In vitro analysis of a hepatic device with intrinsic microvascular-based channels
A novel microfluidics-based bilayer device with a discrete parenchymal chamber modeled upon hepatic organ architecture is described. The microfluidics network was designed using computational models to provide appropriate flow behavior based on physiological data from human microvasculature. Patterned silicon wafer molds were used to generate films with the vascular-based microfluidics network design and parenchymal chamber by soft lithography. The assembled device harbors hepatocytes behind a nanoporous membrane that permits transport of metabolites and small proteins while protecting them from the effects of shear stress. The device can sustain both human hepatoma cells and primary rat hepatocytes by continuous in vitro perfusion of medium, allowing proliferation and maintaining hepatic functions such as serum protein synthesis and metabolism. The design and fabrication processes are scalable, enabling the device concept to serve as both a platform technology for drug discovery and toxicity, and for the continuing development of an improved liver-assist device.
KeywordsTissue engineering Hepatocytes Liver Microfabrication
Support from the Center for Integration of Medicine and Innovative Technology (US Army DAMD17-02-2-0006) is gratefully acknowledged. We thank Dr. Irina Pomerantseva for critically reading of the manuscript.
- J.E. Coligan (ed.), Current protocols in protein science (John Wiley & Sons Inc., Brooklyn, N.Y., 1996)Google Scholar
- M.F. Kiani, A.R. Pries, L.L. Hsu, I.H. Sarelius, G.R. Cokelet, Am. J. Physiol. 266(5 Pt 2), H1822–H1828 (1994)Google Scholar
- A.R. Pries, D. Neuhaus, P. Gaehtgens, Am. J. Physiol. 263(6 Pt 2), H1770–H1778 (1992)Google Scholar
- UNOS, Annual Report of the U.S. Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients: Transplant Data 1994–2006 (Department of Health and Human Services, Health Resources and Services Administration, Healthcare Systems Bureau, Division of Transplantation, Rockville, MD, 2007)Google Scholar
- E.J. Weinberg, J.T. Borenstein, M.R.O. Kaazempur-Mofrad, B.J.P. Vacanti, MRS Symp. Proc. 820, 126–127 (2004)Google Scholar