A multi-paradigm modeling framework to simulate dynamic reciprocity in a bioreactor.

A multi-paradigm modeling framework to simulate dynamic reciprocity in a bioreactor.
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DOI:
10.1371/journal.pone.0059671
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Ventikos Y
Ventikos Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kaul H;Cui Z;Ventikos Y

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尽管有许多技术进步,生物反应器仍然主要被用作功能黑匣子,在那里反复试验最终会产生理想的细胞结果。研究人员应用了各种计算方法来了解这种设备的内部动力学对整体细胞生长的影响,但由于潜在方法固有的局限性,这些模型不能提供关于系统动力学的全面视角。在这项研究中,提出了一种新颖的多范例建模平台,能够模拟细胞与其微环境之间的动态双向关系。设计建模平台需要将基于代理的建模平台与交通现象计算建模框架充分结合和耦合。为了展示能力,该平台被用来研究生物反应器参数对整体细胞群体行为的影响,反之亦然。为了实现这一目标,构建了虚拟生物反应器并进行了播种。虚拟细胞在一系列规则的指导下,包括模拟生物反应器内的质量传输以及与细胞相关的概率参数,能够显示一系列行为,如增殖、迁移、趋化和凋亡。通过这种方式,该平台不仅捕捉到了生物反应器传输过程对细胞行为的影响,而且还捕捉到了细胞活动对同一局部质量传输的影响,从而影响了整体细胞的生长。通过在虚拟直观室中模拟细胞的趋化性,并将模拟结果与实验模拟结果进行比较,验证了该平台的有效性。文中给出的结果与已发表的类似风味的模型一致。该建模平台可作为优化生物反应器设计规范的概念选择工具。
Despite numerous technology advances, bioreactors are still mostly utilized as functional black-boxes where trial and error eventually leads to the desirable cellular outcome. Investigators have applied various computational approaches to understand the impact the internal dynamics of such devices has on overall cell growth, but such models cannot provide a comprehensive perspective regarding the system dynamics, due to limitations inherent to the underlying approaches. In this study, a novel multi-paradigm modeling platform capable of simulating the dynamic bidirectional relationship between cells and their microenvironment is presented. Designing the modeling platform entailed combining and coupling fully an agent-based modeling platform with a transport phenomena computational modeling framework. To demonstrate capability, the platform was used to study the impact of bioreactor parameters on the overall cell population behavior and vice versa. In order to achieve this, virtual bioreactors were constructed and seeded. The virtual cells, guided by a set of rules involving the simulated mass transport inside the bioreactor, as well as cell-related probabilistic parameters, were capable of displaying an array of behaviors such as proliferation, migration, chemotaxis and apoptosis. In this way the platform was shown to capture not only the impact of bioreactor transport processes on cellular behavior but also the influence that cellular activity wields on that very same local mass transport, thereby influencing overall cell growth. The platform was validated by simulating cellular chemotaxis in a virtual direct visualization chamber and comparing the simulation with its experimental analogue. The results presented in this paper are in agreement with published models of similar flavor. The modeling platform can be used as a concept selection tool to optimize bioreactor design specifications.
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