Author(s): Nedredal GI, Amiot BP, Nyberg P, LuebkeWheeler J, Lillegard JB,
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Abstract This study was designed to determine optimal operating conditions of a bioartificial liver (BAL) based on mass transfer of representative hepatotoxins and mediators of immune damage. A microprocessor-controlled BAL was used to study mass transfer between patient and cell compartments separated by a hollow fiber membrane. Membrane permeability (70, 150, or 400 kDa molecular weight cut-off-MWCO), membrane convection (high: 50 mL/min; medium: 25 mL/min; low: 10 mL/min; diffusion: 0 mL/min), and albumin concentration in the cell compartment (0.5 or 5 g\%) were considered for a total of 24 test conditions. Initially, the patient compartment contained pig plasma supplemented with ammonia (0.017 kDa), unconjugated bilirubin (0.585 kDa), conjugated bilirubin (0.760 kDa), TNF-alpha (17 kDa), pig albumin (67 kDa), pig IgG (147 kDa), and pig IgM (900 kDa). Mass transfer of each substance was determined by its rate of appearance in the cell compartment. Membrane fouling was assessed by dextran polymer technique. Of the three tested variables (membrane pore size, convection, and albumin concentration), membrane permeability had the greatest impact on mass transfer (P < 0.001). Mass transfer of all toxins was greatest under high convection with a 400 kDa membrane. Transfer of IgG and IgM was insignificant under all conditions. Bilirubin transfer was increased under high albumin conditions (P = 0.055). Fouling of membranes ranged from 7\% (400 kDa), 24\% (150 kDa) to 62\% (70 kDa) during a 2-h test interval. In conclusion, optimal toxin removal was achieved under high convection with a 400-kDa membrane, a condition which should provide adequate immunoprotection of hepatocytes in the BAL.
This article was published in Biotechnol Bioeng
and referenced in Journal of Bioequivalence & Bioavailability