Bladder Substitution: The Role of Tissue Engineering and Biomaterials

Abstract

Tissue engineering could play a major role in the setting of urinary diversion. Several conditions cause the functional or anatomic loss of urinary bladder, requiring reconstructive procedures on the urinary tract. Three main approaches are possible: (i) incontinent cutaneous diversion, such as ureterocutaneostomy, colonic or ileal conduit, (ii) continent pouch created using different segments of the gastrointestinal system and a cutaneous stoma, and (iii) orthotopic urinary diversion with an intestinal segment with spherical configuration and anastomosis to the urethra (neobladder, orthotopic bladder substitution). However, urinary diversions are associated with numerous complications, such as mucus production, electrolyte imbalances and increased malignant transformation potential. In this context, tissue engineering would have the fundamental role of creating a suitable material for urinary diversion, avoiding the use of bowel segments, and reducing complications. Materials used for the purpose of urinary substitution are biological in case of acellular tissue matrices and naturally derived materials, or artificial in case of synthetic polymers. However, only limited success has been achieved so far. The aim of this review is to present the ideal properties of a urinary tissue engineered scaffold and to examine the results achieved so far. The most promising studies have been highlighted in order to guide the choice of scaffolds and cells type for further evolutions.

Porcine Small Intestinal Submucosa (SIS) as a Suitable Scaffold for the Creation of a Tissue-Engineered Urinary Conduit: Decellularization, Biomechanical and Biocompatibility Characterization Using New Approaches

“…For a urologic application, the main requirements consist of obtaining a fully impermeable scaffold that must maintain the conduit’s patency, as well as physiological compliance and elasticity. However, the need for a surface impermeable enough for the prevention of urine leakage has to be balanced with features that allow adequate cell migration, adhesion, proliferation, and differentiation [ 66 ]. Therefore, the attention was focused on SIS because of its known capability to integrate with host tissues and to promote tissue regeneration, providing the optimal environment for cell adhesion and proliferation [ 40 ].…”

“…Previously, several studies tried to assess the usefulness of tubular structures in urinary tract reconstructive urology, and many of them used acellular tissues, and in particular SIS, to create tissue engineered urinary substitutes [ 66 , 71 ]. In the case of urinary diversions, SIS has been used in a rat model, either unseeded or seeded with 3T3 fibroblasts [ 10 ].…”

A Novel Hybrid Membrane for Urinary Conduit Substitutes Based on Small Intestinal Submucosa Coupled with Two Synthetic Polymers

“…In order to prevent these complications, tissue-engineering strategies can be exploited to obtain a urinary conduit characterized by adequate impermeability, patency, compliance, and elasticity [ 52 , 53 ]. Moreover, the engineered conduit has also to allow cell migration, adhesion, proliferation, and differentiation [ 54 ].…”

Tissue Engineering and Regenerative Medicine in Pediatric Urology: Urethral and Urinary Bladder Reconstruction

“…The first aim of TE is to provide the ideal scaffold, which has to be biocompatible, biodegradable, and non-immunogenic, and it has to promote adequate blood supply, enhance cell adhesion and native-like tissue organization, and provide a substrate with similar mechanical features to those of native tissue. Specifically, with regard to urological applications, the scaffold has to provide an effective barrier against cytotoxic urine for the surrounding tissues and has to guarantee adequate mechanical features in order to resist to the cyclical filling and emptying of the urinary bladder [ 1 , 3 , 6 ]. Engineered bladders have to support urine storage while keeping contractile properties to allow physiologic voiding, and they need to reconstruct a compliant muscular wall with a highly specialized urothelium [ 7 ].…”

“…Hitherto, several TE approaches have been evaluated, starting from the choice of scaffold and followed by the choice of cell type in the case of seeded grafts [ 6 ]. In addition to the requirement of biocompatibility, biodegradability, mechanical features similar to native tissue, assistance on cell adhesion, and surgically easy manipulation for the choice of the ideal scaffold, in the case of urinary applications further requirements are crucial, including quick regeneration of the urinary barrier to minimize leaks that would heighten the local inflammatory response and appropriate mechanical resistance to sustain the mechanical forces necessary for bladder filling and emptying [ 2 , 6 , 7 , 8 , 9 ]. Moreover, in the specific case of pediatric urology, a greater regenerative capacity of the scaffold, a long life span, and no requirement for prolonged urinary diversions with catheters are crucial elements [ 1 , 3 ].…”