Development of a new flat-bottom model of bioartificial liver (BAL): its adequacy to liver microorgans (LMOs) as biological component

PIZARRO, M.D., MEDIAVILLA, M.G., SCANDIZZI, A., RODRÍGUEZ, J.V. Y MAMPRIN, M.E.

Mar del Plata

Taller; 2do. Taller de Órganos Artificiales, Biomateriales e Ingeniería de Tejidos; 2011

Facultad de Ingeniería de la UNMdP. INTEMA (UNMdP-CONICET). SLABO.

BAL devices were designed to ?bridge? patients until they either recover or receive a liver transplant. The first prototype developed in our laboratory consisting in a simple hollow fiber-based cartridge with blood flowing through the fibers lumen showed an effective ammonia depuration rate using isolated hepatocytes as the metabolically active component. As the ?ideal? biological component should contain all liver cell types to obtain the maximum response, we became interested in evaluating the performance of LMOs. LMOs are tissue slices that retain the basic microarchitecture of the liver lobe and its physiological characteristics. The use of LMOs is also attractive because it obviates the stages of cell isolation and cultivation. Adapting the cylindrical shaped model used with hepatocytes did not showed the expected results, so the objectives of this work were to develop a BAL model suitable to use LMOs, and evaluate the performance of rat LMOs in this new model. LMOs were manually cut from rat livers into slices of 338±27 ìm thickness, n=25. We constructed a new BAL prototype using a 25 cm2 culture flask, which offers a flat surface that allows a better bathing and shaking of plane LMOs. LMOs were loaded into the BAL and an ammonia overload (1.06±0.12 mM, n=3) was added to the blood before initiating the system perfusion at 9 mL/min. LMOs detoxify 49.3±8.8 % of the initial ammonia overload at 120 min and the LDH release was 6.1±2.2 %, showing a good maintenance of their viability. In conclusion, the new BAL design is adequate for a good performance of LMOs as biological component.