Influence of flow rate and scaffold pore size on cell behavior during mechanical stimulation in a flow perfusion bioreactor
Influence of flow rate and scaffold pore size on cell behavior during mechanical stimulation in a flow perfusion bioreactor
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DOI：
10.1002/bit.24424
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发表时间：
2012-06-01
影响因子：
3.8
通讯作者：
O'Brien, F. J.
中科院分区：
文献类型：
--
作者：
McCoy, R. J.;Jungreuthmayer, C.;O'Brien, F. J.
通过流动灌注机械刺激细胞接种支架是用于开发临床适用的骨移植替代物的一种方法。一个关键的挑战是确定刺激的大小，以提高细胞分化，但最大限度地减少细胞脱离支架。在这项研究中，我们采用了一种结合的计算建模和实验方法来研究支架平均孔径如何影响细胞附着形态，并随后影响细胞变形和脱离时，受到流体流动。在灌注生物反应器中，在不同的流速和暴露时间下，通过实验评估了成骨细胞接种的胶原蛋白GAG支架的细胞脱离。发现细胞脱离与流速成正比，与孔径成反比。使用这些数据，推导出一个理论模型，该模型准确地预测细胞脱离作为平均剪切应力、平均孔径和时间的函数。响应于流体流动的细胞变形的计算建模显示，超过与实验上的细胞脱离相关的变形的临界阈值的细胞的百分比，并且这些细胞中的大多数具有桥接形态（横跨孔拉伸的细胞）。这些发现将帮助研究人员优化支架的平均孔径和灌注生物反应器的操作条件，以管理细胞分离时，通过流动灌注机械模拟细胞。Biotechnol. Bioeng. 2012; 109：15831594. (c)2012 Wiley Periodicals，Inc.
Mechanically stimulating cell-seeded scaffolds by flow-perfusion is one approach utilized for developing clinically applicable bone graft substitutes. A key challenge is determining the magnitude of stimuli to apply that enhances cell differentiation but minimizes cell detachment from the scaffold. In this study, we employed a combined computational modeling and experimental approach to examine how the scaffold mean pore size influences cell attachment morphology and subsequently impacts upon cell deformation and detachment when subjected to fluid-flow. Cell detachment from osteoblast-seeded collagenGAG scaffolds was evaluated experimentally across a range of scaffold pore sizes subjected to different flow rates and exposure times in a perfusion bioreactor. Cell detachment was found to be proportional to flow rate and inversely proportional to pore size. Using this data, a theoretical model was derived that accurately predicted cell detachment as a function of mean shear stress, mean pore size, and time. Computational modeling of cell deformation in response to fluid flow showed the percentage of cells exceeding a critical threshold of deformation correlated with cell detachment experimentally and the majority of these cells were of a bridging morphology (cells stretched across pores). These findings will help researchers optimize the mean pore size of scaffolds and perfusion bioreactor operating conditions to manage cell detachment when mechanically simulating cells via flow perfusion. Biotechnol. Bioeng. 2012; 109:15831594. (c) 2012 Wiley Periodicals, Inc.