Use of Micropathways to Improve Oxygen Transport in a Hepatic System

[+] Author and Article Information
Randall E. McClelland, Robin N. Coger

Department of Mechanical Engineering & Engineering Science, University of North Carolina—Charlotte, 9201 University City Blvd., Charlotte, NC 28223-0001

J Biomech Eng 122(3), 268-273 (Feb 06, 2000) (6 pages) doi:10.1115/1.429657 History: Received October 21, 1999; Revised February 06, 2000
Copyright © 2000 by ASME
Your Session has timed out. Please sign back in to continue.


Campra, J. L., and Reynolds, T. B., 1988, “The Hepatic Circulation,” in: The Liver Biology and Pathobiology, M. Arias and H. Popper, et al., eds., Raven, New York, pp. 911–930.
Berne, R., and Levy, N., 1998, Physiology, Mosby, MO, pp. 3–20, 567–568.
Macdonald, J. M., Griffin, J., Kubota, H., Griffith, L., Fair, J., and Reid, L. M., 1999, “Bioartificial Livers,” in: Cell Encapsulation Technology and Therapeutics, W. Kuhtreiber, R. P. Lanza, and W. L. Chick, eds., Birkhauser, Boston, MA (in press).
Tharakan,  J. P., and Chau,  P. C., 1985, “A Radial Flow Hollow Fiber Bioreactor for the Large-Scale Culture of Mammalian Cells,” Biotechnol. Bioeng., XVIII, pp. 329–342.
Gerlach,  J., Kloppel,  K., Stoll,  P., Vienken,  J., and Muller,  C., 1990, “Gas Supply Across Membranes in Bioreactors for Hepatocytes Culture,” Artif. Organs, 14, No. 5, pp. 328–333.
Catapano,  G., De Bartolo,  L., Lombardi,  C. P., and Drioli,  E., 1996, “The Effect of Oxygen Transport Resistances on the Viability and Functions of Isolated Rat Hepatocytes,” Int. J. Artif. Organs, 19, No. 1, pp. 61–71.
Nyberg,  S. L., Shatford,  R. A., Peshwa,  M. V., White,  J. G., Cerra,  F. B., and Hu,  W. S., 1992, “Evaluation of a Hepatocyte-Entrapment Hollow Fiber Bioreactor: A Potential Bioartificial Liver,” Biotechnol. Bioeng., 41, pp. 194–203.
Dixit,  V., and Gitnick,  G., 1996, “Artificial Liver Support: State of the Art,” Scand. J. Gastroenterol., 31, Suppl. 220, pp. 101–114.
Piret,  J. M., Devens,  D. A., and Cooney,  C. L., 1991, “Nutrient and Metabolite Gradients in Mammalian Cell Hollow Fiber Bioreactors,” Can. J. Chem. Eng., 69, pp. 421–428.
Ijima,  H., Matsushita,  T., Nakazawa,  K., Fujii,  Y., and Funatsu,  K., 1998, “Hepatocyte Spheroids in Polyurethane Foams: Functional Analysis and Application for a Hybrid Artificial Liver,” Tissue Eng., 4, No. 2, pp. 213–226.
Demetriou,  A. A., Watanabe,  F., Rozga,  J., Podsta,  L., Lepage,  E., Morsiani,  E., Moscioni,  A. D., Hoffman,  A., McGrath,  M., Kong,  L., , 1995, “Early Clinical Experience With a Hybrid Bioartificial Liver,” Scand. J. Gastroenterol. Suppl., 208, pp. 111–117.
Davis,  M. W., and Vacanti,  J. P., 1995, “Toward Development of an Implantable Tissue Engineered Liver,” Biomaterials, 17, pp. 365–372.
Glacken,  M. W., Fleischaker,  R. J., and Sinskey,  A. J., 1983, “Large-Scale Production of Mammalian Cells and Their Products: Engineering Principles and Barriers to Scale-Up,” Ann. N.Y. Acad. Sci., 413, pp. 355–372.
Smith,  M. D., Smirthwaite,  A. D., Cairns,  D. E., Cousins,  R. B., and Gaylor,  J. D., 1996, “Techniques for Measurement of Oxygen Consumption Rates of Hepatocytes During Attachment and Post-Attachment,” Int. J. Artif. Organs, 19, pp. 36–44.
Yaegashi,  K., Itoh,  T., Kosaka,  T., Fukushima,  H., and Morimoto,  T., 1996, “Diffusivity of Oxygen in Microvascular Beds as Determined From Po2 Distribution Maps,” Am. J. Physiol., 270, pp. H1390–H1397.
Dunn,  J. C. Y., Tompkins,  R. G., and Yarmush,  M. L., 1991, “Long-Term in Vitro Function of Adult Hepatocytes in a Collagen Sandwich Configuration,” Biotechnol. Prog., 7, No. 3, pp. 237–245.
Seglen,  P. O., 1976, “Preparation of Isolated Rat Liver Cells,” Methods Cell Biol., 13, p. 29.
Lide, D. R., ed., 1997, Handbook of Chemistry and Physics, 78th ed., CRC, Boca Raton, FL.
Bejan, A., 1998, Convective Heat Transfer, 2nd ed., Wiley, New York, pp. 475–479.
Mills, A. F., 1999, Basic Heat and Mass Transfer, Prentice Hall, Inc., Upper Saddle River, NJ, pp. 754–776.
Dunn,  J. C. Y., Yarmush,  M. L., Koebe,  H. G., and Tompkins,  R. G., 1989, “Hepatocyte Function and Extracellular Matrix Geometry: Long-Term Culture in a Sandwich Configuration,” FASEB J., 3, pp. 174–177.
Ezzell,  R. M., Toner,  M., Hendricks,  K., Dunn,  J. C. Y., Tompkins,  R. G., and Yarmush,  M. L., 1993, “Effect of Collagen Gel Configuration on the Cytoskeleton in Cultured Rat Hepatocytes,” Exp. Cell Res., 208, pp. 442–452.
Foy,  B. D., Rotem,  A., Toner,  M., Tompkins,  R. G., and Yarmush,  M. L., 1994, “A Device to Measure the Oxygen Uptake Rate of Attached Cells: Importance in Bioartificial Organ Design,” Cell Transplant, 3, No. 6, pp. 515–527.


Grahic Jump Location
Schematic of oxygen transport in the control system (a) and the “modified” double-walled collagen configuration (b, c). Collagen layers (gray sections) sandwich the hepatocytes, and the cell medium is placed on top (wavy lines). As indicated, the main direction of O2 flow (arrows) is through the medium in the control system (a), and radially outward from the central tube in the “modified” configuration (b, c). A top view of the “modified” configuration is shown in Fig. 1(c).
Grahic Jump Location
Schematic of the cellular oxygen assay used to sustain hepatocytes in the double wall configuration. A nonpermeable container encapsulates the modified double-wall cultures, such that pressurized O2 reaches the cells by diffusing through the central tube (Fig. 1(b)). To ensure suitable CO2 levels, a perfusion system circulates cell medium percolated with CO2, across the surface of the culture.
Grahic Jump Location
Reverse polarity micrographs of O2 transport in normal (A, B) and enhanced (C, D) collagen gels using fluorescent oxygen quenching dye particles
Grahic Jump Location
Schematic of the radial distance from the O2 source within which viable hepatocytes can be sustained for the “modified” (gray) and “modified enhanced” (gray & white) configurations
Grahic Jump Location
Albumin secretion rate of the collagen system control as compared to literature results
Grahic Jump Location
A comparison of albumin secretions between the functional control, the “modified,” “enhanced modified,” and “enhanced modified double-wall” configurations
Grahic Jump Location
Comparison of urea concentration levels of the functional control, the “modified,” “enhanced modified,” and “enhanced modified double-wall” configurations
Grahic Jump Location
Normalized albumin secretion rates of the functional control, the “modified,” “enhanced modified,” and “enhanced modified double-wall” configurations



Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging and repositioning the boxes below.

Related Journal Articles
Related eBook Content
Topic Collections

Sorry! You do not have access to this content. For assistance or to subscribe, please contact us:

  • TELEPHONE: 1-800-843-2763 (Toll-free in the USA)
  • EMAIL: asmedigitalcollection@asme.org
Sign In