Project 444042

Urologic and gynecologic patients often have problems requiring surgical reconstruction to recreate a normal function, notably for vaginal reconstruction and for the correction of stress urinary incontinence (SUI). Vaginal reconstruction is still a challenge due to the limited availability of suitable tissue for vaginal replacement. Traditional intervention methods have varying degrees of morbidity. More than 200 million people worldwide, 30-40% of all women during their lifetime, suffer from SUI. Synthetic midurethral slings (MUS) are the gold standard treatment for female patients with SUI. They have excellent short-term cure rates even if their efficacy tends to decrease over time. Nevertheless, campaigns against synthetic MUS led to their abolishment in many countries including severe restrictions in Canada. The traditional autologous fascial sling MUS, has then reemerged as a viable alternative. But, the readoption of autologous MUS is slow due to the surgical technical challenge and perceived higher morbidity rates. Interestingly, tissue engineering (TE) aims to replace dysfunctional tissues and organs. We successfully assembled a TE vaginal model (VM) using the patients' own cells. It has great histological organization and excellent mechanical resistance; hence, it would be possible to use it as a VM for reconstruction, or to serve as a MUS to correct SUI. We propose to reconstruct a vaginal substitute using patient's cells: autologous and free of synthetic material. We will also engineer a MUS made only with fibroblasts, to replace the synthetic material causing the actual turmoil. The development of autologous VM and MUS reconstructed by TE would significantly advance urology/gynecology and would have a considerable clinical impact. The expertise gathered in this research program in TE with Drs Bolduc, Germain, Ruel, and collaborators: Drs Bureau and Nadeau, combine strong clinical and basic science skills and gives excellent assurance of success.