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Nanotechnology for Tissue Regeneration
Published in Bhaskar Mazumder, Subhabrata Ray, Paulami Pal, Yashwant Pathak, Nanotechnology, 2019
Kumud Joshi, Pronobesh Chattopadhyay, Bhaskar Mazumder
Kidney failures and renal disease are the commonest serious health problems associated with advanced age. Tissue engineering research for kidney transplantation and restorative purposes is well underway and scaffolds have been successfully developed and tested on animal models. Different groups have been involved in kidney and lower tissue scaffold engineering. Ross et al. (2009) demonstrated the capability of embryonic stem cells to differentiate into kidney cells in suitable ECM. Song et al. (2013) successfully engineered ectopic kidney tissue using a decellularized matrix; these grafts produced rudimentary urine in vitro when perfused through their intrinsic vascular bed. When transplanted in an orthotropic position in the rat, the grafts were perfused by the recipient’s circulation and produced urine through the urethral conduit in vivo, successfully demonstrating the potential of the development of a functional kidney. PCL-based, electrospun scaffold for the proliferation of human kidney epithelial cells has been investigated and the diameter of the nanofibers is known to play a crucial role in the differentiation of the cells (Burton et al., 2018). Similarly, advancements in the field of bladder tissue grafts are also underway and 3D nanografts utilizing urothelial cells, smooth muscle cells, and vascular growth factors have shown promising results in repairing bladder damage (Ling et al., 2017).
Mechanobiology of Bladder Urothelial Cells
Published in Jiro Nagatomi, Eno Essien Ebong, Mechanobiology Handbook, 2018
Shawn Olsen, Kevin Champaigne, Jiro Nagatomi
The urothelium is the epithelial lining of the urinary bladder, and recent discoveries have suggested that in addition to providing a barrier to urine, the urothelium actively participates in sensory functions related to thermal, chemical, and mechanical stimuli and releases chemical signals in response [8–11]. Ion channels have been proposed as part of a potential transduction mechanism for this function of the urothelium [12]. Thus far, despite the identification of numerous proteins as potentially mechanosensitive, the mechanism by which these proteins transduce mechanical stimuli into biochemical signals that produce a cellular response is still unknown [13]. In this chapter, we will first discuss the role that urothelial cells play in normal bladder physiology. We will then review the current theories of urothelial cell mechanotransduction involving mechanically triggered adenosine triphosphate (ATP) release and activation of membrane-bound ion channels, which may contribute to the bladder's ability to sense fullness and communicate with the nervous system. By determining the specific mechanisms by which urothelial cells participate in bladder physiology and pathophysiology, it is believed that further strides can be made toward the development of effective treatments for LUTS.
Bladder Tissue Engineering
Published in Gilson Khang, Handbook of Intelligent Scaffolds for Tissue Engineering and Regenerative Medicine, 2017
At the microscopic level the bladder is composed of the urothelium, the detrusor muscle (consisting of three layers of smooth (involuntary) muscle fibers: the external layer with fibers arranged longitudinally, the middle layer with fibers arranged circularly, and the internal layer with fibers arranged longitudinally), blood vessels, and nerves. The urothelium is a specialized transitional epithelium which serves as a barrier for urine. In contrast to other epithelia, it does not secret mucus. The urothelium is composed of three cell layers: basal, intermediate, and superficial cell layers (see Fig. 33.2a). Superficial cells (also known as umbrella cells) form a barrier against waste products excreted by the kidneys. These cells can stretch toward an elliptical shape when the bladder is filled (Fig. 33.2b). Basal cells are cylindrical or flat when the bladder is filled (Fig. 33.2c). Cells from the superficial cell layer are frequently exfoliated into the urine. Urothelial cells maintain a slow turnover rate but most of the urothelial cells are quiescent.2 However, after infection these cells become highly proliferative.3,4
Computational modeling of stretch induced calcium signaling at the apical membrane domain in umbrella cells
Published in Computer Methods in Biomechanics and Biomedical Engineering, 2023
Amritanshu Gupta, Rohit Manchanda
The urothelium is the epithelial tissue lining the luminal surface of the urinary bladder. Its superficial layer comprises a specialised monolayer of polyhedral cells known as the umbrella cells (UCs), which form the interface between the urine and the underlying layers of the bladder wall. In addition to being a physical and protective barrier, the superficially placed UCs are involved in the transduction of various stimuli present in their external milieu, i.e., the urine (Khandelwal et al. 2009; Birder and Andersson 2013). These stimuli include mechanical stretch, change in temperature and alteration in the levels of chemical metabolites. UCs are highly polarised, having distinct apical and basolateral membrane domains designed to perform highly specialised and localised signaling functions (Khandelwal et al. 2009). More specifically, it is the apical membrane domain of the umbrella cell (UC) where key signal transduction activities are triggered.
Constructing artificial urinary conduits: current capabilities and future potential
Published in Expert Review of Medical Devices, 2019
Jan Adamowicz, Shane V. Van Breda, Tomasz Kloskowski, Kajetan Juszczak, Marta Pokrywczynska, Tomasz Drewa
Success in artificial urinary conduit construction will depend on the appropriate scaffold production. The major challenge is to obtain an alternative material mimicking a natural ECM which would integrate with the host tissue and promote healthy cellular behaviors [34]. The ideal biomaterial for urinary tract reconstruction should support attachment of urothelial cells and their linear propagation aimed to build the barrier preventing absorption of urine. The scaffold should also undergo degradation after completion of the remodeling phase in order to not affect the passive biomechanical characteristic of neo-tissue. Scaffold debris must be non-toxic to the cells and immunogenically low to omit inducing chronic inflammatory responses responsible for severe scarring [35]. The environment of the urinary tract is unfavorable for cells due to the presence of urine which showed cytotoxic effects on mesenchymal stem cells, urothelial and smooth muscle cells [36,37]. The scaffold should be optimized for being used in reconstructive urology, protecting cells from urine, at least shortly after implantation when the urothelial layer does not exist, and urine directly damages cells. A solution might be to create a degradable layer on the inner side of the biomaterial which would protect immature urothelial cells before the stratification process with uroplakin completes. The urinary tract wall comprises many different cell types that work together to preserve optimal function. The artificial conduit is, in fact, a living system comprising a cellular and biomaterial component. The 3D biomaterial architecture must support cell migration and communication by providing an appropriate adhesive surface. The biomaterial size is a crucial parameter. If pores are too small cells cannot migrate in towards the center of the construct limiting the diffusion of nutrients and removal of waste products. Conversely, if pores are too large, there is a decrease in specific surface area available, limiting cell attachment [38]. It has been shown that the optimal pore size for biomaterials designed for tissue engineering ranges from 50 to 500 mm [39]. Based on these defined technological requirements, during the last decade of different research biomaterials were evaluated for urinary conduit production. Decellularized tissues (such as small intestinal submucosa, bladder acellular matrix) were evaluated as they are cost-effective and characterize with an excellent biocompatibility profile [40].