The interplay between tissue growth and scaffold degradation in engineered tissue constructs
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Mathematical Biology
The interplay between tissue growth and scaffold degradation in engineered tissue constructs R. D. O’Dea · J. M. Osborne · A. J. El Haj · H. M. Byrne · S. L. Waters
Received: 22 March 2012 / Revised: 31 August 2012 © Springer-Verlag 2012
Abstract In vitro tissue engineering is emerging as a potential tool to meet the high demand for replacement tissue, caused by the increased incidence of tissue degeneration and damage. A key challenge in this field is ensuring that the mechanical properties of the engineered tissue are appropriate for the in vivo environment. Achieving this goal will require detailed understanding of the interplay between cell proliferation, extracellular matrix (ECM) deposition and scaffold degradation. In this paper, we use a mathematical model (based upon a multiphase continuum framework) to investigate the interplay between tissue growth and scaffold degradation during tissue construct evolution in vitro. Our model accommodates a cell population and culture medium, modelled as viscous fluids, together with a porous scaffold and ECM
R. D. O’Dea and J. M. Osborne are the ioint first authors. R. D. O’Dea (B) School of Science and Technology, Nottingham Trent University, Clifton Campus, Nottingham NG11 8NS, UK e-mail: [email protected] J. M. Osborne · H. M. Byrne Department of Computer Science, University of Oxford, Wolfson Building, Parks Road, Oxford OX1 3QD, UK A. J. El Haj Institute for Science and Technology in Medicine, Keele University, Guy Hilton Research Centre, Stoke-on-Trent ST4 7QB, UK H. M. Byrne Oxford Centre for Collaborative Applied Mathematics, Mathematical Institute, Gibson Building, Oxford OX2 6HA, UK S. L. Waters Oxford Centre for Industrial and Applied Mathematics, Mathematical Institute, 24-29 St Giles’, Oxford OX1 3LB, UK
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deposited by the cells, represented as rigid porous materials. We focus on tissue growth within a perfusion bioreactor system, and investigate how the predicted tissue composition is altered under the influence of (1) differential interactions between cells and the supporting scaffold and their associated ECM, (2) scaffold degradation, and (3) mechanotransduction-regulated cell proliferation and ECM deposition. Numerical simulation of the model equations reveals that scaffold heterogeneity typical of that obtained from μCT scans of tissue engineering scaffolds can lead to significant variation in the flow-induced mechanical stimuli experienced by cells seeded in the scaffold. This leads to strong heterogeneity in the deposition of ECM. Furthermore, preferential adherence of cells to the ECM in favour of the artificial scaffold appears to have no significant influence on the eventual construct composition; adherence of cells to these supporting structures does, however, lead to cell and ECM distributions which mimic and exaggerate the heterogeneity of the underlying scaffold. Such phenomena have important ramifications for the mechanical integrity of engineered tissue constructs and their suitability fo
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