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

Type
Article

Authors
Murphy, Kelly E.
Hall, Cameron L.
McCue, Scott W.
Sean McElwain, D.L.

KAUST Grant Number
KUK-C1-013-04

Date
2011-03

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 (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.

Citation
Murphy 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.

Acknowledgements
This 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.

Publisher
Elsevier BV

Journal
Journal of Theoretical Biology

DOI
10.1016/j.jtbi.2010.12.011

PubMed ID
21168423

Permanent link to this record