POP treatment have been banned in most countries (France, the USA, Australia, etc.), and the use of slings for SUI treatment has already been suspended in several countries, such as the United Kingdom and New Zealand, raising concerns in the medical community about the future of this widely practiced procedure[18-20].

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