Premium
Microfabricated grooved substrates as platforms for bioartificial liver reactors
Author(s) -
Park Jaesung,
Berthiaume François,
Toner Mehmet,
Yarmush Martin L.,
Tilles Arno W.
Publication year - 2005
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.20463
Subject(s) - bioreactor , bioartificial liver device , shear stress , substrate (aquarium) , materials science , shear (geology) , composite material , biomedical engineering , hepatocyte , chemistry , biochemistry , medicine , oceanography , organic chemistry , in vitro , geology
An extracorporeal bioartificial liver device has the potential to provide temporary hepatic support for patients with liver failure. Our goal was to optimize the flow environment for the cultured hepatocytes in a flat‐plate bioreactor, specifically focusing on oxygen delivery using high medium flow rates while reducing the detrimental effects of the resulting shear stresses. We used photolithographic techniques to fabricate microgrooves onto the underlying glass substrate. The microgrooves, perpendicular to the axial flow direction, protected the hepatocytes from the shear stress induced by the flowing medium. Using finite element analysis, we found that the velocity gradient change near the cell surface (i.e., bottom of the grooves) was smaller than that near the top surface of the flow channel, indicating that the grooves would provide protection to the attached cells from the mechanical effects of the flowing medium. We also determined that the shear stress at the cell surface could be reduced by as much as 30 times (channel height of 100 μm) in the grooved‐substrate (0.5 dyn/cm 2 ) bioreactor compared to the flat‐substrate (15 dyn/cm 2 ) bioreactor for a medium flow rate of 4.0 mL/min. Albumin and urea synthesis rates of hepatocytes cocultured with 3T3‐J2 fibroblasts remained stable over 5 days of perfusion in the grooved‐substrate bioreactor, whereas in the flat‐substrate bioreactor they decreased over the same time period. These studies indicate that under “high” flow conditions the microgrooved‐substrate in the bioreactor can decrease the detrimental effects of shear stress on the hepatocytes while providing adequate oxygenation, thereby resulting in stable liver‐specific function. © 2005 Wiley Periodicals, Inc.