Dallon J C, Sherratt J A, Maini P K
Department of Mathematics, Brigham Young University, Provo, Utah, USA.
Wound Repair Regen. 2001 Jul-Aug;9(4):278-86. doi: 10.1046/j.1524-475x.2001.00278.x.
We present a novel mathematical model for collagen deposition and alignment during dermal wound healing, focusing on the regulatory effects of transforming growth factor-beta (TGFbeta.) 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 TGFbeta to alter the properties of the fibroblasts. Thus we are able to simulate experiments which alter the TGFbeta profile. Within this model framework we find that most of the known effects of TGFbeta, 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 TGFbeta. 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 TGFbeta on scarring.
我们提出了一种用于皮肤伤口愈合过程中胶原蛋白沉积和排列的新型数学模型，重点关注转化生长因子-β（TGFβ）的调节作用。我们的工作扩展了先前开发的模型，该模型考虑了成纤维细胞与由胶原蛋白和基于纤维蛋白的血凝块组成的细胞外基质之间的相互作用，通过允许成纤维细胞使胶原蛋白基质定向，并产生和降解细胞外基质，而基质则引导成纤维细胞并控制其速度。在这里，我们通过允许随时间变化的TGFβ浓度改变成纤维细胞的特性来扩展模型。因此，我们能够模拟改变TGFβ分布的实验。在这个模型框架内，我们发现TGFβ的大多数已知作用，即细胞运动性、细胞增殖和胶原蛋白产生的变化，对基质排列的重要性较小，无法解释TGFβ的抗瘢痕形成特性。然而，我们发现，通过改变成纤维细胞的重新定向速率，与实验证据一致，可以显著改变再生组织的排列。这些数据为实验观察到的TGFβ对瘢痕形成的影响提供了解释。
