| Abstract |
This thesis is divided into four parts. Part 1 provides an overview of the
AMC-BAL research performed between 1995 and 2004 and describes the
optimization of the AMCBAL from the first generation to an improved second
generation device. Furthermore, a comparison between the second generation
AMC-BAL and another European BAL device (MELS CellModule) is presented,
whereas the effect of mild hypothermic preservation for transport purposes
of the AMC-BAL is discussed. In Part 2, mathematical modeling and
computational fluid simulations were used to analyze the AMC-BAL on a
micro and full-scale level in silico. Resulting recommendations for further
improvements of the AMC-BAL were validated in an in vitro study. Part 3
describes the research process of advanced in-depth analysis of cultured
hepatocytes inside the AMC-BAL at three basic bioengineering levels, i.e.
at the level of gene expression, liver metabolical, and histological level.
Furthermore, a comparative study between three primary cell types, i.e.
mature porcine hepatocytes, mature human hepatocytes and fetal human
hepatocytes, herald the transition towards the use of human hepatic cell
lines. Part 4 evaluates the potential of a newly developed, human hepatic
cell line (cBAL111) for application in the AMC-BAL in the setting of an in
vitro and an ex vivo study in an animal model of ALF.
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