Safety and Feasibility Study of Autologous Engineered Urethral Constructs for the Treatment of Strictures

This is a Phase I clinical study to determine the safety and efficacy of using autologous, engineered urethral constructs for the treatment of urethral strictures in adult males. The proposed study design is a prospective non-randomized and uncontrolled single-center investigation. Autologous urothelial cells (UCs) and smooth muscle cells (SMCs), obtained from enrolled male subjects' bladder tissue samples, will be culture expanded in vitro and used to seed tubular PGA scaffolds to create autologous urethral constructs for the repair of urethral strictures.

Inclusion Criteria: * Stricture of the urethra meeting the following criteria: a) History of at least one 15-60 mm in length, as determined by urethrography. c) Contains at least 1 strictured segment through which a 16 Fr flexible cystoscope cannot be atraumatically passed. * Patients must be available for all follow-up visits. * Ability to speak English. Exclusion Criteria: * Strictures of the meatus or prostatic urethra; any urethral stricture associated with or suspected to be urethral carcinoma, or strictures due to pelvic distraction injuries. Strictures \60 mm, as determined by urethrography, and criteria for bulbar urethral strictures excluding those with strictures \60 mm, as described by urethrography. * Presence of untreated urinary tract infection. * Presence or prior history of lichen sclerosis et atrophicus (previously termed 'balanitis xerotica obliterans'). * Uncontrolled bleeding disorder or patients with a platelet count less than 50,000, hemophilia or patients routinely receiving blood products for bleeding disorders. * Any urological condition that would be likely to require additional urethral instrumentation during the period of investigation, including, but not limited to benign prostatic hyperplasia requiring treatment, use of alpha blockers, active prostate cancer, an unevaluated elevated prostate surface antigen (PSA), bladder cancer, or any recurrent urinary stone formation. Patients with evidence or diagnosis of any coagulation disorder (including concomitant anti-coagulation therapy at enrollment). * Serum creatinine \> 2.0 mg/dl or evidence of progressive renal disease. * Patients with abnormal urologic conditions, including vesicoureteral reflux, bladder stones, bladder tumors and renal impairment. * Subjects with an alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value \>3 times the upper limit of normal. * Subjects with an albumin value \