Humphrey J D, Wells P B, Baek S, Hu J-J, McLeroy K, Yeh A T
Department of Biomedical Engineering, Texas A&M University, 337 Zachry Engineering Center, 3120 TAMU, College Station, TX 77843-3120, USA,
Biomech Model Mechanobiol. 2008 Aug;7(4):323-34. doi: 10.1007/s10237-007-0099-5. Epub 2007 Aug 14.
Many cell types produce, remodel, and degrade extracellular matrix in response to diverse stimuli, including mechanical loads. Much is known about the molecular biology and biochemistry of the deposition and degradation of collagen, the primary structural constituent of the extracellular matrix in many tissues, yet there has been little modeling of the associated mechanobiology. For example, we do not have quantitative descriptions, or rules, for the kinetics of collagen turnover as a function of altered mechanical loading and we do not know what governs the orientation and pre-stretch at which new fibers are incorporated within extant tissue. In this paper, we use a constrained mixture theory for growth and remodeling of planar soft tissues to motivate a new experimental approach for investigating competing hypotheses on, for example, how new collagen is aligned by synthetic cells. In particular, because stress and strain fields can be homogeneous in a central region of a biaxially tested tissue, and because biaxial testing admits diverse protocols wherein equal stresses can be imposed in the presence of unequal strains or stresses can be maintained in the absence of strain, we report simulations that illustrate the potential utility of biaxial culture studies. Finally, we describe the associated design of a computer-controlled system that allows intravital microscopic quantification of collagen density, orientation, and cross-linking at various stages during the adaptation of a native tissue or the development of a tissue engineered equivalent, each subjected to well controlled biaxial loads.
许多细胞类型会响应包括机械负荷在内的多种刺激，产生、重塑并降解细胞外基质。对于许多组织中细胞外基质的主要结构成分——胶原蛋白的沉积和降解的分子生物学及生物化学，我们已经了解很多，但相关的力学生物学建模却很少。例如，我们没有关于胶原蛋白更新动力学随机械负荷改变的定量描述或规则，也不知道是什么决定了新纤维在现有组织中掺入时的取向和预拉伸。在本文中，我们使用一种用于平面软组织生长和重塑的约束混合理论，来推动一种新的实验方法，以研究例如合成细胞如何使新胶原蛋白排列等相互竞争的假设。特别是，由于在双轴测试组织的中心区域应力和应变场可以是均匀的，并且由于双轴测试允许采用多种方案，即在不等应变的情况下可以施加相等的应力，或者在无应变的情况下可以维持应力，我们报告了一些模拟，这些模拟说明了双轴培养研究的潜在效用。最后，我们描述了一个计算机控制系统的相关设计，该系统能够在天然组织适应或组织工程等效物发育的各个阶段，对胶原蛋白密度、取向和交联进行活体显微镜定量分析，每个阶段都受到良好控制的双轴负荷。
