TY - JOUR
T1 - Numerical investigation of dynamic microorgan devices as drug screening platforms. Part II
T2 - Microscale modeling approach and validation
AU - Tourlomousis, Filippos
AU - Chang, Robert C.
N1 - Publisher Copyright:
© 2016 Wiley Periodicals, Inc.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - The authors have previously reported a rigorous macroscale modeling approach for an in vitro 3D dynamic microorgan device (DMD). This paper represents the second of a two-part model-based investigation where the effect of microscale (single liver cell-level) shear-mediated mechanotransduction on drug biotransformation is deconstructed. Herein, each cell is explicitly incorporated into the geometric model as single compartmentalized metabolic structures. Each cell's metabolic activity is coupled with the microscale hydrodynamic Wall Shear Stress (WSS) simulated around the cell boundary through a semi-empirical polynomial function as an additional reaction term in the mass transfer equations. Guided by the macroscale model-based hydrodynamics, only 9 cells in 3 representative DMD domains are explicitly modeled. Dynamic and reaction similarity rules based on non-dimensionalization are invoked to correlate the numerical and empirical models, accounting for the substrate time scales. The proposed modeling approach addresses the key challenge of computational cost towards modeling complex large-scale DMD-type system with prohibitively high cell densities. Transient simulations are implemented to extract the drug metabolite profile with the microscale modeling approach validated with an experimental drug flow study. The results from the author's study demonstrate the preferred implementation of the microscale modeling approach over that of its macroscale counterpart. Biotechnol. Bioeng. 2016;113: 623-634.
AB - The authors have previously reported a rigorous macroscale modeling approach for an in vitro 3D dynamic microorgan device (DMD). This paper represents the second of a two-part model-based investigation where the effect of microscale (single liver cell-level) shear-mediated mechanotransduction on drug biotransformation is deconstructed. Herein, each cell is explicitly incorporated into the geometric model as single compartmentalized metabolic structures. Each cell's metabolic activity is coupled with the microscale hydrodynamic Wall Shear Stress (WSS) simulated around the cell boundary through a semi-empirical polynomial function as an additional reaction term in the mass transfer equations. Guided by the macroscale model-based hydrodynamics, only 9 cells in 3 representative DMD domains are explicitly modeled. Dynamic and reaction similarity rules based on non-dimensionalization are invoked to correlate the numerical and empirical models, accounting for the substrate time scales. The proposed modeling approach addresses the key challenge of computational cost towards modeling complex large-scale DMD-type system with prohibitively high cell densities. Transient simulations are implemented to extract the drug metabolite profile with the microscale modeling approach validated with an experimental drug flow study. The results from the author's study demonstrate the preferred implementation of the microscale modeling approach over that of its macroscale counterpart. Biotechnol. Bioeng. 2016;113: 623-634.
KW - 3D bioprinting
KW - Bioreactor
KW - HepG 2 cells
KW - Liver-on-a-chip
KW - Mechanotransduction
KW - Tissue-on-a-chip
UR - http://www.scopus.com/inward/record.url?scp=84955732594&partnerID=8YFLogxK
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U2 - 10.1002/bit.25824
DO - 10.1002/bit.25824
M3 - Article
C2 - 26333066
AN - SCOPUS:84955732594
SN - 0006-3592
VL - 113
SP - 623
EP - 634
JO - Biotechnology and Bioengineering
JF - Biotechnology and Bioengineering
IS - 3
ER -