title: Tubular Compressed Collagen Scaffolds for Ureteral Tissue Engineering in a Flow Bioreactor System.
abstract: 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.
authors.affiliation: Institute of Bioengineering , School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland .
authors.forename: Elif
authors.initials: E
authors.lastname: Vardar
authors.affiliation: Institute of Bioengineering , School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland .
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Engelhardt
authors.affiliation: Institute of Bioengineering , School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland .
authors.forename: Hans M
authors.initials: HM
authors.lastname: Larsson
authors.affiliation: Institute of Bioengineering , School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland .
authors.forename: Elodie
authors.initials: E
authors.lastname: Mouloungui
authors.affiliation: Institute of Bioengineering , School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland .
authors.forename: Kalitha
authors.initials: K
authors.lastname: Pinnagoda
authors.affiliation: Institute of Bioengineering , School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland .
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Hubbell
authors.affiliation: Institute of Bioengineering , School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland .
authors.forename: Peter
authors.initials: P
authors.lastname: Frey
mesh_terms: D000818:Animals; D019149:Bioreactors; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques; D003094:Collagen / Q000494:pharmacology*; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D055595:Mechanical Phenomena; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D012212:Rheology / Q000187:drug effects; D023822:Tissue Engineering / Q000295:instrumentation* / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*; D014513:Ureter / Q000166:cytology / Q000502:physiology*
chemical_list: D003094:Collagen