The interplay between tissue growth and scaffold degradation in engineered tissue constructs

Handle URI:
http://hdl.handle.net/10754/599926
Title:
The interplay between tissue growth and scaffold degradation in engineered tissue constructs
Authors:
O’Dea, R. D.; Osborne, J. M.; El Haj, A. J.; Byrne, H. M.; Waters, S. L.
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 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 for implantation in vivo. © 2012 Springer-Verlag.
Citation:
O’Dea RD, Osborne JM, El Haj AJ, Byrne HM, Waters SL (2012) The interplay between tissue growth and scaffold degradation in engineered tissue constructs. Journal of Mathematical Biology 67: 1199–1225. Available: http://dx.doi.org/10.1007/s00285-012-0587-9.
Publisher:
Springer Nature
Journal:
Journal of Mathematical Biology
KAUST Grant Number:
KUK-013-04
Issue Date:
18-Sep-2012
DOI:
10.1007/s00285-012-0587-9
PubMed ID:
22986893
Type:
Article
ISSN:
0303-6812; 1432-1416
Sponsors:
This work was supported by funding from the EPSRC in the form of a Ph.D studentship (RDO) and an Advanced Research Fellowship (SLW). It was also supported by the EPSRC/BBSRC-funded OCISB project BB/D020190/1 (JMO), and based on work supported in part by Award KUK-013-04 made by King Abdullah University of Science and Technology (HMB). We are also grateful to E. Baas, ISTM, Keele University for the provision of experimental data.
Appears in Collections:
Publications Acknowledging KAUST Support

Full metadata record

DC FieldValue Language
dc.contributor.authorO’Dea, R. D.en
dc.contributor.authorOsborne, J. M.en
dc.contributor.authorEl Haj, A. J.en
dc.contributor.authorByrne, H. M.en
dc.contributor.authorWaters, S. L.en
dc.date.accessioned2016-02-28T06:32:35Zen
dc.date.available2016-02-28T06:32:35Zen
dc.date.issued2012-09-18en
dc.identifier.citationO’Dea RD, Osborne JM, El Haj AJ, Byrne HM, Waters SL (2012) The interplay between tissue growth and scaffold degradation in engineered tissue constructs. Journal of Mathematical Biology 67: 1199–1225. Available: http://dx.doi.org/10.1007/s00285-012-0587-9.en
dc.identifier.issn0303-6812en
dc.identifier.issn1432-1416en
dc.identifier.pmid22986893en
dc.identifier.doi10.1007/s00285-012-0587-9en
dc.identifier.urihttp://hdl.handle.net/10754/599926en
dc.description.abstractIn 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 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 for implantation in vivo. © 2012 Springer-Verlag.en
dc.description.sponsorshipThis work was supported by funding from the EPSRC in the form of a Ph.D studentship (RDO) and an Advanced Research Fellowship (SLW). It was also supported by the EPSRC/BBSRC-funded OCISB project BB/D020190/1 (JMO), and based on work supported in part by Award KUK-013-04 made by King Abdullah University of Science and Technology (HMB). We are also grateful to E. Baas, ISTM, Keele University for the provision of experimental data.en
dc.publisherSpringer Natureen
dc.subjectMultiphaseen
dc.subjectPerfusion bioreactoren
dc.subjectScaffold heterogeneityen
dc.titleThe interplay between tissue growth and scaffold degradation in engineered tissue constructsen
dc.typeArticleen
dc.identifier.journalJournal of Mathematical Biologyen
dc.contributor.institutionNottingham Trent University, Nottingham, United Kingdomen
dc.contributor.institutionUniversity of Oxford, Oxford, United Kingdomen
dc.contributor.institutionKeele University, Keele, United Kingdomen
kaust.grant.numberKUK-013-04en

Related articles on PubMed

All Items in KAUST are protected by copyright, with all rights reserved, unless otherwise indicated.