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. 2006 Nov;34(11):1729-44.
doi: 10.1007/s10439-006-9169-6. Epub 2006 Oct 10.

Three-dimensional numerical modeling and computational fluid dynamics simulations to analyze and improve oxygen availability in the AMC bioartificial liver

Affiliations

Three-dimensional numerical modeling and computational fluid dynamics simulations to analyze and improve oxygen availability in the AMC bioartificial liver

Guy Mareels et al. Ann Biomed Eng. 2006 Nov.

Abstract

A numerical model to investigate fluid flow and oxygen (O(2)) transport and consumption in the AMC-Bioartificial Liver (AMC-BAL) was developed and applied to two representative micro models of the AMC-BAL with two different gas capillary patterns, each combined with two proposed hepatocyte distributions. Parameter studies were performed on each configuration to gain insight in fluid flow, shear stress distribution and oxygen availability in the AMC-BAL. We assessed the function of the internal oxygenator, the effect of changes in hepatocyte oxygen consumption parameters in time and the effect of the change from an experimental to a clinical setting. In addition, different methodologies were studied to improve cellular oxygen availability, i.e. external oxygenation of culture medium, culture medium flow rate, culture gas oxygen content (pO(2)) and the number of oxygenation capillaries. Standard operating conditions did not adequately provide all hepatocytes in the AMC-BAL with sufficient oxygen to maintain O(2) consumption at minimally 90% of maximal uptake rate. Cellular oxygen availability was optimized by increasing the number of gas capillaries and pO(2) of the oxygenation gas by a factor two. Pressure drop over the AMC-BAL and maximal shear stresses were low and not considered to be harmful. This information can be used to increase cellular efficiency and may ultimately lead to a more productive AMC-BAL.

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Figures

Figure 1.
Figure 1.
Longitudinal (left) and transverse (right) view of the internal geometry of the AMC-BAL with a – gas outlet; b – gas inlet; c – plasma inlet port; d – plasma outlet port; e – first mat segment; f – interspace; g – second mat segment; h – polyurethane potting to separate gas and fluid compartment; i – inner core; j – inflow zone; k – outflow zone; l – polycarbonate housing; m – gas capillaries; n – inter-capillary space through which plasma flows. The inline and triangular micro models are designated.
Figure 2.
Figure 2.
AMC-BAL micro models. Upper left, inline micro model; upper right, triangular micro model (c – capillary wall, M – non-woven matrix mat, f – inter-capillary space); lower left, inline micro model with double number of capillaries; lower right, triangular micro model with double number of capillaries.
Figure 3.
Figure 3.
Determination of the correction factor for O2 diffusion through the non-woven polyester mat. (A) pO2 distribution [mmHg] on modified inline micro model (polyester fibers drawn) under standard boundary conditions, no medium flow; (B) identical pO2 distribution [mmHg] obtained with identical simulation settings, but with mat as homogeneous medium with an adjusted diffusion constant (with a factor of 0.85) to account for hindered diffusion.
Figure 4.
Figure 4.
Colorimetric contour plot of velocity magnitudes (m/s, left legend, upper part 1) and shear stress levels (Pa, right legend, lower part 2) in a transverse plane midway through the first mat segment, in the reference case (case 1) of an inline micro model with hepatocyte distribution 1 (A1 and A2 resp.) and in a triangular micro model with hepatocyte distribution 2 and with double number of capillaries (case 10–11) (B1 and B2 resp.).
Figure 5.
Figure 5.
Colorimetric contour plot of pO2 (mmHg, left legend, upper part 1) and effective hepatocyte utilization ratio Vratio (dimensionless, right legend, lower part 2) in a transverse plane midway through the first mat segment, in the reference case (case 1) of an inline micro model with hepatocyte distribution 1 (A1 and A2 resp.) and in a triangular micro model with hepatocyte distribution 2 and with double number of capillaries and doubled culture gas pO2 (case 11) (B1 and B2 resp.) (Note: B1 different scale compared to A1).

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