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Distributed and Lumped Parameter Models for the Characterization of High Throughput Bioreactors

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.


Streamlines in the 1- unit model with the GelMA scaffold.
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pone.0162774.g005: Streamlines in the 1- unit model with the GelMA scaffold.

Mentions: We observe that for all the configurations, the fluid is driven by the pressure gradient to move toward the upper chamber (Fig 5). The flow split obtained by applying the different flow pairs are reported in Tables 3 and 4 for the GelMA and PLLA case, respectively. The comparison of the outlet flow rates for the two scaffolds highlighted opposite outcomes in terms of flow mixing. Indeed, while not significant flow mixing was found for the GelMA scaffold, a significant mixing occurs in the PLLA case. As expected, the maximum mixing (that is 42.9%) occurs with different input fluid flow rates (1 and 2 ml/day at the upper and lower inlet, respectively).


Distributed and Lumped Parameter Models for the Characterization of High Throughput Bioreactors
Streamlines in the 1- unit model with the GelMA scaffold.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5036894&req=5

pone.0162774.g005: Streamlines in the 1- unit model with the GelMA scaffold.
Mentions: We observe that for all the configurations, the fluid is driven by the pressure gradient to move toward the upper chamber (Fig 5). The flow split obtained by applying the different flow pairs are reported in Tables 3 and 4 for the GelMA and PLLA case, respectively. The comparison of the outlet flow rates for the two scaffolds highlighted opposite outcomes in terms of flow mixing. Indeed, while not significant flow mixing was found for the GelMA scaffold, a significant mixing occurs in the PLLA case. As expected, the maximum mixing (that is 42.9%) occurs with different input fluid flow rates (1 and 2 ml/day at the upper and lower inlet, respectively).

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.