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Radial flow hepatocyte bioreactor using stacked microfabricated grooved substrates
Author(s) -
Park Jaesung,
Li Yawen,
Berthiaume François,
Toner Mehmet,
Yarmush Martin L.,
Tilles Arno W.
Publication year - 2007
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.21572
Subject(s) - bioreactor , bioartificial liver device , substrate (aquarium) , materials science , biomedical engineering , hepatocyte , shear stress , chemistry , biophysics , composite material , biochemistry , biology , medicine , ecology , organic chemistry , in vitro
Abstract Bioartificial liver (BAL) devices with fully functioning hepatocytes have the potential to provide temporary hepatic support for patients with liver failure. The goal of this study was to optimize the flow environment for the cultured hepatocytes in a stacked substrate, radial flow bioreactor. Photolithographic techniques were used to microfabricate concentric grooves onto the underlying glass substrates. The microgrooves served to protect the seeded hepatocytes from the high shear stresses caused by the volumetric flow rates necessary for adequate convective oxygen delivery. Finite element analysis was used to analyze the shear stresses and oxygen concentrations in the bioreactor. By employing high volumetric flow rates, sufficient oxygen supply to the hepatocytes was possible without an integrated oxygen permeable membrane. To implement this concept, 18 microgrooved glass substrates, seeded with rat hepatocytes cocultured with 3T3‐J2 fibroblasts, were stacked in the bioreactor, creating a channel height of 100 µm between each substrate. In this bioreactor configuration, liver‐specific functions (i.e., albumin and urea synthesis rates) of the hepatocytes remained stable over 5 days of perfusion, and were significantly increased compared to those in the radial flow bioreactor with stacked substrates without microgrooves. This study suggests that this radial flow bioreactor with stacked microgrooved substrates is scalable and may have potential as a BAL device in the treatment of liver failure. Biotechnol. Bioeng. 2008;99: 455–467. © 2007 Wiley Periodicals, Inc.