Urethral bulking with polymethylmethacrylate microspheres for stress urinary incontinence: tissue persistence and safety studies in miniswine.

OBJECTIVES To evaluate the safety and persistence of injectable polymethylmethacrylate (PMMA) microspheres as a long-lasting urethral bulking agent in pigs. PMMA microspheres of 2 different diameters (40 and 125 μm) were tested to investigate the potential for migration and dislocation after injection. A similar product containing 40-μm PMMA microspheres has been used as an injectable wrinkle filler for >25 years and received Food and Drug Administration approval in 2006 (ArteFill). METHODS A total of 22 female pigs received 4 submucosal implantations of PMMA microspheres, using either a cystoscope or a newly developed urethral injection device (UroScope). At death and necropsy at 8 days and 1, 3, and 6 months, the urethral injection site, liver, lung, spleen, and pelvic and iliac lymph nodes were processed for histologic examination and microsphere count using organ dissolution and microscopy. RESULTS All injected submucosal blebs were still present at 6 months and showed no signs of inflammation. Tissue dissolution of the local lymph nodes and major organs demonstrated the transport of some of the 40-μm microspheres to the local lymph nodes and lung but not to the liver or spleen. In contrast, no 125-μm microspheres were detected in any distant organ. CONCLUSIONS The submucosal implantation of 125-μm PMMA microspheres into the urethra provided a safe and persistent bulking effect in pigs. The positive results of the present study encourage additional investigation of 125-μm PMMA microspheres as a long-lasting bulking agent for the treatment of female stress urinary incontinence. Furthermore, a newly developed urethral injection device (UroScope) proved beneficial and cost-effective to facilitate the transurethral injections of 125-μm PMMA microspheres.