Cheng Gang, Youssef Belgacem B, Markenscoff Pauline, Zygourakis Kyriacos
Department of Chemical and Biomolecular Engineering, Rice University, Houston, Texas 77251-1892, USA.
Biophys J. 2006 Feb 1;90(3):713-24. doi: 10.1529/biophysj.105.063701. Epub 2005 Nov 18.
The development and testing of a discrete model describing the dynamic process of tissue growth in three-dimensional scaffolds is presented. The model considers populations of cells that execute persistent random walks on the computational grid, collide, and proliferate until they reach confluence. To isolate the effect of population dynamics on tissue growth, the model assumes that nutrient and growth factor concentrations remain constant in space and time. Simulations start either by distributing the seed cells uniformly and randomly throughout the scaffold, or from an initial condition designed to simulate the migration and cell proliferation phase of wound healing. Simulations with uniform seeding show that cell migration enhances tissue growth by counterbalancing the adverse effects of contact inhibition. This beneficial effect, however, diminishes and disappears completely for large migration speeds. By contrast, simulations with the "wound" seeding mode show a continual enhancement of tissue regeneration rates with increasing cell migration speeds. We conclude that cell locomotory parameters and the spatial distribution of seed cells can have profound effects on the dynamics of the process and, consequently, on the pattern and rates of tissue growth. These results can guide the design of experiments for testing the effectiveness of biomimetic modifications for stimulating tissue growth.
本文介绍了一种描述三维支架中组织生长动态过程的离散模型的开发与测试。该模型考虑了在计算网格上进行持续随机游走、碰撞并增殖直至达到汇合状态的细胞群体。为了分离群体动态对组织生长的影响,模型假设营养物质和生长因子浓度在空间和时间上保持恒定。模拟开始时,要么将种子细胞均匀随机地分布在整个支架中,要么从旨在模拟伤口愈合迁移和细胞增殖阶段的初始条件开始。均匀播种的模拟表明,细胞迁移通过平衡接触抑制的不利影响来促进组织生长。然而,对于较大的迁移速度,这种有益效果会减弱并完全消失。相比之下,“伤口”播种模式的模拟表明,随着细胞迁移速度的增加,组织再生率会持续提高。我们得出结论,细胞运动参数和种子细胞的空间分布会对该过程的动态产生深远影响,进而影响组织生长的模式和速率。这些结果可为测试仿生修饰刺激组织生长有效性的实验设计提供指导。