Xenogenic extracellular matrices as potential biomaterials for reconstruction of the urinary bladder.

Surgical repair for end stage bladder disease often utilises vascularised, autogenous, mucus-secreting gastrointestinal tissue to either replace the diseased organ or to augment inadequate bladder tissue. Postoperatively, the compliance of the bowel is often sufficient to restore the basic shape, structure and function of the urinary bladder, however lifelong postoperative complications are common. Comorbidities that result from interposition of intestinal tissue are classified as metabolic or neuromechanical and their incidence approaches 100%. The debilitating comorbidities and inherent limitations associated with these urological procedures may be mitigated by the availability of alternative, readily available, animal derived extracellular matrix (ECM) scaffolds. ECMs are decellularised, biocompatible, biodegradable biomaterials usually derived from porcine organs. This thesis aims to investigate the potential for replacing and augmenting defective bladder tissue with a biocompatible, porcine derived ECM scaffold in place of autogenous gastrointestinal tissue. In this thesis I found that ECM scaffolds possess important biomechanical limitations for bladder reconstructive purposes. Implantation of ECM into ovine bladder models resulted in significant decreases in bladder capacity and compliance. Therefore, a novel ‘surface-area’ was developed to prevent these biomechanical complications from occurring. After applying this concept to bladder models, results demonstrated that an increase in ECM scaffold surface-area relative to the resected segment of gastrointestinal tissue leads to improved capacity and compliance values after bladder augmentation. The biological properties of two different FDA approved ECM scaffolds were also investigated with particular emphasis on their urological regenerative potential. Findings demonstrated that porcine urinary bladder matrix (UBM) demonstrates significantly greater regenerative potential for bladder tissue compared to porcine small intestinal submucosa (SIS). However, exposure of both ECM scaffolds to a simulated in vivo urine environment significantly impaired their ability to induce effective urothelial regeneration. This led to the development of an in vitro bladder bioreactor that mimicked the urinary bladder’s physiological environment. The bioreactor facilitated the growth of a stratified urothelium on the ECM’s surface and therefore protected the scaffold against the cytotoxic effects of urine prior to in vivo implantation. Findings from this thesis may have important clinical implications as metabolic, infective and malignant complications precipitated by autogenous mucus-secreting epithelium are avoided with porcine ECM scaffolds.