Establishing suitable oxygen transport pathways within bioartificial liver replacement devices continues to be an important engineering challenge. Oxygen delivery is critical since this is one of the nutrients necessary to maintain hepatocyte viability and function. In the current study, the microporosity of a collagen extracellular matrix has been modified to permit both diffusion and convection mass transport. Using fluorescent visualization, the enhancement technique was found to extend the oxygen transport distance from 170 μm to 360 μm. Furthermore, in hepatocyte culture studies, the enhancement technique was observed to yield a sixfold increase in the amount of viable hepatocytes able to be sustained by a single O2 source. Normalized function studies confirm that hepatocyte function was also improved in the enhanced collagen configurations. [S0148-0731(00)00903-1]

1.
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.
2.
Berne, R., and Levy, N., 1998, Physiology, Mosby, MO, pp. 3–20, 567–568.
3.
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).
4.
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
.
5.
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
.
6.
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
.
7.
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
.
8.
Dixit
,
V.
, and
Gitnick
,
G.
,
1996
, “
Artificial Liver Support: State of the Art
,”
Scand. J. Gastroenterol.
,
31
, Suppl. 220, pp.
101
114
.
9.
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
.
10.
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
.
11.
Demetriou
,
A. A.
,
Watanabe
,
F.
,
Rozga
,
J.
,
Podsta
,
L.
,
Lepage
,
E.
,
Morsiani
,
E.
,
Moscioni
,
A. D.
,
Hoffman
,
A.
,
McGrath
,
M.
,
Kong
,
L.
, et al.
,
1995
, “
Early Clinical Experience With a Hybrid Bioartificial Liver
,”
Scand. J. Gastroenterol. Suppl.
,
208
, pp.
111
117
.
12.
Davis
,
M. W.
, and
Vacanti
,
J. P.
,
1995
, “
Toward Development of an Implantable Tissue Engineered Liver
,”
Biomaterials
,
17
, pp.
365
372
.
13.
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
.
14.
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
.
15.
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
H1390–H1397
.
16.
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
.
17.
Seglen
,
P. O.
,
1976
, “
Preparation of Isolated Rat Liver Cells
,”
Methods Cell Biol.
,
13
, p.
29
29
.
18.
Lide, D. R., ed., 1997, Handbook of Chemistry and Physics, 78th ed., CRC, Boca Raton, FL.
19.
Bejan, A., 1998, Convective Heat Transfer, 2nd ed., Wiley, New York, pp. 475–479.
20.
Mills, A. F., 1999, Basic Heat and Mass Transfer, Prentice Hall, Inc., Upper Saddle River, NJ, pp. 754–776.
21.
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
.
22.
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
.
23.
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
.
You do not currently have access to this content.