A two-compartment mechanochemical model of the roles of transforming growth factor and tissue tension in dermal wound healing
KAUST Grant NumberKUK-C1-013-04
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AbstractThe 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 (TGF β) 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 TGF β 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 TGF β in dermal wounds will produce contractures due to the persistence of myofibroblasts; in contrast, early elimination of TGF β 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. © 2010 Elsevier Ltd.
CitationMurphy KE, Hall CL, McCue SW, Sean McElwain DL (2011) A two-compartment mechanochemical model of the roles of transforming growth factor and tissue tension in dermal wound healing. Journal of Theoretical Biology 272: 145–159. Available: http://dx.doi.org/10.1016/j.jtbi.2010.12.011.
SponsorsThis research was supported under the Australian Research Council's Discovery Projects funding scheme (Project no. DP0878011) and by the Institute of Health and Biomedical Innovation. C.L.H. is a member of the Oxford Centre for Collaborative Applied Mathematics (OCCAM) where his work is supported by Award No. KUK-C1-013-04, made by King Abdullah University of Science and Technology.
JournalJournal of Theoretical Biology
CollectionsPublications Acknowledging KAUST Support
- A fibrocontractive mechanochemical model of dermal wound closure incorporating realistic growth factor kinetics.
- Authors: Murphy KE, Hall CL, Maini PK, McCue SW, McElwain DL
- Issue date: 2012 May
- Modeling the effects of transforming growth factor-beta on extracellular matrix alignment in dermal wound repair.
- Authors: Dallon JC, Sherratt JA, Maini PK
- Issue date: 2001 Jul-Aug
- Clinical strategies for the alleviation of contractures from a predictive mathematical model of dermal repair.
- Authors: Murphy KE, McCue SW, McElwain DL
- Issue date: 2012 Mar-Apr
- Control of wound contraction. Basic and clinical features.
- Authors: Nedelec B, Ghahary A, Scott PG, Tredget EE
- Issue date: 2000 May
- Role of wound healing myofibroblasts on re-epithelialization of human skin.
- Authors: Moulin V, Auger FA, Garrel D, Germain L
- Issue date: 2000 Feb