Novel injectable urethral bulking agents for the treatment of urinary incontinence

Stress urinary incontinence is a highly prevalent disorder resulting from weak urethral closure mechanisms. Endoscopic injection of a urethral bulking agent (UBA) under the urethral mucosa increases coaptation, which improves continence. Collagen is an efficient agent, although its effects are limited in time. Other materials still suffer either from a short-lasting effect or migration in distant organs. We evaluated here novel UBAs using an ex vivo model, with respect to criteria of ease of injection, ability to form a high and stable tissue bulking, implant elasticity and tissue reaction. One approach involves solutions of polymers in water-miscible organic solvents that precipitates in situ. In this manner, high and stable bulks were routinely obtained using various commercial polymers. Selected solvents reduced the tissue reaction to the implant. Microsphere suspensions in hydrogels also proved to be efficient UBA, although less stable bulks were obtained. Thermosetting chitosan hydrogels showed promising results with respect to bulk stability and isoelasticity with surrounding tissues. Different strategies have thus been compared and optimised ex vivo. Further experiments are required to compare the ability of these materials to induce a sustained in vivo bulking effect.