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Joshua R. Mauney – 1st expert on this subject based on the ideXlab platform
the use of bi layer silk fibroin scaffolds and small intestinal submucosa matrices to support Bladder Tissue regeneration in a rat model of spinal cord injuryBiomaterials, 2014Co-Authors: Yeun Goo Chung, Carlos R. Estrada, Roslyn M. Adam, Debra Franck, David L Kaplan, Khalid Algarrahi, Duong Tu, Joshua R. MauneyAbstract:
Adverse side-effects associated with enterocystoplasty for neurogenic Bladder reconstruction have spawned the need for the development of alternative graft substitutes. Bi-layer silk fibroin (SF) scaffolds and small intestinal submucosa (SIS) matrices were investigated for their ability to support Bladder Tissue regeneration and function in a rat model of spinal cord injury (SCI). Bladder augmentation was performed with each scaffold configuration in SCI animals for 10 wk of implantation and compared to non-augmented control groups (normal and SCI alone). Animals subjected to SCI alone exhibited a 72% survival rate (13/18) while SCI rats receiving SIS and bi-layer SF scaffolds displayed respective survival rates of 83% (10/12) and 75% (9/12) over the course of the study period. Histological (Masson’s trichrome analysis) and immunohistochemical (IHC) evaluations demonstrated both implant groups supported de novo formation of smooth muscle layers with contractile protein expression [α-smooth muscle actin (α-SMA) and SM22α] as well as maturation of multi-layer urothelia expressing cytokeratin (CK) and uroplakin 3A proteins. Histomorphometric analysis revealed bi-layer SF and SIS scaffolds respectively reconstituted 64% and 56% of the level of α-SMA+ smooth muscle bundles present in SCI-alone controls, while similar degrees of CK+ urothelium across all experimental groups were detected. Parallel evaluations showed similar degrees of vascular area and synaptophysin+ boutons in all regenerated Tissues compared to SCI-alone controls. In addition, improvements in certain urodynamic parameters in SCI animals, such as decreased peak intravesical pressure, following implantation with both matrix configurations were also observed. The data presented in this study detail the ability of acellular SIS and bi-layer SF scaffolds to support formation of innervated, vascularized smooth muscle and urothelial Tissues in a neurogenic Bladder model.
evaluation of silk biomaterials in combination with extracellular matrix coatings for Bladder Tissue engineering with primary and pluripotent cellsPLOS ONE, 2013Co-Authors: Debra Franck, Carlos R. Estrada, Joshua R. Mauney, Roslyn M. Adam, David L Kaplan, Yeun Goo ChungAbstract:
Silk-based biomaterials in combination with extracellular matrix (ECM) coatings were assessed as templates for cell-seeded Bladder Tissue engineering approaches. Two structurally diverse groups of silk scaffolds were produced by a gel spinning process and consisted of either smooth, compact multi-laminates (Group 1) or rough, porous lamellar-like sheets (Group 2). Scaffolds alone or coated with collagen types I or IV or fibronectin were assessed independently for their ability to support attachment, proliferation, and differentiation of primary cell lines including human Bladder smooth muscle cells (SMC) and urothelial cells as well as pluripotent cell populations, such as murine embryonic stem cells (ESC) and induced pluripotent stem (iPS) cells. AlamarBlue evaluations revealed that fibronectin-coated Group 2 scaffolds promoted the highest degree of primary SMC and urothelial cell attachment in comparison to uncoated Group 2 controls and all Group 1 scaffold variants. Real time RT-PCR and immunohistochemical (IHC) analyses demonstrated that both fibronectin-coated silk groups were permissive for SMC contractile differentiation as determined by significant upregulation of α-actin and SM22α mRNA and protein expression levels following TGFβ1 stimulation. Prominent expression of epithelial differentiation markers, cytokeratins, was observed in urothelial cells cultured on both control and fibronectin-coated groups following IHC analysis. Evaluation of silk matrices for ESC and iPS cell attachment by alamarBlue showed that fibronectin-coated Group 2 scaffolds promoted the highest levels in comparison to all other scaffold formulations. In addition, real time RT-PCR and IHC analyses showed that fibronectin-coated Group 2 scaffolds facilitated ESC and iPS cell differentiation toward both urothelial and smooth muscle lineages in response to all trans retinoic acid as assessed by induction of uroplakin and contractile gene and protein expression. These results demonstrate that silk scaffolds support primary and pluripotent cell responses pertinent to Bladder Tissue engineering and that scaffold morphology and fibronectin coatings influence these processes.
Silk as a Novel Biomaterial in Bladder Tissue EngineeringJournal of Pediatric Urology, 2010Co-Authors: Glenn M. Cannon, Joshua R. Mauney, Edward M. Gong, Richard N. Yu, Roslyn M. Adam, Carlos R. EstradaAbstract:
Purpose The ideal biomaterial for Bladder Tissue engineering remains elusive. Silk has been utilized in vascular and orthopedic applications, and possesses physical and biological properties well suited for urologic applications. We hypothesize that silk scaffolds can be utilized for Bladder Tissue engineering. Methods Silk fibroin solution from Bombyx mori silkworm cocoons were woven into patches using gel spinning. Bladder augmentations were performed in 25 CD-1 female mice with non-cell seeded silk, PGA, or SIS patches (0.5 cm2). Sham procedures of cystotomy only were performed. Postoperative assessment at 1, 3, 6, and 10 weeks included: 1) voiding stain on paper (VSOP) testing for qualitative and quantitative assessment of voiding, 2) ultrasound to assess Bladder and renal appearance, 3) pathological analysis including Masson trichrome and immunofluorescence of smooth muscle (alpha actin) and urothelial (uroplakin IIIa) markers, and 4) Urodynamics (Bladder capacity, voided volume, urinary flow rate, and Bladder compliance). Statistical analysis was performed by ANOVA with post-hoc Bonferroni testing. Results VSOP revealed normalization of voiding pattern in silk-augmented mice at 1 week that persisted to 10 weeks. Renal and Bladder ultrasound demonstrated normal kidneys and gradual Bladder remodeling over 10 weeks. Histological analysis of silk-augmented Bladders revealed complete organized Bladder Tissue formation without fibrosis around the silk scaffolds by 10 weeks. The new Tissue stained robustly for alpha actin (Figure 1) and uroplakin IIIa (Figure 2). 10 weeks after augmentation, mean capacity of silk-augmented Bladders was 207 (mcL) v. 51 for controls (p Conclusions Unseeded silk scaffolds promote formation of organized and functional Bladder Tissue in mice. In addition, silk produces superior compliance compared to conventional biomaterials. This represents a new option for urologic Tissue engineering applications.
Walid A. Farhat – 2nd expert on this subject based on the ideXlab platform
Review of clinical experience on biomaterials and Tissue engineering of urinary BladderWorld Journal of Urology, 2019Co-Authors: Michael E. Chua, Walid A. Farhat, Jessica M. Ming, Kurt A. MccammonAbstract:
PurposeIn recent pre-clinical studies, biomaterials and Bladder Tissue engineering have shown promising outcomes when addressing the need for Bladder Tissue replacement. To date, multiple clinical experiences have been reported. Herein, we aim to review and summarize the reported clinical experience of biomaterial usage and Tissue engineering of the urinary Bladder.MethodsA systematic literature search was performed on Feb 2019 to identify clinical reports on biomaterials for urinary Bladder replacement or augmentation and clinical experiences with Bladder Tissue engineering. We identified and reviewed human studies using biomaterials and Tissue-engineered Bladder as Bladder substitutes or augmentation implants. The studies were then summarized for each respective procedure indication, technique, follow-up period, outcome, and important findings of the studies.ResultsAn extensive literature search identified 25 studies of case reports and case series with a cumulative clinical experience of 222 patients. Various biomaterials and Tissue-engineered Bladder were used, including plastic/polyethylene mold, preserved dog Bladder, gelatine sponge, Japanese paper with Nobecutane, lypholized human dura, bovine pericardium, amniotic membrane, small intestinal mucosa, and Bladder Tissue engineering with autologous cell-seeded biodegradable scaffolds. However, overall clinical experiences including the outcomes and safety reports were not satisfactory enough to replace enterocystoplasty.ConclusionTo date, several clinical experiences of biomaterials and Tissue-engineered Bladder have been reported; however, various studies have reported non-satisfactory outcomes. Further technological advancements and a better understanding is needed to advance Bladder Tissue engineering as a future promising management option for patients requiring Bladder drainage.
review of clinical experience on biomaterials and Tissue engineering of urinary BladderWorld Journal of Urology, 2019Co-Authors: Michael E. Chua, Walid A. Farhat, Jessica M. Ming, Kurt A. MccammonAbstract:
In recent pre-clinical studies, biomaterials and Bladder Tissue engineering have shown promising outcomes when addressing the need for Bladder Tissue replacement. To date, multiple clinical experiences have been reported. Herein, we aim to review and summarize the reported clinical experience of biomaterial usage and Tissue engineering of the urinary Bladder.
Does mechanical stimulation have any role in urinary Bladder Tissue engineering?World Journal of Urology, 2008Co-Authors: Walid A. Farhat, Herman YegerAbstract:
Introduction Tissue engineering of the urinary Bladder currently relies on biocompatible scaffolds that deliver biological and physical functionality with negligible risks of immunogenic or tumorigenic potential. Recent research suggests that autologous cells that are propagated in culture and seeded on scaffolds prior to implantation improve clinical outcomes. For example, normal urinary Bladder development in utero requires regular filling and emptying, and current research suggests that Bladders constructed in vitro may also benefit from regular mechanical stimulation. Such stimulation appears to induce favorable cellular changes, proliferation, and production of structurally suitable extracellular matrix (ECM) components essential for the normal function of hollow dynamic organs. Materials and methods To mimic in vivo urinary Bladder dynamics, Tissue bioreactors that imitate the filling and emptying of a normal Bladder have been devised. A “urinary Bladder Tissue bioreactor” that is able to recapitulate these dynamics while providing a cellular environment that facilitates cell–cell and cell–matrix interactions normally seen in-vivo may be necessary to successfully engineer Bladder Tissue. Conclusions The validation of a urinary Bladder Tissue bioreactor that permits careful control of physiological conditions will generate a broad interest from researchers interested in urinary Bladder physiology and Tissue engineering.
Jacques Corcos – 3rd expert on this subject based on the ideXlab platform
Bladder Tissue engineering a literature reviewAdvanced Drug Delivery Reviews, 2015Co-Authors: Shachar Aharony, Oleg Loutochin, Jacques CorcosAbstract:
Abstract Purpose of review In Bladder cancer and neuro-Bladder, reconstruction of the Bladder requires bowel segment grafting for augmentation cystoplasty or neo-Bladder creation. However, even if currently considered as the gold standard, it is associated with potentially severe short- and long-term adverse effects. Thus, Bladder Tissue engineering is a promising approach to Bladder reconstruction. Recent findings In the last few years, progress has been made with the development of new biomaterials for Bladder Tissue replacement and in deciphering the role of stem cells as well as their contribution to Bladder scaffold integration and Tissue regeneration. Summary This review of recently published articles allows us to forecast the characteristics of efficient and safe Bladder biomaterials. However, several factors, such as native Bladder traits, the specific involvement of urine, and Bladder Tissue replacement indications, have to be assessed with caution before including Bladder Tissue engineering in clinical trials. Many authors agree that these challenging techniques could deliver significant benefits with clinical application, reducing morbidity and global long-term costs.
Tissue engineering of rat Bladder using marrow derived mesenchymal stem cells and Bladder acellular matrixPLOS ONE, 2014Co-Authors: Daniel L Coutu, Wally Mahfouz, Oleg Loutochin, Jacques Galipeau, Jacques CorcosAbstract:
Bladder replacement or augmentation is required in congenital malformations or following trauma or cancer. The current surgical solution involves enterocystoplasty but is associated with high complication rates. Strategies for Bladder Tissue engineering are thus actively sought to address this unmet clinical need. Because of the poor efficacy of synthetic polymers, the use of Bladder acellular matrix (BAM) has been proposed. Indeed when cellular components are removed from xenogenic or allogeneic Bladders, the extracellular matrix scaffold thus obtained can be used alone or in combination with stem cells. In this study, we propose the use of BAM seeded with marrow-derived mesenchymal stem cells (MSCs) for Bladder Tissue engineering. We optimized a protocol for decellularization of Bladder Tissue from different species including rat, rabbit and swine. We demonstrate the use of non-ionic detergents followed by nuclease digestion results in efficient decellularization while preserving the extracellular matrix. When MSCs were seeded on acellular matrix scaffold, they remained viable and proliferative while adopting a cellular phenotype consistent with their microenvironment. Upon transplantation in rats after partial cystectomy, MSC-seeded BAM proved superior to unseeded BAM with animals recovering nearly 100% normal Bladder capacity for up to six months. Histological analyses also demonstrated increased muscle regeneration.
Fundamentals of Bladder Tissue engineeringAfrican Journal of Urology, 2013Co-Authors: Wally Mahfouz, Jacques Corcos, Salah Elsalmy, A.s. FayedAbstract:
Abstract A wide range of injuries could affect the Bladder and lead to eventual loss of its integrity, with the need for replacement or repair. Augmentation ileocystoplasty is considered till now the gold standard option for Bladder replacement, despite its associated complications. Bladder Tissue engineering appears as an appealing alternative through development of biological substitutes, which could restore structural and functional aspects of damaged Tissues and organs. Tissue engineering relies upon three essential pillars; the scaffold, the cells seeded on scaffolds and lastly the environmental conditions, including growth factors, cytokines and extracellular matrix (ECM) which promote angiogenesis and neurogenesis of the regenerated organs. The choice of the scaffold and the type of cells is a crucial and fundamental step in regenerative medicine. In this review article, we demonstrated these three crucial factors of Bladder Tissue engineering, with the pros and cons of each scaffold type and cell type used.