Is a functional urinary bladder attainable through current regenerative medicine strategies?

Cent Eur J Urol 2013; 66: 207-208 DOI: 10.5173/ceju.2013.02.art24 The concise yet poignant review article by Adamowicz et al. [1] appearing in this issue of the “Central European Journal of Urology” delves into two critical aspects of urinary bladder tissue engineering. The use of appropriate scaffolding material as an architectural foundation for bladder regeneration combined with multipotent stem/progenitor cell populations is paramount to a physiologically functional bladder. The article presents a critical review of the current state of bladder regeneration and its applicability to a variety of bladder based states including bladder cancer. The use of autologous intestinal segments as a strategy to augment poorly functioning bladders has been a surgical main stay for several decades utilized by the clinical urologist. Although this strategy does provide a stop–gap measure for those in need to increase physiological output of a potentially failing bladder, a myriad of short– and long–term complications still plague this method with the potential of providing a fatal outcome [1, 2, 3]. Tissue engineering strategies that have evolved over the last several decades for bladder regeneration have been monumental to the field undergoing multiple iterations from different researchers [4, 5]. Although many attempts have been made to create a physiologically functional bladder or replacement bladder tissue, the reality of this endeavor is still waiting in the wings. Recent clinical trial data in the United States suggests that current strategies need to be re–evaluated and honed in order to obtain optimal results [6]. As tissue engineering encompasses multiple scientific disciplines including aspects of engineering, cell biology, and medicine, the products derived from these groups must act in concert. This would lead to the creation of the optimal graft for patients in need of bladder tissue replacement. Two critical areas, in this regard, are scaffold design and the cells to be utilized in the graft. Researchers have demonstrated the use of a variety of scaffolding material including biologic based materials such as small intestinal submucosa (SIS) and bladder acellular matrix (BAM) as well as synthetic materials including poly glycolic acid (PGA) and its derivatives and the elastomer family of poly (diol citrates) (POC). Problems that have been encountered with biological materials include graft contraction issues once placed in vivo as well as material reproducibility as batch to batch variation of these materials poses a problem in the regenerating milieu. The synthetic materials that have been produced to date vary quite broadly in their chemical composition and their mechanical characteristics. The task of the chemical engineer entrusted to create a suitable scaffold should be to create a material that can not only mimic the mechanical properties of the bladder including elasticity and biaxial stretch ability but also produce a material that is biologically compatible and biodegradable. Lastly, the material should also provide a water–impermeable barrier during early phases of graft growth with the ability to allow for the simultaneous transposition of small molecules needed for induction of tissue growth and development. To date, the only published clinical trial data to use a very rigid, synthetic scaffold (PGA) demonstrated just marginal results although the study itself was highly novel in approach. Future endeavors towards scaffold design should focus upon “smart” elastomers such as POC that can truly mimic the mechanical parameters and aid in the early stages of regeneration as mechanical stimulation have been shown to be crucial in these early stages [7]. The cellular make up of the potential grafts must be considered carefully as certain biological parameters must be met in order to achieve Editorial referring to the paper published in this issue on pp. 202–206 UROLOGICAL ONCOLOGY