Numerical investigation of dynamic microorgan devices as drug screening platforms. Part II: Microscale modeling approach and validation

Abstract

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.

Numerical optimization of cell colonization modelling inside scaffold for perfusion bioreactor: A multiscale model

“…By using a numerical protocol based on REV, the scaffold pore architecture is a critical design variable in the prediction of the development of cells. The size of our REV is close to analogue studies on perfusion inside porous media [53][54][55][56][57] i.e. around 5 to 10 mm 3 .In several works a structured pores architecture is studied [53,55,56] .…”

Numerical Investigations of Hepatic Spheroids Metabolic Reactions in a Perfusion Bioreactor

“…(A) Oxygen concentration profile along the spheroid diameter for different mesh numbers. (B) Comparison of computed results of the fluid velocity inside the channel to those reported by Tourlomousis and Chang (2016b). (C) Comparison of the predicted metabolites participating in the urea cycle with the results given by Kuchel et al (1977) (D) Oxygen concentrations are compared with the experimental data obtained by Murphy et al (2017) for three different spheroid sizes.…”

“…From this figure, it can be inferred that results obtained from the grid with 589,006 elements are suitable for further studies and finer grid numbers do not show any significant discrepancies. Also, to validate the finite element code used for the present study, the generated code was used for replicating of the previous study remodeling carried out by Tourlomousis and Chang (2016b). Computed results of the fluid velocity inside the channel are compared with those reported by Tourlomousis and Chang (2016b) showing excellent compatibility (Figure 5B).…”

“…Also, to validate the finite element code used for the present study, the generated code was used for replicating of the previous study remodeling carried out by Tourlomousis and Chang (2016b). Computed results of the fluid velocity inside the channel are compared with those reported by Tourlomousis and Chang (2016b) showing excellent compatibility (Figure 5B). Also, the results of the predicted metabolites participating in the urea cycle were modeled and compared with the results given by Kuchel et al (1977).…”

“…It is also possible to modify the porosity of the hydrogel by using different appropriate hydrogels or applying various conditions of hydrogel cross-linking (Tourlomousis and Chang, 2016b). Modifying the membrane porosity does not affect the perfusion rate of the medium, provided that the peristaltic pump circulates the media at the constant flow rate.…”