Total urinary bladder regeneration with restoration of native structure and pharmacological response

Abstract

Neo‐bladder histology and pharmacological response were investigated in 7 dogs at 51 (n=1), 89 (n=3), and 179 (n=3) days (d) after radical cystectomy and implantation of a Neo‐Bladder Replacement Construct (Construct). Pharmacological responses of neo‐bladder tissue strips (51, 89, and 179 d; 3, 18, and 27 strips, respectively) were compared to age‐matched native bladder (n=13; 49 strips).By 51 d post‐implantation (p.i.) regenerated bladder was histologically consistent with native bladder including mucosal and serosal linings, detrusor muscle, vascular, and nerve composition. Logistic analysis revealed similar EC50 and slope factor values for contraction of bladder tissue strips derived from all groups induced by carbachol (Car) and electrical field stimulation (EFS). A statistically significant and progressive increase in the mean Emax values occurred in response to both Car and EFS over time. While contractile responses to Car and EFS increased over time, they were lower than native bladder responses at 51 and 89 d p.i. Car‐induced contractions, but not EFS‐induced contractions, were equivalent to native tissue at 179 d p.i.A Neo‐Bladder Replacement Construct is capable of regenerating urinary bladders in vivo with histological and pharmacological responses similar to native bladder by 179 d p.i. There was no evidence of abnormal cell growth, immune response, or adverse systemic effects.