Modeling the effects of transforming growth factor-β on extracellular matrix alignment in dermal wound repair

We present a novel mathematical model for collagen deposition and alignment during dermal wound healing, focusing on the regulatory effects of transforming growth factor-ß (TGFß.) Our work extends a previously developed model which considers the interactions between fibroblasts and an extracellular matrix composed of collagen and a fibrin based blood clot, by allowing fibroblasts to orient the collagen matrix, and produce and degrade the extracellular matrix, while the matrix directs the fibroblasts and control their speed, Here we extend the model by allowing a time varying concentration of TGFß to alter the properties of the fibroblasts. Thus we are able to simulate experiments which alter the TGFß profile, Within this model framework we find that most of the known effects of TGFß, i.e., changes in cell motility, cell proliferation and collagen production, are of minor importance to matrix alignment and cannot explain the anti-scarring properties of TGFß. However, we find that by changing fibroblast reorientation rates, consistent with experimental evidence, the alignment of the regenerated tissue can be significantly altered. These data provide an explanation for the experimentally observed influence of TGFß on scarring.