Local and Systemic Effects of a Tissue Engineered Neobladder in a Canine Cystoplasty Model

Abstract

Tissue engineered bladders are emerging as a potential treatment option in urological surgery. Although successful neobladders can be engineered with autologous cells on a biodegradable polymer scaffold, studies of the local and systemic effects on host tissue have not been extensively pursued. We examined such effects at predetermined time points after implantation of tissue engineered neobladders in a canine cystoplasty model. Eight dogs underwent trigone sparing cystectomies. Six dogs (experimental group) received bladder augmentation with tissue engineered constructs produced from autologous urothelial and smooth muscle cells on a prefabricated polyglycolic acid polymer scaffold. Two beagles (control group) received bladder augmentation with the polyglycolic acid scaffold alone. Serial urodynamic studies, cystograms, peripheral blood smears, urinalysis, serum chemistry, complete blood count and electrolytes were done at predetermined time points postoperatively. The bladder, and local and distant organs were retrieved 6 months after surgery for analysis. Capacity and compliance of the engineered bladders reached normal levels by 6 months. Engineered bladders showed tissue composition similar to that of normal bladders. Infiltration of inflammatory cells was minimal and subsided with time. An increase in the total systemic leukocyte count and in bacteriuria was evident initially at 1 week but they returned to normal levels by 1 month postoperatively. Other systemic parameters remained within normal levels at all time points. There was no evidence of abnormal findings in local or distant organs. Implantation of polymer molds seeded with autologous bladder cells did not show significant local or systemic toxicity in a canine model. This study suggests that such engineered neobladders are safe and effective for reconstructive surgery.