Videofetoscopically Assisted Fetal Tissue Engineering: Bladder Augmentation By Dario 0. Fauza, Steven J. Fishman, Kathryn Mehegan, and Anthony Atala Boston, Massachusetts Background/furBose:Treatment of several congenital anoma- lies is frequently hindered by lack of enough tissue for surgical reconstruction in the neonatal period. Minimally invasive harvest of fetal tissue, which is then processed through tissue engineering techniques in vitro while preg- nancy is allowed to continue so that at delivery a newborn with a prenatally diagnosed congenital anomaly can benefit from having autologous, expanded tissue promptly available for surgical reconstruction at birth. This concept was applied to a bladder defect. Methods: Bladder exstrophy was surgically created in ten 90- to 95-day gestation fetal lambs, which were divided in two groups. In group I, a small fetal bladder specimen was harvested through a minimally invasive technique (videofe- toscopy). Urothelial and smooth muscle cells were then separately cultivated and expanded in vitro for 55 to 60 days, resulting in a total of approximately 200 million cells. Seven to IO days before delivery, the cells were seeded in two layers in a 16. to 20-cm’, 3-mm thick biodegradable polyglycolic acid polymer matrix. One to 4 days after delivery, autologous engineered tissue was used for surgical augmentation of the exstrophic bladder. In group II, no harvest was performed, and the bladder exstrophy was primarily closed after deliv- ery. In both groups, a catheter was left inside the bladder for 3 weeks, at which time a cystogram was performed and the catheter then removed. In all animals, at 60 days, another cystogram was performed and urodynamic studies of the bladder were performed. The bladder was then removed for histological analysis. Results: Fetal survival rate was 100%. One newborn died immediately after the implantation of the engineered bladder from an anesthetic accident. The other nine (four in group I and five in group II) survived. One of the animals from group I lost its bladder catheter prematurely and had a urinary leak detected only at the time of death. There were no other complications. The engineered bladders were more compli- ant (P < .05) and had greater capacity pressures greater than 20 mm Hg (P< .05) than those closed primarily. Histological analysis of the engineered tissue showed a multilayered urothelial lining on the luminal side and overlying layers of smooth muscle cells surrounded by connective tissue. Conc/usions: Videofetoscopically assisted fetal bladder engi- neering may be a viable alternative for prompt bladder reconstruction at birth. The architecture of autologous engi- neered fetal bladder tissue resembles that of native bladder. This concept may prove useful for the treatment of certain human neonatal conditions such as bladder and cloaca1 exstrophies. J Pediatr Surg 33:7-12. Copyright o 1998 by W.B. Saunders Company. INDEX WORDS: Fetal surgery, tissue engineering, videofetos- copy, bladder exstrophy, bladder, congenital anomalies, trans- plantation. B IRTH DEFECTS entail loss or malformation of tissues or organs.The definitive treatment of many congenital anomalies at birth is often impeded by the scarce availability of normal tissues or organs, either autologous or allologous. The severe donor shortage observed in practically all areas of transplantationis even more critical during the neonatal period. Likewise, autolo- gous grafting is frequently not an option in newborns because of donor site size limitations. One of the purposes of the present study was to introduce a novel concept in perinatal surgery involving minimally invasive harvest of fetal tissue, which is then engineeredin vitro while pregnancy is allowed to con- tinue. The newborn with a prenatally diagnosed birth defect can benefit then from having autologous, ex- panded tissue promptly available for definitive surgical treatment in the neonatal period. This concept was applied to an experimental bladder defect. Other objec- tives were the analysis of an engineered fetal bladder graft after implantation in the neonateaswell as the study JournalofPediatric Surgery, Vol33, No 1 (January), 1998: pp 7-12 of the responseof fetal urothelial and detrusor muscle cells when submittedto tissue engineeringtechniques. MATERIALS AND METHODS The Harvard Medical School animal management program is accred- ited by the American Association for the Accreditation of Laboratory Animal Care (AAALAC file # 000009) and meets National Institutes of Health standards as set forth in the Guide for the Care and Use of Laboratory Animals (National Research Council mtblication, Revised 1996). From the Harvard Center for Minimally Invasive Surgery and the Departments ojSurgely and Urology, Children’s Hospital and Haward Medical School, Boston, MA. Presented at the 44th Annual International Congress of the British Association of Paediatric Surgeons, Istanbul, Turkey, July 22-2.5, 1997. This research was supported in part by a grantfrom the United States Surgical Corporation and American Medical Systems. Address reprint requests to Anthony Atala, MD, Children’s Hospital, Hunnewell 3, 300 Longwood Ave. Boston, MA 02115. Copyright o 1998 by WB. Saunders Company 0022.3468/98/3301-0002$03.00/O 7