Distributed and Lumped Parameter Models for the Characterization of High Throughput Bioreactors
Distributed and Lumped Parameter Models for the Characterization of High Throughput Bioreactors
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DOI：
10.1371/journal.pone.0162774
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发表时间：
2016-09-26
期刊：
影响因子：
3.7
通讯作者：
Zunino, Paolo
中科院分区：
文献类型：
--
作者：
Iannetti, Laura;D'Urso, Giovanna;Zunino, Paolo
正在开发下一代生物反应器，以在同一流体系统内生成多种基于人类细胞的组织类似物，以更好地概括人类生理学的复杂性和相互联系[1，2]。这些设备的有效开发需要对其相互连接的流体学有深入的了解，以预测营养物质和废物通过结构的运输，并相应地改进设计。在这项工作中，我们专注于一个特定的生物反应器模型，具有多个输入/输出，旨在产生骨软骨构建体，即，一种双相结构，其中一侧本质上是软骨，而另一侧是骨。接下来，我们开发了一种通用的计算方法来模拟可应用于人芯片设备的多室互连系统的微流体。这一目标需要克服计算建模层面的若干挑战。主要的一个包括解决多物理性质的问题，结合在通道中的自由流动与多孔介质中的受阻流。流体动力学还与对流-扩散-反应方程相结合，该方程模拟生物分子在整个系统中的运输及其与活组织和C结构的相互作用。最终，我们的目标是提供一个预测的方法有用的一般器官芯片社区。为此，我们已经开发了一种集总参数的方法，使我们能够分析多单元生物反应器系统的行为与适度的计算工作量，只要一个单一的单元的行为可以充分的特点。
Next generation bioreactors are being developed to generate multiple human cell-based tissue analogs within the same fluidic system, to better recapitulate the complexity and interconnection of human physiology [1, 2]. The effective development of these devices requires a solid understanding of their interconnected fluidics, to predict the transport of nutrients and waste through the constructs and improve the design accordingly. In this work, we focus on a specific model of bioreactor, with multiple input/outputs, aimed at generating osteochondral constructs, i.e., a biphasic construct in which one side is cartilaginous in nature, while the other is osseous. We next develop a general computational approach to model the microfluidics of a multi-chamber, interconnected system that may be applied to human-on-chip devices. This objective requires overcoming several challenges at the level of computational modeling. The main one consists of addressing the multi-physics nature of the problem that combines free flow in channels with hindered flow in porous media. Fluid dynamics is also coupled with advection-diffusion-reaction equations that model the transport of biomolecules throughout the system and their interaction with living tissues and C constructs. Ultimately, we aim at providing a predictive approach useful for the general organ-on-chip community. To this end, we have developed a lumped parameter approach that allows us to analyze the behavior of multi-unit bioreactor systems with modest computational effort, provided that the behavior of a single unit can be fully characterized.