Development of a cell-seeded modified small intestinal submucosa for urethroplasty

Objective: To explore the feasibility of a modified 3D porous small intestinal submucosa (SIS) scaffold seeded with urothelial cells (UC) for surgical reconstruction in a rabbit model. Material and methods: Eighteen New England white male rabbits were divided into three groups and a 0.8 × 1.5 cm2 section of the anterior urethral mucosa was removed from each animal. Ventral onlay urethroplasty was performed with a 1.0 × 1.7 cm2 SIS scaffold that was either cell-seeded and treated with 5% peracetic acid (PAA) (n = 6), or cell-seeded and untreated (n = 6), or unseeded and treated with 5% PAA (n = 6). Animals were sacrificed at 6 months post-repair and retrograde urethrography and histological analyses performed. Results: In animals implanted with cell-seeded and PAA treated SIS scaffolds, urethrography showed wide-caliber urethra without any signs of stricture or fistulae, and histological analyses confirmed a complete urethral structure. In contrast, ulceration and fistula occurred in the reconstructed urethra of animals implanted with cell-seeded but untreated SIS scaffolds, and evident stricture was present in the unseeded, PAA treated group. Histological analyses demonstrated less urothelial coverage and smooth muscle in the cell-seeded and untreated SIS scaffold group, and serious fibrosis formation occurred in the unseeded, treated group. Conclusions: A modified 3D porous SIS scaffold seeded with UC and treated with PAA produces better urethroplasty results than cell-seeded untreated SIS scaffolds, or unseeded PAA treated SIS scaffolds.