The review article by Arun Sharma in this issue of Regenerative Medicine [1] highlights the successes of the different disciplines involved in regenerative medicine for the purpose of urinary bladder tissue engineering. It is rich and diverse in presenting the multiple facets that we need to address to have a successful outcome (i.e., a compliant and contractile urinary bladder). The authors present a clear, detailed summary of all the aspects that we need to take into account when we attempt to regenerate or tissue engineer a bladder. However, while it is evident that this task has resulted in many breakthrough findings [2,3], they have yet to culminate in an effective and clinically tested tissue engineered construct that meets the expectations of healthcare providers and surgeons. The key reason for the multiple failures encountered in this field could be related to the fact that we are still in some ways simplistic in our approach; the bladder may be forgiving but it is not a simple organ that can be easily replaced and regenerated. Much can be learned from bladder development, injury and the remodeling to help understand how to rebuild the bladder in vitro. The signaling pathways involved in the cellular and molecular mechanisms underlying bladder development and injury-induced regenerative response may have immense potential in designing strategies for urinary bladder regeneration [4]. Unfortunately, none of the lessons learned in this area have been translated into tissue engineering research. The two areas that have been thoroughly studied in the tissue engineering field are biomaterial science and cell biology. Although we may be closer to identifying a suitable biomaterial, we have not yet taken into account the many factors that may predispose biomaterials to fail as a bladder substitute. The most common reason for failure is porosity, which is thought to be a valuable indicator for adequate cellularization. On the other hand, when we aim to replace an impermeable organ such as the bladder, permeability/porosity may hinder cellularization, with urine halting repair and causing fibrosis. Moreover, the mechanical properties of the biomaterials may have been well investigated prior to implantation, but the minor and minute changes in the architecture of those biomaterials upon implantation will have major impact on their mechanical properties, thus limiting their use as a bladder-replacement technology [5]. Finally, although biomaterials are noncellular and hence nonimmunogenic, recent literature suggests that allogenic natural scaffolds and possibly collagen-based synthetic scaffolds may induce an immune response that is innate in nature [6,7]. This immune response may cause fibrosis and induce histological changes that are detrimental. In terms of cell biology, with or without scaffolds, a plethora of literature is available on the adhesion properties, proliferation and differentiation characteristics of urinary bladder cells on different natural and synthetic scaffolds. On the other hand, it is well known that once cells are removed from an organ and are grown in vitro, they dedifferentiate and require complex environmental cues and factors to get them to differentiate into relevant cells types, whether it be urothelial cells as an impermeable layer or smooth muscle cells as a major component for the unique mechanical properties of the bladder. The importance of this differentiation process is emphasized by the fact that bladders that are not adequately cycled during fetal life tend to end up being abnormal when the children are born. Cell-seeded scaffolds need specific fine tuning not only with growth factors or cytokines, but
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Apr 25, 2020
Xiuzhen Zhang + 3
Open Access