A two-compartment mechanochemical model of the roles of transforming growth factor β and tissue tension in dermal wound healing

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dc.contributor.author Murphy, Kelly en
dc.contributor.author Hall, CL en
dc.contributor.author McCue, SW en
dc.contributor.author McElwain, DLS en
dc.date.accessioned 2012-03-08T19:37:25Z en
dc.date.issued 2011-03-07 en
dc.identifier.citation J Theor Biol 272(1):145-159 07 Mar 2011 en
dc.identifier.issn 0022-5193 en
dc.identifier.uri http://hdl.handle.net/2292/13492 en
dc.description.abstract The repair of dermal tissue is a complex process of interconnected phenomena, where cellular, chemical and mechanical aspects all play a role, both in an autocrine and in a paracrine fashion. Recent experimental results have shown that transforming growth factor -β (TGFβ) and tissue mechanics play roles in regulating cell proliferation, differentiation and the production of extracellular materials. We have developed a 1D mathematical model that considers the interaction between the cellular, chemical and mechanical phenomena, allowing the combination of TGFβ and tissue stress to inform the activation of fibroblasts to myofibroblasts. Additionally, our model incorporates the observed feature of residual stress by considering the changing zero-stress state in the formulation for effective strain. Using this model, we predict that the continued presence of TGFβ in dermal wounds will produce contractures due to the persistence of myofibroblasts; in contrast, early elimination of TGFβ significantly reduces the myofibroblast numbers resulting in an increase in wound size. Similar results were obtained by varying the rate at which fibroblasts differentiate to myofibroblasts and by changing the myofibroblast apoptotic rate. Taken together, the implication is that elevated levels of myofibroblasts is the key factor behind wounds healing with excessive contraction, suggesting that clinical strategies which aim to reduce the myofibroblast density may reduce the appearance of contractures. en
dc.language English en
dc.publisher Elsevier Ltd en
dc.relation.ispartofseries Journal of Theoretical Biology en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from http://www.sherpa.ac.uk/romeo/issn/0022-5193/ en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.subject Biomechanics en
dc.subject Morphoelasticity en
dc.subject Zero stress states en
dc.subject Myofibroblasts en
dc.title A two-compartment mechanochemical model of the roles of transforming growth factor β and tissue tension in dermal wound healing en
dc.type Journal Article en
dc.identifier.doi 10.1016/j.jtbi.2010.12.011 en
pubs.issue 1 en
pubs.begin-page 145 en
pubs.volume 272 en
dc.rights.holder Copyright: Elsevier Ltd en
dc.identifier.pmid 21168423 en
pubs.end-page 159 en
pubs.publication-status Published en
dc.rights.accessrights http://purl.org/eprint/accessRights/RestrictedAccess en
pubs.subtype Article en
pubs.elements-id 209332 en
pubs.org-id Bioengineering Institute en
pubs.org-id ABI Associates en
pubs.record-created-at-source-date 2011-04-29 en
pubs.dimensions-id 21168423 en

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