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Biomaterials
Volume 26, Issue 33 , November 2005, Pages 6625-6634
doi:10.1016/j.biomaterials.2005.04.021 
Copyright © 2005 Elsevier Ltd All rights reserved.
Effect of isoliquiritigenin on viability and differentiated functions of human hepatocytes maintained on PEEK-WC–polyurethane membranes
Loredana De Bartoloa,  ,  , Sabrina Morellia, Maria Carmela Galloa, Carla Campanaa, Giancarlo Stattib, Maria Rendea, Simona Salernoc and Enrico Driolia
aInstitute on Membrane Technology, National Research Council of Italy, ITM-CNR, c/o University of Calabria, via P. Bucci cubo 17/C, 87030 Rende (CS), Italy
bDepartment of Pharmaceutical Sciences, University of Calabria, via P. Bucci, 87030 Rende (CS), Italy
cDepartment of Pharmaco-Biology, University of Calabria, via P. Bucci, 87030 Rende (CS), Italy
Received 19 January 2005; accepted 7 April 2005. Available online 31 May 2005.
Abstract
In this study, we tested the ability of microporous membranes synthesised from a polymeric blend of modified polyetheretherketone (PEEK-WC) and polyurethane (PU) to support long-term maintenance and differentiation of human liver cells. The effect of  isoliquiritigenin (ISL), which is a component of liquorice extract, exhibiting growth stimulatory and antiproliferative dose-dependent effect was investigated by comparing cultures treated with ISL with those untreated.
To this purpose, flat-sheet membranes were prepared by a blend of PEEK-WC and PU polymers by phase inverse technique. The morphological and physico-chemical properties were characterised, respectively, by scanning electron microscopy and water contact angle measurements.
Human hepatocytes cultured on PEEK-WC–PU membranes were constant up to 1 month albumin production and urea synthesis as well as the synthesis of total proteins. The liver-specific functions were expressed at high levels when cells were cultured on membranes with respect to collagen. Also the biotransformation functions were maintained for all culture periods: the ISL elimination rate increased during the culture time and high values were measured up to 22 days. Thereafter, a decrease was observed. ISL stimulated the proliferation of hepatocytes cultured on both substrata but did not affect their liver-specific functions. Hepatocytes cultured on PEEK-WC–PU membranes responded very well to ISL and expressed high levels of P450 cytochrome.
These results demonstrated that long-term maintenance of human liver differentiation can be achieved on PEEK-WC–PU membranes. The incubation with ISL at the investigated concentration could stimulate the proliferation of human hepatocytes in biohybrid systems.
Keywords: Membrane; Human hepatocyte; Liver-specific functions; Biotransformation; Isoliquiritigenin
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