Three-dimensional Numerical Modeling and Computational Fluid Dynamics Simulations to Analyze and Improve Oxygen Availability in the AMC Bioartificial Liver

Abstract

Abstract-A numerical model to investigate fluid flow and oxygen (O 2 ) transport and consumption in the AMCBioartificial 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.

Hemoglobin Regulates the Metabolic, Synthetic, Detoxification, and Biotransformation Functions of Hepatoma Cells Cultured in a Hollow Fiber Bioreactor

“…Computational fluid dynamics has long been used to design and to optimize bioreactors by simultaneously modeling momentum and mass transfer. 7,8 The use of O 2 carriers in the cell culture system, on the other hand, provides a biomimetic approach to recapitulate the in vivo oxygenation environment for many tissue engineering applications. [9][10][11] In particular, hepatic hollow fiber (HF) bioreactors that constitute one type of bioartificial liver assist device (BLAD) suffer from O 2 limited transport mainly due to the low solubility of O 2 in the cell culture medium, long diffusion pathlengths, and high demand for O 2 by the hepatocytes cultured in the extracapillary space (ECS).…”

Liver bioengineering

“…In bioartificial livers (viable hepatocytes housed within man-made synthetic devices), fluid flow, shear stress and its distribution may be relatively easy to study and control with computational fluid dynamics. 74,75 However, conditions in a natural scaffold are not that controllable. To date, there are no studies elucidating the best perfusion and pressures rates in recellularized grafts.…”

“…These perfusion machines also allow the quantification of viability markers. 75 The most used are the traditional enzymatic markers of hepatic damage such as aspartate transaminase (AST) and alanine transaminase (ALT), but there are also some less known markers, such as liver fatty acid-binding protein (L-FABP), glutamate dehydrogenase (GLDH), α-glutathione-S-transferase (α-GST), HA, CK18 and β-galactosidase that can provide additional information on graft viability.…”

Current development of bioreactors for extracorporeal bioartificial liver (Review)

“…151 With further optimization, dead space in the bioreactor was reduced so that the biofunction of liver cells was kept at 80%-90% of day 1 after 3 day cultivation. 152 In addition, Mareels et al 153 reported their application of rheological numerical model for the optimization the distribution of oxygen in the AMC bioreactor. However, it has yet reported the clinical studies with optimized bioreactor AMC.…”