Cell-seeded tubular acellular matrix for replacing a long circumferential urethral defect in a canine model: Is it clinically applicable?

Objective: To evaluate the feasibility of replacing a relatively long segment of the canine urethra by a tube of cell-seeded acellular collagen bladder matrix.

Materials And Methods: The study included 14 female mongrel dogs in which a 3-cm segment of the whole urethral circumference was excised and replaced by a tube of acellular matrix seeded with autologous urothelial cells. The acellular matrix was obtained from the excised bladder of female donor dogs that were not included in the study. Autologous cells were obtained from the study dogs by open bladder biopsy, with subsequent in vitro expansion and cultivation. Urethroplasty was performed over a 16 F urethral catheter that was kept for 4 weeks. The dogs were killed humanely (one every week for 4 weeks and then one monthly for 10 months). After stent removal, retrograde urethrography was used each month in the living dogs. If retention occurred a urethrogram was taken and then the dog was killed humanely. All grafts from dogs were harvested and sent for histopathological examination.

Results: Exploration at 1, 2, 3 and 4 weeks showed progressive shrinkage in length, together with relative narrowing of the lumen. Three dogs developed retention within a week after stent removal and the other seven developed retention within 4 months. Retrograde urethrograms showed evidence of stricture and/or fistula at the graft site in all dogs. On exploration, grafts showed marked shrinkage (0.6-1.2 cm in length) with complete obliteration of their lumens. Histopathological examination showed extensive fibrosis of the matrix with no evident urothelial architecture.

Conclusion: Cell-seeded acellular matrix tube is insufficient to replace a 3-cm circumferential urethral defect in dogs.