Cells for Urethral Tissue Engineering

Version	Summary	Created by	Modification	Content Size	Created at	Operation
1		Cristian Pablo Pennisi	--	2656	2022-11-24 11:38:42	\|
2	Header format change	Cristian Pablo Pennisi	Meta information modification	2656	2022-11-24 11:39:52	\| \|
3	format correct	Vivi Li	-31 word(s)	2625	2022-11-25 07:37:18	\|

This entry is adapted from the peer-reviewed paper 10.3390/ijms232214074

Urethral stricture is a common urinary tract disorder in men that can be caused by iatrogenic causes, trauma, inflammation, or infection and often requires reconstructive surgery. The current therapeutic approach for complex urethral strictures usually involves reconstruction with autologous tissue from the oral mucosa. With the goal of overcoming the lack of sufficient autologous tissue and donor site morbidity, research has focused on cell-based tissue-engineered substitutes. While the main focus has been on autologous cells from the penile tissue, bladder, and oral cavity, stem cells from sources such as adipose tissue and urine are competing candidates for future urethral regeneration due to their ease of collection, high proliferative capacity, maturation potential, and paracrine function.

urology urethra mesenchymal stem cells smooth muscle cells keratinocytes urine-derived stem cells

1. Introduction

Urethral stricture is a urinary tract disorder with an estimated incidence of 0.6% in men, which can be the result of a variety of factors, including trauma, infection, and iatrogenic causes ^[1]. Common to all of these conditions is that the formation of fibrous scar tissue narrowing the urethral lumen can lead to symptoms such as incomplete bladder emptying, increased frequency of urination, and difficulty or pain with urination, all of which negatively impact the patient’s quality of life. If left untreated, strictures can lead to complications such as incontinence, urinary tract infections, or even kidney failure ^[2]. In recent decades, the prevalence of strictures has remained at historically high levels. According to statistics, the total cost of urethral strictures in the United States is more than $6000 per affected person, with annual medical costs of nearly $200 million in 2009, and spending is currently much higher ^[3]. Because urethral stricture imposes a significant social and economic burden on individuals, families, and the health care system, the medical community has turned its focus to finding new therapeutic solutions.

The current gold standard for the treatment of complex urethral strictures is urethroplasty with oral mucosa ^[4]. Oral mucosa has many properties that make it particularly suitable for urethral reconstruction, as it adapts well to the moist environment of the urethra, has high mechanical strength, and can be rapidly vascularized by blood supply from the wound bed. It is also easy and quick to harvest, has a hidden suture line, and can lead to long-term success rates of 80–85% ^[5]. However, only a limited amount of oral mucosa is available for harvesting, and complications such as bleeding at the donor site, infection, pain, parotid duct injury, graft contracture, and numbness may occur ^[6]^[7].

Tissue engineering is a promising approach to compensate for the lack of autologous tissue and can avoid the complications associated with harvesting of the grafts ^[8]^[9]^[10]. Tissue engineering approaches often require biodegradable scaffolds that can serve as guidance and structural platforms for progenitor and stem cells to regenerate tissue ^[11]. The simplest tissue engineering strategy for urethral reconstruction involves cell-free natural or synthetic scaffolds ^[12]. Host cells infiltrate the scaffolds, which are remodeled and eventually replaced by the target tissue ^[13]. However, the success of acellular grafts depends on a healthy urethral bed, adequate vascularity, and the absence of spongy fibrosis. Otherwise, graft shrinkage, inadequate tissue regeneration, and uncontrolled fibrotic tissue formation may occur ^[14]. Since the underlying pathologic process in stricture disease is ischemic spongy fibrosis, the quality of the wound bed may be compromised ^[15]. Furthermore, this simple strategy can only be used as a backup option in patients with short to moderate urethral defects, as clinical data show that failures are common in patients with long strictures (>4 cm) ^[16]. For the treatment of complex strictures, cell-based tissue-engineered constructs have been investigated. A systematic review has shown that cell-based grafts have a 5.7-fold higher long-term success rate than unseeded grafts ^[9]. Notably, cell-loaded grafts have been shown to reduce the incidence of strictures, fistulas, and infections ^[14]. The most likely explanation is that cellularization may promote vascularization and urothelial barrier formation, both of which can effectively reduce local inflammation and fibrosis caused by urine leakage ^[11]. Therefore, the selection of the appropriate cell type in conjunction with a supportive scaffold is a crucial step in tissue engineering for urethral reconstruction ^[17]. While the use of cell-loaded scaffolds appears promising for the repair of complex urethral strictures, the optimal conditions for cell maturation and differentiation are still not well understood.

2. Overview of the Structure and Function of the Male Urethra

The urethra’s primary function is to transport urine from the bladder for excretion from the body and, in males, to serve as a conduit for sperm ^[18]. The bulbar and penile urethras are found in the anterior portion of the urethra, which is also known as the spongy urethra because it is surrounded by the corpus spongiosum. The urethral epithelium and lamina propria (mucosa), submucosa, and muscle layer are histologically present in the spongy urethra. The epithelial layer of the urethra acts as a highly impermeable barrier to the toxic substances contained in urine, and its histological profile varies from segment to segment. While the mucosa near the bladder neck consists of transitional epithelium, the anterior urethra is lined by pseudostratified columnar epithelium, and the external orifice (meatus urethralis) is lined by stratified squamous epithelium ^[18]. The bulbar urethra is small and fixed, whereas the penile urethra is long and mobile. Its length varies with the length of the penis, stretching up to 40% of its original length during erection ^[19]. The muscle layer is made up of smooth muscle cells and is surrounded by the outer circular and inner longitudinal muscle layers. Various cell types play an important role in maintaining the functionality of the urethra, as remodeling of the extracellular matrix (ECM) after the injury occurs largely through a coordinated interaction between smooth muscle cells, fibroblasts, and macrophages. Mechanical signals appear to play an important role in maintaining cell phenotype and expression of ECM components ^[20].

3. Sources of Differentiated Cells

A variety of cell sources have been used to engineer urethral tissue constructs. In general, these sources fall into two categories: differentiated cells and stem cells. Figure 1 provides an overview of the various sources that researchers have used or propose to use for urethral tissue engineering. Differentiated cells are cells in the final stage of differentiation, although they may undergo phenotypic changes under certain conditions (e.g., in vitro culturing). Differentiated cells for urethral reconstruction mainly comprise mature cells obtained from the penile tissue, bladder, and oral cavity, including epithelial, fibroblasts, epidermal, mesothelial cells, endothelial cells, and smooth muscle cells.

Figure 1. Schematic overview of the different tissue sources for cells relevant to urethral tissue engineering. The sources are divided into two categories: differentiated cells and stem cells.

4. Cell Preconditioning Approaches

A number of preconditioning and engineering strategies have been developed in recent years with the goal of maintaining cell viability, improving cell survival, enhancing cell maturation and differentiation, and promoting angiogenesis. Some of the most prominent are dealt with in more detail below.

4.1. Biomimetic Microenvironmental Approaches

It is desirable for any urethral engineering application that the biopsy samples are best possible protected en route from the donor. With this in mind, researchers have recently demonstrated that the transport of oral tissue samples using thermoreversible gelation polymers provides an optimal environment for preserving the viability of oral epithelial cells intended for tissue-engineered grafts ^[21]. Scaffolds that mimic the natural physical environment of cells are also critical to support cell survival, attachment and synthesis of ECM, prevent apoptosis, and facilitate cell migration. In this context, nanofibrous scaffolds fabricated by electrospinning of biopolymers provide an architecture that mimics the ECM and enables the incorporation of relevant biomolecules during the fabrication process ^[22]^[23]. Wang and coworkers have demonstrated the successful reconstruction of the urethra in a rabbit model using poly-L-lactic acid (PLLA) scaffolds seeded with ASCs ^[24]. Electrospun silk fibroin scaffolds have also shown excellent results in urethral reconstruction ^[25]. Interestingly, three-layer electrospun scaffolds that mimic the architecture of the native urethra seeded with oral fibroblasts and keratinocytes not only supported better cell attachment and proliferation but also possessed the mechanical properties of natural tissue ^[26].

Natural scaffolds obtained by the decellularization of tissues may also provide an inductive environment to support cell attachment and maturation prior to implantation. In a preclinical study, type I collagen cell carriers (CCC) with stratified multilayered autologous urethral epithelium were used to perform urethroplasty in minipigs ^[27]. The implanted grafts successfully integrated into the host with concomitant development of junctional complexes and differentiation, suggesting that the collagen matrix may improve graft stability. Although the results of using scaffolds that mimic the native architecture of the urethra are promising, it must be emphasized that most preclinical studies have been performed in animal models with transient urethral defects. However, these animal models are very different from patients in whom the pathogenic condition for urethral stricture is scarring of the corpus spongiosum leading to fibrosis.

4.2. Surface Modification and Cell Seeding Technology

Despite the encouraging results obtained so far with unmodified synthetic and natural scaffolds in the field of urethral regeneration, new preconditioning strategies, such as the incorporation of bioactive molecules and the optimization of cell seeding technology are being considered. One such strategy is to functionalize the surface of synthetic scaffolds with naturally occurring ECM molecules or peptide sequences to enhance cell adhesion. Using this approach, Uchida and coworkers modified the surface of polycarbonate-urethane-urea scaffolds, known to have mechanical properties similar to those of bladder tissue, with fibronectin and gelatin, which improved the affinity of urothelial and bladder smooth muscle cells ^[28]. The porosity of a scaffold is primarily responsible for the infiltration of stromal cells. However, even in scaffolds with high porosity, spontaneous infiltration takes a long time. Therefore, methods have been developed in which dynamic culture increases cell infiltration of scaffolds ^[29]. Compared with static seeding techniques, agitation and centrifugation result in better infiltration as far as the stromal cells are concerned, however, when it comes to the other cell types relevant to urethral regeneration more work needs to be done ^[30]^[31].

4.3. Scaffold-Free Approaches

Cell sheet engineering is a technique widely used in regenerative medicine, including urethral reconstruction. Cells are grown in culture surfaces containing a temperature-responsive polymer, the poly-N-isopropylacrylamide (PIPAAm). At 37 °C, the PIPAAm forms a dense membrane that supports cell attachment and proliferation ^[32]. When the temperature drops below its critical temperature (32 °C), the polymer swells and becomes hydrophilic, leading to spontaneous detachment of the cell layer ^[33]. This approach allows harvesting of the cells and deposited ECM without proteolytic treatment, maintaining cell adhesion molecules and important growth factors bound to the ECM. Zhou and coworkers used a dog model to demonstrate the utility of the cell layer technology in urethral reconstruction. They created tissue constructs from ASCs, oral mucosal epithelial cells, and fibroblasts that were successfully used for structural and functional regeneration of the urethra ^[34]. Compared to conventional scaffold materials, cell sheets exhibit higher cell concentration, more uniform cell distribution, higher cell viability, and no immune system activation caused by scaffold materials. Cell sheets in clinical use today are derived from autologous cells, which reduces the risk of immune rejection, but the current cost required to produce patient-derived cell sheets severely limits their widespread use. Off-the-shelf allografts may be an option in the future; however, further research is needed to determine how to manage risks associated with immune rejection and/or transmission of infection.

4.4. Bioprinting

Bioprinting is a relatively new technology, but it already has shown great potential for producing complex cell-laden constructs that can be tailored to specific needs ^[35]. A unique advantage is that it can be used to create different cellular structures to mimic the complexity of natural tissues, which is not possible with conventional scaffold-based technology ^[36]. Using 3D printing technologies, Zhang and coworkers fabricated a structure mimicking the structural and mechanical properties of the rabbit urethra ^[37]. A 3D-printed spiral tubular scaffold served as a support for two cell-loaded hydrogel layers in the outer and inner surfaces, containing SMCs and UCs, respectively. Although the maturation of the cells was not investigated, this entry provided the first proof of concept that bioprinting is a promising approach to assembling the different layers of the urethra in predefined spatial patterns. In another study, Pi and coworkers developed a multichannel coaxial extrusion technique for printing tubular structures with multiple circumferential layers. With this technology, and using a sodium alginate and gelatin methacrylate (GelMA) blend bioink loaded with human UCs and SMCs, they printed tubular structures that mimicked urethral tissue ^[38]. Their results show that bioprinting not only allows for high structural fidelity but also that the cells retain the ability to proliferate and differentiate. These results support the use of bioprinting in urethral tissue engineering, but issues, such as biomaterial selection, fine-tuning of printing parameters, crosslinking time, and mechanical properties need to be addressed to optimize the functional performance of the constructs.

4.5. Bioreactors

Bioreactors are systems that provide a more physiologically relevant environment for cultures compared to traditional static conditions and allow for organ modeling in vitro. By regulating pH, temperature, oxygen partial pressure, cell perfusion, and external mechanical stimuli, these systems support tissue development by providing the biochemical and physical regulatory signals required for cell proliferation, differentiation, and ECM production ^[39]. Simultaneous application of biophysical and biochemical stimulation signals in the bioreactors results in synergistic responses that are expected to significantly improve the functional properties of the cells ^[40]. Wang and coworkers investigated the feasibility of dynamic mechanical stimulation to promote smooth myogenic differentiation of ASCs seeded on polyglycolic acid (PGA) ^[41]. After one week of static culture, tubular cell-PGA constructs were induced by 5-azacytidine (5-aza) and stimulated in a pulsatile flow bioreactor for five weeks. Histological examination revealed that the urethral-shaped constructs contained smooth muscle-like cells and well-oriented collagen fibers. Similarly, Yang and colleagues were able to employ the pulsed-flow conditions to achieve the formation of a fully developed multilayer UC epithelial layer within the tubular collagen scaffold ^[42]. In line with this entry, Versteegden and coworkers developed a system to mimic the urine flow stress on the human urethra, demonstrating that mechanical stimulation is critical for maintaining a tight epithelial layer ^[43]. While significant progress has been made in the design, construction, and application of bioreactors for urethral tissue engineering, most bioreactors are currently dedicated devices with low-volume output. The optimal culture conditions for different cell types on different scaffolds need to be further optimized.

4.6. Addition of Bioactive Factors

Recent studies have shown that growth factors can be incorporated into the tissue-engineered constructs to meet cell growth and maturation requirements, and also to support the development of a functional vasculature that is critical for graft survival ^[34]^[44]^[45]. For example, Loai and coworkers, when experimenting with a bladder acellular matrix scaffold coated with VEGF, achieved the formation of new blood vessels as well as urothelial and smooth muscle layers in the constructs engrafted in rats and pigs ^[46]. In an attempt to provide for a more sustained signaling, a recombinant VEGF protein containing the collagen-binding domain (CBD-VEGF) was devised, and indeed it was documented as superior to simple VEGF in terms of neovascularization in a dog model ^[47].

Before urethral regeneration can become embraced as a reliable option, there is the critical issue of stricture recurrence due to tissue fibrosis, which needs to be resolved. The TGF-β1 is believed to be the culprit, thus targeting its receptor and/or signaling pathways appears of key importance, as exemplified by targeting the canonical Wnt regulatory pathway ^[48]^[49]. In this context, Zhang and coworkers introduced the Wnt pathway inhibitor ICG-001 into electrospun scaffolds ^[50]. Urethrography results showed patent urethra in all rabbits of the ICG-001 group, in contrast to the control group where the urethral strictures and fistulas were frequent. Li and coworkers produced a tissue-engineered urethral graft using oral keratinocytes and fibroblasts transfected with TGF-β1 siRNA ^[51]. The result was a decrease in collagen deposition, effectively inhibiting fibrosis. Overall, the results of these studies indicate that targeted delivery or inhibition of growth factors in the tissue-engineered grafts is a valid approach that may translate into improved in vivo performance.

References

Santucci, R.A.; Joyce, G.F.; Wise, M. Male urethral stricture disease. J. Urol. 2007, 177, 1667–1674.
Fenton, A.S.; Morey, A.F.; Aviles, R.; Garcia, C.R. Anterior urethral strictures: Etiology and characteristics. Urology 2005, 65, 1055–1058.
Hampson, L.A.; McAninch, J.W.; Breyer, B.N. Male urethral strictures and their management. Nat. Rev. Urol. 2014, 11, 43–50.
Wong, S.S.; Aboumarzouk, O.M.; Narahari, R.; O’Riordan, A.; Pickard, R. Simple urethral dilatation, endoscopic urethrotomy, and urethroplasty for urethral stricture disease in adult men. Cochrane Database Syst. Rev. 2012, 12, CD006934.
Rashidbenam, Z.; Jasman, M.H.; Hafez, P.; Tan, G.H.; Goh, E.H.; Fam, X.I.; Ho, C.C.K.; Zainuddin, Z.M.; Rajan, R.; Nor, F.M.; et al. Overview of urethral reconstruction by tissue engineering: Current strategies, clinical status and future direction. Tissue Eng. Regen. Med. 2019, 16, 365–384.
Dublin, N.; Stewart, L.H. Oral complications after buccal mucosal graft harvest for urethroplasty. BJU Int. 2004, 94, 867–869.
Horiguchi, A. Substitution urethroplasty using oral mucosa graft for male anterior urethral stricture disease: Current topics and reviews. Int. J. Urol. 2017, 24, 493–503.
Chan, Y.Y.; Bury, M.I.; Yura, E.M.; Hofer, M.D.; Cheng, E.Y.; Sharma, A.K. The current state of tissue engineering in the management of hypospadias. Nat. Rev. Urol. 2020, 17, 162–175.
Xue, J.D.; Gao, J.; Fu, Q.; Feng, C.; Xie, H. Seeding cell approach for tissue-engineered urethral reconstruction in animal study: A systematic review and meta-analysis. Exp. Biol. Med. 2016, 241, 1416–1428.
Abbas, T.O.; Mahdi, E.; Hasan, A.; AlAnsari, A.; Pennisi, C.P. Current status of tissue engineering in the management of severe hypospadias. Front. Pediatr. 2018, 5, 283.
De Filippo, R.E.; Yoo, J.J.; Atala, A. Urethral replacement using cell seeded tubularized collagen matrices. J. Urol. 2002, 168, 1789–1793.
Osman, N.I.; Hillary, C.; Bullock, A.J.; MacNeil, S.; Chapple, C.R. Tissue engineered buccal mucosa for urethroplasty: Progress and future directions. Adv. Drug Deliv. Rev. 2015, 82, 69–76.
Palminteri, E.; Berdondini, E.; Fusco, F.; De Nunzio, C.; Salonia, A. Long-term results of small intestinal submucosa graft in bulbar urethral reconstruction. Urology 2012, 79, 695–701.
Versteegden, L.R.; De Jonge, P.K.; IntHout, J.; Van Kuppevelt, T.H.; Oosterwijk, E.; Feitz, W.F.; De Vries, R.B.M.; Daamen, W.F. Tissue engineering of the urethra: A systematic review and meta-analysis of preclinical and clinical studies. Eur. Urol. 2017, 72, 594–606.
De Kemp, V.; De Graaf, P.; Fledderus, J.O.; Ruud Bosch, J.L.H.; De Kort, L.M. Tissue engineering for human urethral reconstruction: Systematic review of recent literature. PLoS ONE 2015, 10, e0118653.
Mangera, A.; Chapple, C.R. Tissue engineering in urethral reconstruction—An update. Asian J Androl 2013, 15, 89–92.
Abbas, T.O.; Yalcin, H.C.; Pennisi, C.P. From acellular matrices to smart polymers: Degradable scaffolds that are transforming the shape of urethral tissue engineering. Int. J. Mol. Sci. 2019, 20, 1763.
Hickling, D.R.; Sun, T.T.; Wu, X.R. Anatomy and physiology of the urinary tract: Relation to host defense and microbial infection. Microbiol. Spectr. 2017, 3, 1–25.
Wessells, H.; Lue, T.F.; McAninch, J.W. Penile length in the flaccid and erect states: Guidelines for penile augmentation. J. Urol. 1996, 156, 995–997.
Tiemessen, D.; de Jonge, P.; Daamen, W.; Feitz, W.; Geutjes, P.; Oosterwijk, E. The effect of a cyclic uniaxial strain on urinary bladder cells. World J. Urol. 2017, 35, 1531–1539.
Horiguchi, A.; Ojima, K.; Shinchi, M.; Mayumi, Y.; Kushibiki, T.; Katoh, S.; Takeda, M.; Iwasaki, M.; Yoshioka, H.; Abraham, S.J.; et al. In Vitro Culture Expansion and Characterization of Buccal Mucosal Epithelial Cells for Tissue Engineering Applications in Urethral Stricture After Transportation Using a Thermoreversible Gelation Polymer. Biopreserv. Biobank 2022, 20, 97–103.
Bhardwaj, N.; Kundu, S.C. Electrospinning: A fascinating fiber fabrication technique. Biotechnol. Adv. 2010, 28, 325–347.
Zamani, M.; Shakhssalim, N.; Ramakrishna, S.; Naji, M. Electrospinning: Application and prospects for urologic tissue engineering. Front Bioeng. Biotechnol. 2020, 8, 579925.
Wang, D.J.; Li, M.Y.; Huang, W.T.; Lu, M.H.; Hu, C.; Li, K.; Qiu, J.Q.; Gao, X. Repair of urethral defects with polylactid acid fibrous membrane seeded with adipose-derived stem cells in a rabbit model. Connect Tissue Res. 2015, 56, 434–439.
Xie, M.; Song, L.; Wang, J.; Fan, S.; Zhang, Y.; Xu, Y. Evaluation of stretched electrospun silk fibroin matrices seeded with urothelial cells for urethra reconstruction. J. Surg. Res. 2013, 184, 774–781.
Simsek, A.; Bullock, A.J.; Roman, S.; Chapple, C.R.; Macneil, S. Developing improved tissue-engineered buccal mucosa grafts for urethral reconstruction. Can. Urol. Assoc. J. 2018, 12, E234–E242.
Sievert, K.D.; Daum, L.; Maurer, S.; Toomey, P.; Vaegler, M.; Aufderklamm, S.; Amend, B. Urethroplasty performed with an autologous urothelium-vegetated collagen fleece to treat urethral stricture in the minipig model. World J. Urol. 2020, 38, 2123–2131.
Uchida, N.; Sivaraman, S.; Amoroso, N.J.; Wagner, W.R.; Nishiguchi, A.; Matsusaki, M.; Akashi, M.; Nagatomi, J. Nanometer-sized extracellular matrix coating on polymer-based scaffold for tissue engineering applications. J. Biomed Mater. Res. A 2016, 104, 94–103.
Gnecchi, M.; Danieli, P.; Malpasso, G.; Ciuffreda, M.C. Paracrine mechanisms of mesenchymal stem cells in tissue repair. Methods Mol. Biol. 2016, 1416, 123–146.
Lv, X.G.; Feng, C.; Fu, Q.; Xie, H.; Wang, Y.; Huang, J.W.; Xie, M.K.; Atala, A.; Xu, Y.M.; Zhao, W.X. Comparative study of different seeding methods based on a multilayer SIS scaffold: Which is the optimal procedure for urethral tissue engineering? J. Biomed Mater. Res. B Appl. Biomater. 2016, 104, 1098–1108.
Melke, J.; Zhao, F.; Ito, K.; Hofmann, S. Orbital seeding of mesenchymal stromal cells increases osteogenic differentiation and bone-like tissue formation. J. Orthop. Res. 2020, 38, 1228–1237.
Akiyama, Y.; Kikuchi, A.; Yamato, M.; Okano, T. Ultrathin poly (N-isopropylacrylamide) grafted layer on polystyrene surfaces for cell adhesion/detachment control. Langmuir 2004, 20, 5506–5511.
Masuda, S.; Shimizu, T. Three-dimensional cardiac tissue fabrication based on cell sheet technology. Adv. Drug Deliv. Rev. 2016, 96, 103–109.
Zhou, S.; Yang, R.; Zou, Q.; Zhang, K.; Yin, T.; Zhao, W.; Shapter, J.G.; Gao, G.; Fu, Q. Fabrication of tissue-engineered bionic urethra using cell sheet technology and labeling by ultrasmall superparamagnetic iron oxide for full-thickness urethral reconstruction. Theranostics 2017, 7, 2509–2523.
Lal, H.; Patralekh, M.K. 3D printing and its applications in orthopaedic trauma: A technological marvel. J. Clin. Orthop. Trauma 2018, 9, 260–268.
Xu, T.; Zhao, W.; Zhu, J.M.; Albanna, M.Z.; Yoo, J.J.; Atala, A. Complex heterogeneous tissue constructs containing multiple cell types prepared by inkjet printing technology. Biomaterials 2013, 34, 130–139.
Zhang, K.; Fu, Q.; Yoo, J.; Chen, X.; Chandra, P.; Mo, X.; Song, L.; Atala, A.; Zhao, W. 3D bioprinting of urethra with PCL/PLCL blend and dual autologous cells in fibrin hydrogel: An in vitro evaluation of biomimetic mechanical property and cell growth environment. Acta Biomater. 2017, 50, 154–164.
Pi, Q.; Maharjan, S.; Yan, X.; Liu, X.; Singh, B.; van Genderen, A.M.; Robledo-padilla, F.; Parra-Saldivar, R.; Hu, N.; Zhang, Y.S.; et al. Digitally tunable microfluidic bioprinting of multilayered cannular tissues. Adv. Mater. 2018, 30, e1706913.
Davis, N.F.; Mooney, R.; Piterina, A.V.; Callanan, A.; McGuire, B.B.; Flood, H.D.; McGloughlin, T.M. Construction and evaluation of urinary bladder bioreactor for urologic tissue-engineering purposes. Urology 2011, 78, 954–960.
Bakhshandeh, B.; Ranjbar, N.; Abbasi, A.; Amiri, E.; Abedi, A.; Mehrabi, M.R.; Dehghani, Z.; Pennisi, C.P. Recent progress in the manipulation of biochemical and biophysical cues for engineering functional tissues. Bioeng. Transl. Med. 2022, e10383.
Wang, Y.; Fu, Q.; Zhao, R.Y.; Deng, C.L. Muscular tubes of urethra engineered from adipose-derived stem cells and polyglycolic acid mesh in a bioreactor. Biotechnol. Lett. 2014, 36, 1909–1916.
Yang, P.J.; Pham, J.; Choo, J.; Hu, D.L. Duration of urination does not change with body size. Proc. Natl. Acad. Sci. USA 2014, 111, 11932–11937.
Versteegden, L.R.; Van Kampen, K.A.; Janke, H.P.; Tiemessen, D.M.; Hoogenkamp, H.R.; Hafmans, T.G.; Roozen, E.A.; Lomme, R.M.; Van Goor, H.; Daamen, W.F.; et al. Tubular collagen scaffolds with radial elasticity for hollow organ regeneration. Acta Biomater. 2017, 52, 1–8.
Guan, Y.; Ou, L.; Hu, G.; Wang, H.; Xu, Y.; Chen, J.; Zhang, J.; Yu, Y.; Kong, D. Tissue engineering of urethra using human vascular endothelial growth factor gene-modified bladder urothelial cells. Artif. Organs 2008, 32, 91–99.
Tsao, C.J.; Pandolfi, L.; Wang, X.; Minardi, S.; Lupo, C.; Evangelopoulos, M.; Hendrickson, T.; Shi, A.; Storci, G.; Taraballi, F.; et al. Electrospun patch functionalized with nanoparticles allows for spatiotemporal release of VEGF and PDGF-BB promoting in vivo neovascularization. ACS Appl. Mater. Interfaces 2018, 10, 44344–44353.
Loai, Y.; Yeger, H.; Coz, C.; Antoon, R.; Islam, S.S.; Moore, K.; Farhat, W.A. Bladder tissue engineering: Tissue regeneration and neovascularization of HA-VEGF-incorporated bladder acellular constructs in mouse and porcine animal models. J. Biomed Mater. Res. A 2010, 94, 1205–1215.
Jia, W.; Tang, H.; Wu, J.; Hou, X.; Chen, B.; Chen, W.; Zhao, Y.; Shi, C.; Zhou, F.; Yu, W.; et al. Urethral tissue regeneration using collagen scaffold modified with collagen binding VEGF in a beagle model. Biomaterials 2015, 69, 45–55.
Cheng, J.H.; She, H.; Han, Y.P.; Wang, J.; Xiong, S.; Asahina, K.; Tsukamoto, H. Wnt antagonism inhibits hepatic stellate cell activation and liver fibrosis. Am. J. Physiol. Gastrointest. Liver Physiol. 2008, 294, G39–G49.
Conidi, A.; Van den Berghe, V.; Huylebroeck, D. Aptamers and Their Potential to Selectively Target Aspects of EGF, Wnt/β-Catenin and TGFβ–Smad Family Signaling. Int. J. Mol. Sci. 2013, 14, 6690–6719.
Zhang, K.; Guo, X.; Zhao, W.; Niu, G.; Mo, X.; Fu, Q. Application of Wnt pathway inhibitor delivering scaffold for inhibiting fibrosis in urethra strictures: In vitro and in vivo study. Int. J. Mol. Sci. 2015, 16, 27659–27676.
Li, C.; Xu, Y.M.; Liu, Z.S.; Li, H.B. Urethral reconstruction with tissue engineering and RNA interference techniques in rabbits. Urology 2013, 81, 1075–1080.

© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.

Upload a video for this entry

Information

Subjects: Cell & Tissue Engineering

Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :

Zongzhe Xuan

Vladimir Zachar

Cristian Pablo Pennisi

View Times: 972

Update Date: 25 Nov 2022

Table of Contents

Video Upload Options

Confirm