Development of a novel 3D culture system for screening features of a complex implantable device for CNS repair

Donoghue, P. S., Sun, T., Gadegaard, N. , Riehle, M. O. and Barnett, S. C. (2014) Development of a novel 3D culture system for screening features of a complex implantable device for CNS repair. Molecular Pharmaceutics, 11(7), pp. 2143-2150. (doi: 10.1021/mp400526n) (PMID:24279373) (PMCID:PMC4087043)

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Tubular scaffolds which incorporate a variety of micro- and nanotopographies have a wide application potential in tissue engineering especially for the repair of spinal cord injury (SCI). We aim to produce metabolically active differentiated tissues within such tubes, as it is crucially important to evaluate the biological performance of the three-dimensional (3D) scaffold and optimize the bioprocesses for tissue culture. Because of the complex 3D configuration and the presence of various topographies, it is rarely possible to observe and analyze cells within such scaffolds in situ. Thus, we aim to develop scaled down mini-chambers as simplified in vitro simulation systems, to bridge the gap between two-dimensional (2D) cell cultures on structured substrates and three-dimensional (3D) tissue culture. The mini-chambers were manipulated to systematically simulate and evaluate the influences of gravity, topography, fluid flow, and scaffold dimension on three exemplary cell models that play a role in CNS repair (i.e., cortical astrocytes, fibroblasts, and myelinating cultures) within a tubular scaffold created by rolling up a microstructured membrane. Since we use CNS myelinating cultures, we can confirm that the scaffold does not affect neural cell differentiation. It was found that heterogeneous cell distribution within the tubular constructs was caused by a combination of gravity, fluid flow, topography, and scaffold configuration, while cell survival was influenced by scaffold length, porosity, and thickness. This research demonstrates that the mini-chambers represent a viable, novel, scale down approach for the evaluation of complex 3D scaffolds as well as providing a microbioprocessing strategy for tissue engineering and the potential repair of SCI.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Riehle, Dr Mathis and Barnett, Professor Susan and Sun, Dr Tao and Gadegaard, Professor Nikolaj and Donoghue, Dr Peter
Authors: Donoghue, P. S., Sun, T., Gadegaard, N., Riehle, M. O., and Barnett, S. C.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
College of Science and Engineering > School of Engineering > Biomedical Engineering
Journal Name:Molecular Pharmaceutics
Publisher:American Chemical Society
ISSN (Online):1543-8392
Copyright Holders:Copyright © 2014 The Authors
First Published:First published in Molecular Pharmaceutics
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher.

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
481921Micro Engineered Constructs for CNS repairSusan BarnettBiotechnology and Biological Sciences Research Council (BBSRC)BB/G004706/1III -IMMUNOLOGY