Urinary Diversions After Radical Cystectomy: Realization of Conduits and Bladder Replacement Using Tissue Engineering Techniques

Several diseases and conditions can severely affect the urinary system, such as bladder cancer, congenital malformations, and ureteral stenosis, often necessitating surgical intervention, including tissue or organ replacement. Current clinical approaches rely predominantly on autologous intestinal grafts, which are associated with significant complications and fail to replicate the functionality of native urinary tissues. In this context, tissue engineering offers a promising solution by enabling the development of patient-specific, ready-to-use scaffolds. This doctoral research investigates innovative bioengineering strategies to address these challenges by developing decellularized scaffolds from porcine tissues tailored for specific urological applications. The study evaluates in vitro the potential of four constructs: (1) a hybrid conduit combining decellularized small intestinal submucosa (SIS) with polycarbonate urethane for urinary diversions and (2) decellularized descending aorta as alternative urinary conduits to use as urinary diversions, (3) decellularized porcine ureter for partial or total ureteral repair, and (4) decellularized porcine urinary bladder for bladder augmentation. Quantum Molecular Resonance (QMR) technology was employed to create micro-perforations in the urinary bladder scaffold, facilitating future cell migration and tissue regeneration. Histological analyses confirmed the effective decellularization of all tissues, with efficient cell removal while preserving key extracellular matrix (ECM) components such as collagen fibers and glycosaminoglycans. The hybrid conduit demonstrated improved mechanical resistance without altering tissue composition, as confirmed by FTIR-ATR and two-photon analyses. Cytocompatibility studies revealed enhanced cell adhesion and proliferation on the hybrid scaffold compared to SIS alone. The descending aorta exhibited high mechanical strength and favorable cell growth potential, while the ureter and bladder studies identified optimized decellularization protocols preserving ECM integrity. For the urinary bladder, micro-perforated scaffolds were successfully created. Additionally, electrical impedance characterization was performed to support process standardization and industrial scalability. These findings lay a robust foundation for future in vivo studies and highlight the potential of these constructs as viable alternatives to traditional approaches, with the ultimate aim of improving patient outcomes and reducing reliance on autologous grafts.