title: New insights into the effects of biomaterial chemistry and topography on the morphology of kidney epithelial cells.
abstract: Increasing incidence of renal pathology in the western world calls for innovative research for the development of cell-based therapies such as a bioartificial kidney (BAK) device. To fulfil the multitude of kidney functions, the core component of the BAK is a living membrane consisting of a tight kidney cell monolayer with preserved functional organic ion transporters cultured on a polymeric membrane surface. This membrane, on one side, is in contact with blood and therefore should have excellent blood compatibility, whereas the other side should facilitate functional monolayer formation. This work investigated the effect of membrane chemistry and surface topography on kidney epithelial cells to improve the formation of a functional monolayer. To achieve this, microtopographies were fabricated with high resolution and reproducibility on polystyrene films and on polyethersulfone-polyvinyl pyrrolidone (PES-PVP) porous membranes. A conditionally immortalized proximal tubule epithelial cell line (ciPTEC) was cultured on both, and subsequently, the cell morphology and monolayer formation were assessed. Our results showed that L-dopamine coating of the PES-PVP was sufficient to support ciPTEC monolayer formation. The polystyrene topographies with large features were able to align the cells in various patterns without significantly disruption of monolayer formation; however, the PES-PVP topographies with large features disrupted the monolayer. In contrast, the PES-PVP membranes with small features and with large spacing supported well the ciPTEC monolayer formation. In addition, the topographical PES-PVP membranes were compatible as a substrate membrane to measure organic cation transporter activity in Transwell® systems. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Department of Biomaterials Science and Technology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.|Department of Cell Biology inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, University of Maastricht, Maastricht, The Netherlands.
authors.forename: Frits
authors.initials: F
authors.lastname: Hulshof
authors.affiliation: Department of Pediatric Nephrology, Radboudumc, Nijmegen, The Netherlands.|Department of Physiology, Radboudumc, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.|Department of Pharmacology and Toxicology, Radboudumc, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: Carolien
authors.initials: C
authors.lastname: Schophuizen
authors.affiliation: Department of Pharmacology and Toxicology, Radboudumc, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.|Department of Complex Tissue Regeneration, MERLN Institute for Technology-Inspired Regenerative Medicine, University of Maastricht, Maastricht, The Netherlands.
authors.forename: Milos
authors.initials: M
authors.lastname: Mihajlovic
authors.affiliation: Department of Complex Tissue Regeneration, MERLN Institute for Technology-Inspired Regenerative Medicine, University of Maastricht, Maastricht, The Netherlands.
authors.forename: Clemens
authors.initials: C
authors.lastname: van Blitterswijk
authors.affiliation: Department of Pharmacology and Toxicology, Radboudumc, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.|Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands.
authors.forename: Rosalinde
authors.initials: R
authors.lastname: Masereeuw
authors.affiliation: Department of Cell Biology inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, University of Maastricht, Maastricht, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: de Boer
authors.affiliation: Department of Biomaterials Science and Technology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Stamatialis
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D003404:Creatinine / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D006801:Humans; D007668:Kidney / Q000166:cytology*; D008567:Membranes, Artificial; D011108:Polymers / Q000494:pharmacology; D016062:Porosity; D011205:Povidone / Q000494:pharmacology; D013450:Sulfones / Q000494:pharmacology
chemical_list: D001672:Biocompatible Materials; D008567:Membranes, Artificial; D011108:Polymers; D013450:Sulfones; C022840:polyether sulfone; D003404:Creatinine; D011205:Povidone
keywords: bioartificial kidney; biomaterial chemistry; cell morphology and function; kidney epithelial cells; membrane; surface topography