Objective To obtain primary porcine hepatocyte cultures and determine rate equations for oxygen consumption and other metabolic reactions in various culture media and in liver failure serum.To perform hydrodynamic optimisation and obtain macroscopic transfer models of specific bioreactors containing immobilised primary porcine hepatocytes. To evaluate bioreactor function in vivo model of liver failure.Engineering design techniques and mathematical analysis in conjunction with relevant cell biology and clinical experience will be employed to develop optimised hepatocyte bioreactors for treatment of fulminant hepatic failure (FHF). Primary porcine hepatocytes will be obtained and evaluated in static cultures using different culture media, normal blood plasma and FHF plasma. Cell viability will be assessed by lactate dehydrogenase release and function by cytochrome P450 content, activities of P450 isoenzymes, urea synthesis and changes in reduced glutathione content. Rate equations for several liver dependent metabolic functions will be obtained in a smallscale flow reactor seeded with porcine hepatocytes. The influence of metabolite concentrations and physical operatic;, parameters ( e.g. shear rate. cell density. pH) will be studied. A novel oxystat apparatus will be used to determine cellular oxygen consumption during the critical phase of cell attachment to selected substrata as well as in the post-attachment phase of operation. These fundamental properties will enable the development of macroscopic mass transfer models of two existing bioreactor designs. Both designs utilise fibre technology to provide integral oxygenation. Fluid dynamic optimisation of these devices will he carried out and scaling rules established for bioreactor scale-up. Long term in bitro testing of the bioreactors will be performed with different culture media, normal plasma and FHF plasma. Finally, a scaled-up design will be evaluated in an animal model of FHR. Important aspects of this latter task are the establishment of a stable model of FHF and successful integration of the bioreactor and associated plasmapheresis system in the extra-corporal circuit. Fields of science engineering and technologyenvironmental biotechnologybioremediationbioreactorsnatural sciencesmathematicspure mathematicsmathematical analysisnatural sciencesbiological sciencescell biologynatural sciencesphysical sciencesclassical mechanicsfluid mechanicsfluid dynamicsmedical and health sciencesmedical biotechnologytissue engineeringbioartificial liver Programme(s) FP4-BIOMED 2 - Specific research, technological development and demonstration programme in the field of biomedicine and health, 1994-1998 Topic(s) 2.5 - Cellular engineering Call for proposal Data not available Funding Scheme CSC - Cost-sharing contracts Coordinator University of Strathclyde EU contribution No data Address 106 Rottenrow G4 0NW Glasgow United Kingdom See on map Total cost No data Participants (4) Sort alphabetically Sort by EU Contribution Expand all Collapse all Humboldt-Universität zu Berlin Germany EU contribution No data Address 1,AUGUSTENBURGER PLATZ 13353 BERLIN See on map Total cost No data National and Kapodistrian University of Athens Greece EU contribution No data Address 17,AG THOMA STREET 115 27 ATHENS See on map Total cost No data University of Edinburgh United Kingdom EU contribution No data Address LAURISTON PLACE EH3 9YW EDINBURGH See on map Total cost No data Università degli Studi della Calabria Italy EU contribution No data Address Via Pietro Bucci 87030 Arcavacata di Rende See on map Total cost No data