Novel bioactive polymeric membranes to elicit specific human hepatocyte responses

Abstract

The aim of the paper was the design and development of new bioactive polymeric membranes to be used for the in vitro reconstruction of liver tissue-model [1–2]. Significant efforts have also been made to develop new polymeric materials able to favour the liver reconstruction and to modulate liver cell behaviour. We developed membranes from a polymeric blend of modified polyether-etherketone (PEEK-WC) and polyurethane (PU) by inverse phase technique by using the direct immersionprecipitation method (PEEK-WC-PU) [3]. The morphological and physico-chemical properties of the PEEK-WC-PU membranes were established before their use in the cell culture system. Preliminarily a screening of this new material was performed investigating the specific liver functions in terms of albumin and urea synthesis using primary human hepatocytes (Cambrex Bio Science) cultured on PEEK-WC-PU membranes in comparison with collagen film. The biotransformation functions of human liver cells were evaluated using diclofenac (DIC), a nonsteroidal anti-inflammatory drug that is widely used in painful and inflammatory rheumatic and nonrheumatic conditions. Then the performance of the novel PEEK-WC-PU membranes was validated by using the biohybrid system constituted by human hepatocytes and PEEK-WC-PU membrane in a oxygen permeable membrane bioreactor. Liver specific functions in terms of urea synthesis and total protein secretion was evaluated in the time. Drug biotransformation was also assessed using Diazepam, an anti anxiety agent (benzodiazepines), as model drug. *Corresponding author.