A mechanicochemical model of the roles of TGFβ and tissue tension in dermal wound healing

Abstract

The repair of dermal tissue involves a complex process of interconnected phenomena, where cellular, chemical and mechanical aspects all play a role, both in an autocrine and paracrine fashion. Recent experimental results have shown that transforming growth factor β (TGFβ) and tissue mechanics play roles in regulating cell proliferation, differentiation and production of extracellular materials. We have developed a 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, as well as incorporating the observed feature of residual stress and zero-stress states into the formulation for effective strain. Simulations of the system demonstrated that the prolonged presence of TGFβ delayed normal healing by decreasing the local fibroblast density by transforming fibroblast to myofibroblasts. Ensuring there was an influx of fibroblasts to compensate for those lost via differentiation to myofibroblasts was able to rescue normal healing. In addition, under these conditions the continued presence of TGFβ was predicted to produce contractures due to the persistence of myofibroblasts, as well as dense collagenous or hypertrophic scarring. Furthermore, early elimination of TGFβ resulted in an increase in wound size.