Cheng Gang, Markenscoff Pauline, Zygourakis Kyriacos
Department of Chemical and Biomolecular Engineering, Rice University, Houston, Texas, USA.
Biophys J. 2009 Jul 22;97(2):401-14. doi: 10.1016/j.bpj.2009.03.067.
To provide theoretical guidance for the design and in vitro cultivation of bioartificial tissues, we have developed a multiscale computational model that can describe the complex interplay between cell population and mass transport dynamics that governs the growth of tissues in three-dimensional scaffolds. The model has three components: a transient partial differential equation for the simultaneous diffusion and consumption of a limiting nutrient; a cellular automaton describing cell migration, proliferation, and collision; and equations that quantify how the varying nutrient concentration modulates cell division and migration. The hybrid discrete-continuous model was parallelized and solved on a distributed-memory multicomputer to study how transport limitations affect tissue regeneration rates under conditions encountered in typical bioreactors. Simulation results show that the severity of transport limitations can be estimated by the magnitude of two dimensionless groups: the Thiele modulus and the Biot number. Key parameters including the initial seeding mode, cell migration speed, and the hydrodynamic conditions in the bioreactor are shown to affect not only the overall rate, but also the pattern of tissue growth. This study lays the groundwork for more comprehensive models that can handle mixed cell cultures, multiple nutrients and growth factors, and other cellular processes, such as cell death.
为了给生物人工组织的设计和体外培养提供理论指导，我们开发了一种多尺度计算模型，该模型能够描述细胞群体与质量传输动力学之间复杂的相互作用，这种相互作用决定了三维支架中组织的生长。该模型有三个组成部分：一个用于描述限制性营养物质同时扩散和消耗的瞬态偏微分方程；一个描述细胞迁移、增殖和碰撞的细胞自动机；以及量化营养物质浓度变化如何调节细胞分裂和迁移的方程。这个混合离散 - 连续模型在分布式内存多计算机上并行求解，以研究在典型生物反应器中遇到的条件下，传输限制如何影响组织再生速率。模拟结果表明，传输限制的严重程度可以通过两个无量纲组的大小来估计：西勒模数和毕奥数。包括初始接种模式、细胞迁移速度和生物反应器中的流体动力学条件在内的关键参数不仅会影响整体速率，还会影响组织生长模式。这项研究为能够处理混合细胞培养、多种营养物质和生长因子以及其他细胞过程（如细胞死亡）的更全面模型奠定了基础。
