Cell-Seeded Extracellular Matrices for Bladder Reconstruction: An ex vivo Comparative Study of their Biomechanical Properties

Davis, Niall F.; Mooney, Rory; Piterina, Anna V.; Callanan, Anthony; Flood, Hugh D.; McGloughlin, Timothy M.

doi:10.5301/ijao.5000194

Cited by 8 publications

(8 citation statements)

References 27 publications

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“…Several research groups demonstrated that urological tissue bioreactors could improve the proliferative activity of SMCs and UCs on scaffolds prior to in vivo implantation [29,30,31]. In the present study, compressed collagen type I tubes were obtained by using a molding and compression technique demonstrated (Supplementary Figure 1A).…”

Section: Discussionmentioning

confidence: 79%

Tubular Compressed Collagen Scaffolds for Ureteral Tissue Engineering in a Flow Bioreactor System

Vardar

Engelhardt

Larsson

et al. 2015

Tissue Engineering Part A

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Ureteral replacement by tissue engineering might become necessary following tissue loss after excessive ureteral trauma, after retroperitoneal cancer, or even after failed reconstructive surgery. This need has driven innovation in the design of novel scaffolds and specific cell culture techniques for urinary tract reconstruction. In this study, compressed tubular collagen scaffolds were evaluated, addressing the physical and biological characterization of acellular and cellular collagen tubes in a new flow bioreactor system, imitating the physiological pressure, peristalsis, and flow conditions of the human ureter. Collagen tubes, containing primary human smooth muscle and urothelial cells, were evaluated regarding their change in gene and protein expression under dynamic culture conditions. A maximum intraluminal pressure of 22.43 ± 0.2 cm H2O was observed in acellular tubes, resulting in a mean wall shear stress of 4 dynes/cm(2) in the tubular constructs. Dynamic conditions directed the differentiation of both cell types into their mature forms. This was confirmed by their gene expression of smooth muscle alpha-actin, smoothelin, collagen type I and III, elastin, laminin type 1 and 5, cytokeratin 8, and uroplakin 2. In addition, smooth muscle cell alignment predominantly perpendicular to the flow direction was observed, comparable to the cell orientation in native ureteral tissue. These results revealed that coculturing human smooth muscle and urothelial cells in compressed collagen tubes under human ureteral flow-mimicking conditions could lead to cell-engineered biomaterials that might ultimately be translated into clinical applications.

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Section: Discussionmentioning

confidence: 79%

Tubular Compressed Collagen Scaffolds for Ureteral Tissue Engineering in a Flow Bioreactor System

Vardar

Engelhardt

Larsson

et al. 2015

Tissue Engineering Part A

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“…8,11 Their harvesting sites differ; however both can be utilised as interposition grafts within the urinary tract as they support ingrowth of native tissue, proliferation and differentiation of multilayered urothelial and smooth cells layers while maintaining a robust connective tissue layer to provide mechanical support to the urinary tract. 12 SIS is harvested from porcine small bowel and contains significant amounts of collagen type I with lesser amounts of collagen types III, IV, V and VI. 4 UBM is harvested from the porcine urinary bladder and contains an intact basement membrane layer with large quantities of collagen type VII.…”

Section: Urological Ecmsmentioning

confidence: 99%

“…Viability/cytotoxicity fluorescence assays with three-dimensional confocal microscopy illustrating viable and proliferating urothelial (UCs) and smooth muscle (SMCs) cell lines on urinary bladder matrix (UBM) after 6, 10, and 14 days of dynamic culture (A, B, and C, respectively). 12 The cell-seeded scaffolds are stained with calcein and ethidiumhomodimer-1 (Ethd-1; Molecular Probes, Eugene, OR, USA). Calcein is actively converted to calcein-AM in viable cells, which appear green under a fluorescence microscope.…”

Section: Uretermentioning

confidence: 99%

“…Ethd-1 accumulates in dead cells and on the ECM scaffold, which appears red. 12 composite scaffold was utilised for augmentation cystoplasty in patients with spina bifida (n ¼ 10). 42 There was no improvement in bladder capacity on urodynamics after 1-year or 3-years and serious adverse events occurred in 4 patients with 5 patients requiring re-operation in the form of a conventional ileocystoplasty.…”

Section: Uretermentioning

confidence: 99%

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Tissue engineered extracellular matrices (ECMs) in urology: Evolution and future directions

et al. 2018

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Autologous gastrointestinal tissue has remained the gold-standard reconstructive biomaterial in urology for >100 years. Mucus-secreting epithelium is associated with lifelong metabolic and neuromechanical complications when implanted into the urinary tract. Therefore, the availability of biocompatible tissue-engineered biomaterials such as extracellular matrix (ECM) scaffolds may provide an attractive alternative for urologists. ECMs are decellularised, biodegradable membranes that have shown promise for repairing defective urinary tract segments in vitro and in vivo by inducing a host-derived tissue remodelling response after implantation. In urology, porcine small intestinal submucosa (SIS) and porcine urinary bladder matrix (UBM) are commonly selected as ECMs for tissue regeneration. Both ECMs support ingrowth of native tissue and differentiation of multi-layered urothelial and smooth muscle cells layers while providing mechanical support in vivo. In their native acellular state, ECM scaffolds can repair small urinary tract defects. Larger urinary tract segments can be repaired when ECMs are manipulated by seeding them with various cell types prior to in vivo implantation. In the present review, we evaluate and summarise the clinical potential of tissue engineered ECMs in reconstructive urology with emphasis on their long-term outcomes in urological clinical trials.

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“…There is a particular need to ensure mechanical viability of biological scaffolds [67] because directly after implantation they lack the full complement of cells which typically reside within native organs. These cells contribute significantly to the organ's mechanical properties, particularly smooth muscle cells (SMCs) which are capable of active force generation.…”

Section: Te Organ Biomechanicsmentioning

confidence: 99%

The Use of Mathematical Modelling for Improving the Tissue Engineering of Organs and Stem Cell Therapy

Lemon¹,

Sjöqvist²,

Lim³

et al. 2016

CSCR

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Regenerative medicine is a multidisciplinary field where continued progress relies on the incorporation of a diverse set of technologies from a wide range of disciplines within medicine, science and engineering. This review describes how one such technique, mathematical modelling, can be utilised to improve the tissue engineering of organs and stem cell therapy. Several case studies, taken from research carried out by our group, ACTREM, demonstrate the utility of mechanistic mathematical models to help aid the design and optimisation of protocols in regenerative medicine.

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Cell-Seeded Extracellular Matrices for Bladder Reconstruction: An ex vivo Comparative Study of their Biomechanical Properties

Abstract: Dynamically cultured cell-seeded ECMs are biomechanically superior to ileal tissue for bladder replacement purposes. Additional comparative in vivo studies will be necessary before their role as a reliable alternative is clearly established.

Cited by 8 publications

References 27 publications

Tubular Compressed Collagen Scaffolds for Ureteral Tissue Engineering in a Flow Bioreactor System

Tubular Compressed Collagen Scaffolds for Ureteral Tissue Engineering in a Flow Bioreactor System

Tissue engineered extracellular matrices (ECMs) in urology: Evolution and future directions

The Use of Mathematical Modelling for Improving the Tissue Engineering of Organs and Stem Cell Therapy

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