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A Multi-Paradigm Modeling Framework to Simulate Dynamic Reciprocity in a Bioreactor

Author

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  • Himanshu Kaul
  • Zhanfeng Cui
  • Yiannis Ventikos

Abstract

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.

Suggested Citation

  • Himanshu Kaul & Zhanfeng Cui & Yiannis Ventikos, 2013. "A Multi-Paradigm Modeling Framework to Simulate Dynamic Reciprocity in a Bioreactor," PLOS ONE, Public Library of Science, vol. 8(3), pages 1-15, March.
  • Handle: RePEc:plo:pone00:0059671
    DOI: 10.1371/journal.pone.0059671
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    1. Min Zhao & Bing Song & Jin Pu & Teiji Wada & Brian Reid & Guangping Tai & Fei Wang & Aihua Guo & Petr Walczysko & Yu Gu & Takehiko Sasaki & Akira Suzuki & John V. Forrester & Henry R. Bourne & Peter N, 2006. "Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-γ and PTEN," Nature, Nature, vol. 442(7101), pages 457-460, July.
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