In vivo bladder regeneration using small intestinal submucosa: experimental study

Abstract

Significant side effects are correlated with bladder augmentation. Recently, small intestinal submucosa (SIS) has been proposed for clinical use. The efficacy of SIS bladder regeneration was studied in a porcine experimental model. Partial cystectomy (40–60% of bladder wall) was performed and replaced by SIS graft. Animals were planned to be killed at 2 weeks, 5 weeks and 3 months. Bladder capacity at 40 cmH₂O pressure and macroscopic graft morphology were assessed before and after SIS implant. Histological examination was carried out with computer assisted morphometric analysis for collagen/smooth muscle ratio. Student’s t test was adopted for statistical analysis. Two piglets died on the 9th and 10th post-operative day due to urinary peritonitis. The remaining piglets were killed after uneventful post-operative period at 5 weeks (two animals) and 3 months (two animals). The bladder capacity was reduced (−18%) at the 5 week follow-up and quite similar to the pre-operative volume (+2.5%) at the 3 months control. No diverticular formation, bladder calculi, mucus and urinary infection were found. The SIS graft resulted not significantly contracted. Histology at 10 days showed SIS membrane lined by transitional epithelium islands with some capillaries. At 5 weeks, transitional epithelium was fully covering the graft; new blood vessels and fibroblasts with smooth muscle cells were observed. At 3 months, the SIS was not evident. Two layers were defined: inner transitional epithelium, outer collagen with fibroblasts and muscular bundles. Computer assisted morphometric analysis showed collagen/muscle ratio 70/30% (normal bladder=56/44%, P<0.05). The SIS was effective as a scaffold for bladder wall regeneration in four out of six animals. Long-term studies are required to confirm the efficacy of the newly developed wall and for eventual clinical use.