Valero Clara, Javierre Etelvina, García-Aznar José Manuel, Gómez-Benito María José
Multiscale in Mechanical and Biological Engineering (M2BE), Aragón Institute of Engineering Research (I3A), University of Zaragoza, Zaragoza, Spain.
Centro Universitario de la Defensa de Zaragoza, Academia General Militar, Zaragoza, Spain.
PLoS One. 2014 Mar 28;9(3):e92774. doi: 10.1371/journal.pone.0092774. eCollection 2014.
Wound healing is a process driven by cells. The ability of cells to sense mechanical stimuli from the extracellular matrix that surrounds them is used to regulate the forces that cells exert on the tissue. Stresses exerted by cells play a central role in wound contraction and have been broadly modelled. Traditionally, these stresses are assumed to be dependent on variables such as the extracellular matrix and cell or collagen densities. However, we postulate that cells are able to regulate the healing process through a mechanosensing mechanism regulated by the contraction that they exert. We propose that cells adjust the contraction level to determine the tissue functions regulating all main activities, such as proliferation, differentiation and matrix production. Hence, a closed-regulatory feedback loop is proposed between contraction and tissue formation. The model consists of a system of partial differential equations that simulates the evolution of fibroblasts, myofibroblasts, collagen and a generic growth factor, as well as the deformation of the extracellular matrix. This model is able to predict the wound healing outcome without requiring the addition of phenomenological laws to describe the time-dependent contraction evolution. We have reproduced two in vivo experiments to evaluate the predictive capacity of the model, and we conclude that there is feedback between the level of cell contraction and the tissue regenerated in the wound.
伤口愈合是一个由细胞驱动的过程。细胞感知其周围细胞外基质机械刺激的能力被用于调节细胞对组织施加的力。细胞施加的应力在伤口收缩中起核心作用,并且已经有了广泛的模型。传统上,这些应力被认为取决于诸如细胞外基质、细胞或胶原蛋白密度等变量。然而,我们推测细胞能够通过由它们所施加的收缩调节的机械传感机制来调节愈合过程。我们提出细胞会调整收缩水平以确定调节所有主要活动(如增殖、分化和基质产生)的组织功能。因此,我们提出在收缩和组织形成之间存在一个封闭的调节反馈回路。该模型由一个偏微分方程组组成,它模拟成纤维细胞、肌成纤维细胞、胶原蛋白和一种通用生长因子的演变,以及细胞外基质的变形。这个模型能够预测伤口愈合结果,而无需添加现象学定律来描述随时间变化的收缩演变。我们重现了两个体内实验来评估该模型的预测能力,并且我们得出结论,细胞收缩水平与伤口中再生的组织之间存在反馈。