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Development of perfluoroelastomer-based low-sorption microfluidic devices for drug metabolism and toxicity studies

Wang, Mengyang 京都大学 DOI:10.14989/doctor.k24548

2023.03.23

概要

In recent years, the use of microphysiological systems for the evaluation of liver metabolism
and toxicity has gained attention [8, 9]. Microphysiological systems can be considered miniature
systems of artificial liver bioreactors that have been studied. Similar to bioreactors, the perfusion
culture system can supply nutrients and oxygen to wash out metabolic waste [2]. Furthermore,
biochemical and biomechanical stimuli given by the system improve the function of hepatocytes
[3]. Once culturing begins, primary hepatocytes rapidly lose function. However, this can be
mitigated with the addition of microfluidic flow. In fact, under flow conditions, albumin and urea
secretion remains constant for more than 2 weeks, and gene expression of various metabolizing
enzymes and transporters improved, as compared to that in static conditions [10].
Metabolism studies in microphysiological systems are hampered by the absorption of drugs
into the materials used in microfabrication. Polydimethylsiloxane (PDMS) is the commonly used
material because of its biocompatibility, transparency, and excellent molding characteristics, but
the hydrophobic and porous nature of PDMS causes extensive absorption of hydrophobic drugs
[5]. As a result, there is limited information regarding the functional presence of metabolic activity,
as compared to the biological and physiological functions of hepatocytes cultured on chips.
Because of the limitations of PDMS, devices using alternative, non-absorptive materials are now
being explored. Recently, Campbell et al. provided an excellent review on alternative materials
for the fabrication of microphysiological systems [6]. ...

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