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 TGFβ. Our work extends a previously developed model which considers the interactions between fibroblasts and 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 can direct the fibroblasts and control their speed. Here we extend the model by allowing a time varying concentration of TGFβ to alter the properties of the fibroblasts. Thus we are able to simulate experiments which alter the TGFβ profile. Within this model framework we find that most of the known effects of TGFβ, 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 TGFβ. However, we find that by changing fibroblast reorientation rates, consistent with experimental evidence, the alignment of the regenerated tissue can be significantly altered. This provides an explanation for the experimentally observed influence of TGFβ on scarring. keywords: cell flux, cell speed, cell polarization, tissue regeneration, collagen production, fibrin degradation.