Optimized performance of the integrated hepatic cell-loaded cryogel-based bioreactor with intermittent perfusion of acute liver failure plasma.

Abstract

Acute liver failure (ALF) plasma has cytotoxic effects on the cell-loaded bioreactor in bioartificial liver support systems due to the presence of innumerable hepatotoxic compounds that adversely affect the morphology and functionality of the cells. We have designed a hybrid bioreactor that integrates a hepatic cell-loaded cryogel disc and an activated carbon cloth in one compact unit, with potential application as a bioartificial liver support. In this article, we assess the performance of this integrated hybrid cryogel-based bioreactor in a perfusion-based culture system and analyze its functionality and longevity in the presence of intermittent exposure to ALF plasma. The bioreactor maintained functionality in terms of glucose consumption and albumin synthesis for up to 40 days under perfusion. Additionally, intermittent perfusion of plasma from rodent models of ALF resulted in a decrease in viability and functionality only after the second spike of plasma, with the bioreactor maintaining its functionality even after the first spike. Similar results were obtained with patient plasma indicating the potential to reuse the bioreactor for multiple sessions of liver dialysis. Collectively, these results suggest the potential of the integrated cryogel-based bioreactor to be used at most twice before being disposed of. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 259-269, 2018.