O'Dea R D, Osborne J M, El Haj A J, Byrne H M, Waters S L
School of Science and Technology, Nottingham Trent University, Clifton Campus, Nottingham, NG11 8NS, UK,
J Math Biol. 2013 Nov;67(5):1199-225. doi: 10.1007/s00285-012-0587-9. Epub 2012 Sep 18.
In vitro tissue engineering is emerging as a potential tool to meet the high demand for replacement tissue, caused by the increased incidence of tissue degeneration and damage. A key challenge in this field is ensuring that the mechanical properties of the engineered tissue are appropriate for the in vivo environment. Achieving this goal will require detailed understanding of the interplay between cell proliferation, extracellular matrix (ECM) deposition and scaffold degradation. In this paper, we use a mathematical model (based upon a multiphase continuum framework) to investigate the interplay between tissue growth and scaffold degradation during tissue construct evolution in vitro. Our model accommodates a cell population and culture medium, modelled as viscous fluids, together with a porous scaffold and ECM deposited by the cells, represented as rigid porous materials. We focus on tissue growth within a perfusion bioreactor system, and investigate how the predicted tissue composition is altered under the influence of (1) differential interactions between cells and the supporting scaffold and their associated ECM, (2) scaffold degradation, and (3) mechanotransduction-regulated cell proliferation and ECM deposition. Numerical simulation of the model equations reveals that scaffold heterogeneity typical of that obtained from [Formula: see text]CT scans of tissue engineering scaffolds can lead to significant variation in the flow-induced mechanical stimuli experienced by cells seeded in the scaffold. This leads to strong heterogeneity in the deposition of ECM. Furthermore, preferential adherence of cells to the ECM in favour of the artificial scaffold appears to have no significant influence on the eventual construct composition; adherence of cells to these supporting structures does, however, lead to cell and ECM distributions which mimic and exaggerate the heterogeneity of the underlying scaffold. Such phenomena have important ramifications for the mechanical integrity of engineered tissue constructs and their suitability for implantation in vivo.
体外组织工程作为一种潜在工具正在兴起，以满足因组织退化和损伤发生率增加而对替代组织产生的高需求。该领域的一个关键挑战是确保工程组织的力学性能适合体内环境。要实现这一目标，需要详细了解细胞增殖、细胞外基质（ECM）沉积和支架降解之间的相互作用。在本文中，我们使用一个数学模型（基于多相连续体框架）来研究体外组织构建物演化过程中组织生长与支架降解之间的相互作用。我们的模型包含一个细胞群体和培养基，将其建模为粘性流体，以及一个多孔支架和细胞沉积的ECM，将其表示为刚性多孔材料。我们专注于灌注生物反应器系统内的组织生长，并研究在以下因素影响下预测的组织组成如何变化：（1）细胞与支撑支架及其相关ECM之间的差异相互作用，（2）支架降解，以及（3）机械转导调节的细胞增殖和ECM沉积。对模型方程的数值模拟表明，从组织工程支架的[公式：见正文]CT扫描获得的典型支架异质性可导致接种在支架中的细胞所经历的流动诱导机械刺激产生显著变化。这导致ECM沉积出现强烈的异质性。此外，细胞优先粘附于ECM而非人工支架似乎对最终构建物组成没有显著影响；然而，细胞对这些支撑结构的粘附确实导致细胞和ECM分布模仿并夸大了底层支架的异质性。这些现象对工程组织构建物的机械完整性及其体内植入的适用性具有重要影响。
