Regeneration of functional bladder substitutes using large segment acellular matrix allografts in a porcine model

Purpose: We previously reported on the short-term (4 weeks) morphometric an alysis of a large bladder acellular matrix allograft used as a bladder biop rosthesis (average size 24 cm.(2)). We demonstrated cellular repopulation t hrough the entire thickness of the graft. We now present the long-term (12 weeks) morphometric results of graft regenerated porcine bladders using seg ments measuring an average of 40 cm.(2). Materials and Methods: Bladders harvested from pigs were subjected to deter gent and enzymatic extractions to render them acellular. Partial cystectomy was performed in 21 pigs and the defect was repaired with a bladder acellu lar matrix allograft (average size 40.52 cm.(2)). Of the animals 8 were sac rificed at 1, 2 and 4 weeks and 13 were sacrificed at 8 and 12 weeks. To ev aluate cellular repopulation and matrix reorganization the native bladder a nd graft were analyzed using standard histological and immunofluorescent te chniques. To evaluate for calcium deposits in the grafts a radiological eva luation of the graft was performed after explantation. Results: All animals survived the surgical procedure and there were no sign ificant urinary leaks. No stones were noted in any of the bladders. At 1 we ek there was a diffuse infiltration with acute inflammatory cells, At 2 wee ks the luminal surface of the graft was lined with a single layer of urothe lium, and there was stromal infiltration with unorganized smooth muscle cel ls and angiogenesis. At 4 weeks the urothelium was multilayered with organi zing groups of smooth muscle cells and angiogenesis. At 8 and 12 weeks ther e was repopulation throughout the bladder acellular matrix allograft implan t with all native cellular components participating. Conclusions: We present evidence that large patch bladder acellular matrix allograft implantation is technically feasible and may prove to be a viable surgical alternative to bladder augmentation with intestinal segments. Its advantages may include the potential for complete and functional regenerat ion of a bladder substitute.