A number of membrane bioartificial devices have been proposed for liver support. However, their design does not yet ensure the successful treatment of acute liver insufficiency. In this paper, the Author reviews the limitations of the mass transport phenomena to the performance of a membrane bioartificial liver support device. First of all the requirements that an optimal membrane bioartificial liver support device has to meet for the therapy to be effective are presented. On these grounds, the issues that are still to be addressed to optimize the performance of such devices are discussed: particular attention is devoted to the mass transport phenomena in each region of the membrane bioartificial device. Finally, the main transport features of the membrane bioartificial liver support devices proposed so far are illustrated and examined.
HigginsG.M., AndersonR.M.. Experimental pathology of the liver.Arch Pathol1931; 31: 186–202.
3.
LinT.Y., LeeC.S., ChenC.C., LianK.Y., LinW.S.J.. Regeneration of human liver after hepatic lobectomy studies by repeated liver scanning and repeated needle biopsy.Ann Surg1979; 190: 48–53.
NoseY.. Artificial liver for a bridge to liver transplantation.Artif Organs1989; 13: 415–6.
7.
SorrentinoF.. Prime ricerche per la realizzazione di un fegato artificiale.Chir Patol Sper1956; 4: 1401–14.
8.
SenP.K., BhaleraoR.A., ParulkarG.P., SamsiA.B., ShahB.K., KinareS.G.. Use of perfused cadaveric liver in the management of hepatic failure.Surgery1966; 59: 774–81.
9.
AbounaG.M., CookJ.S., FisherL.M., StillW.J., CostaG., HumeD.M.. Treatment of acute hepatic coma by ex vivo baboon and human liver perfusions.Surgery1972; 71: 537–47.
10.
LieT.S.. Treatment of acute hepatic failure by extracorporeal hemoperfusion over human and baboon liver. In: BrunnerG., SchimdtF.W., eds. Artificial liver support.Berlin: Springer-Verlag, 1981; 268–73.
11.
MitoM.. Hepatic assist: present and future.Artif Organs1986; 10(3): 214–8.
12.
SoyerT., LempinenM., WalkerJ.E., SupanwanidP., EisemanB.. Extracorporeal assist of anhepatic animals with liver slice perfusion.Am J Surg1973; 126: 20–4.
NybergS.L., ShatfordR.A., HuWs. Hepatocyte culture systems for artificial liver support: implications for critical care medicine (bioartificial liver support).Crit Care Med1992; 20(8): 1157–68.
15.
ReidL.M., JeffersonD.M.. Culturing hepatocytes and other differentiated cells.Hepatology1984; 4: 548–59.
16.
SprayD.C., FujitaM., SaezJ.C.. Proteoglycans and glycosaminoglycans induce gap junction synthesis and function in primary liver cultures.J Cell Biol1987; 105: 541–51.
17.
WarrenM., FryJ.R.. Influence of medium composition on 7-alkoxycoumarin O-dealkylase activities of rat hepatocytes in primary maintenance culture.Xenobiotica1988; 18: 973–81.
18.
SussmanN.L.. Chong MG, Koussayer T, et al. Reversal of fulminant hepatic failure using an extracorporeal liver assist device.Hepatology1992; 16: 60–5.
19.
NybergS.L., PlattJ.L., ShirabeK., PayneW.D., HuW-S, CerraF.B.. Immunoprotection of xenocytes in a hollow fiber bioartificial liver.ASAIO J1992; M463–7.
20.
GerlachJ., EnckeJ., NeuhausP.. Hepatocyte culture in bioreactors and the development of extracorporeal hybrid liver support systems.Transplantationsmedizin1993; 6: 1–4.
GerlachJ., KloppelK., SchauweckerH.H., TauberR., MullerC.H., BucherlE.S.. Use of hepatocytes in adesion and suspension cultures for liver support bioreactors.Int J Artif Organs1989; 12: 788–92.
24.
JaureguiH.O., NaikS., DriscollJ.L., SolomonB.A., GallettiP.M.. Adult rat hepatocyte cultures as the cellular component of an artificial hybrid liver. In: PaulJ.P., ed. Biomaterials in artificial organs.Weinheim, Deerfield Beach Fl: VCH, 1985; 130–40.
25.
GerlachJ., KloeppelK., MuellerC.. Hepatocyte aggregate culture technique for bioreactors in hybrid liver support systems.Int J Artif Organs1993; 16(12): 843–6.
26.
DunnJ.C.Y., YarmushM.L., KoebeH.G., TompkinsR.G.. Hepatocyte function and extracellular matrix geometry: long-term culture in a sandwich configuration.FASEB J1989; 3: 174–7.
27.
DunnJ.C.Y., TompkinsR.G., YarmushM.L.. Long-term in vitro function of adult hepatocytes in a collagen sandwich configuration.Biotechnol Prog1991; 7: 237–45.
28.
BucherN.L., RobinsonG.S., FarmerS.R.. Effects of extracellular matrix on hepatocyte growth and gene expression: implications for hepatic regeneration and the repair of liver injury.Semin Liver Dis1990; 10: 11–9.
29.
BaderA., KnopE., BokerK., MannsM., RealeE., PichòmayrR.. Three dimensional co-culture of hepatic sinusoidal cells. In: Knook DL, Wisse E, eds. Cells of the hepatic sinusoid.The Netherlands: AK Leiden,1993; 14: 562–3.
30.
MulterM.. Basic principles of membrane technology.Dordrecht: Kluwer Academic Publishers, 1991.
31.
CatapanoG., Di LorenzoM.C., Delia VolpeC., De BartoloL., FalcoF., MigliaresiC.. Polymeric membranes for cell culture in a hybrid liver support device: effect of membrane morphology on hepatocyte viability and functions (submitted).
32.
GerlachJ., StollP., SchnoyN., BuecherlE.S.B.. Membranes as substrate for hepatocyte adhesion in liver support bioreactors.Int J Artif Organs1990; 13(7): 436–41.
33.
CatapanoG., Di LorenzoM.C., Delia VolpeC., De BartoloL., FalcoF., MigliaresiC.. Membrane polimeriche semipermeabili da adoperarsi come supporto per I'adesione di epatociti isolati in un fegato bioartificiale a membrane.Gnoseis (special Issue)1994; 1(1): 61.
34.
WardR.A., KleinE., HardingG.B., MurchisonK.E.. Response of complement and neutrophils to hydrophilized synthetic membranes.Trans ASAIO1988; 34(3): 334–7.
FoyB.D., LeeJ., MorganJ., TonerM., TompkinsR.G., YarmushM.L.. Optimization of hepatocyte attachment to microcarriers: importance of oxygen.Biotechnol Bioeng1993; 42: 579–88.
37.
CatapanoG., De BartoloL., LombardiC.P., DrioliE.. The effect of oxygen transport resistances on the viability and functions of isolated rat hepatocytes.Int J Artif Organs this issue.
38.
WoelfleD., JungermannK.. Long-term effects of physiological oxygen concentrations on glycolysis and gluconeogenesis in hepatocyte cultures.Eur J Biochem1985; 151: 299–303.
NybergS.L., ShatfordR.A., PeshwaM.V., WhiteJ.G., CerraF.B., HuW.S.. Evaluation of a hepatocyte-entrapment hollow fiber bioreactor: a potential bioartificial liver.Biotechnol Bioeng1993; 41: 194–203.
42.
GlackenM.W., FleischakerR.J., SinskeyA.J.. Reduction of waste product excretion via nutrient control: possible strategies for maximizing product and cell yields on serum in cultures of mammalian cells.Biotechnol Bioeng1986; 28: 1376–89.
43.
PiretJ.M., DevensD.A., CooneyC.L.. Nutrient and metabolite gradients in mammalian cell hollow fiber bioreactors.Canad J Chem Eng1991; 69: 421–8.
44.
CatapanoG., De BartoloL.. The effect of catabolites concentration on the viability and functions of isolated rat hepatocytes (submitted).
45.
MarchD.C., HjelmhaugP.K., VreugdenhilP.K.. Hypothermic preservation of hepatocytes. III. Effects of resuspension media on viability after up to 7 days of storage.Hepatology1991; 13(3): 500–8.
46.
BerryM.N., EdwardsA.M., BarrittG.J.. Isolated hepatocytes preparation, properties and application. In: Burdon RH, van Knippenberg PH, eds. Laboratory techniques in biochemistry and molecular biology.Amsterdam-New York-Oxford: Elsevier,1991; 21: 265–353.
47.
MiddlemanS.. Cardiovascular transport phenomena.New York: Wiley-Interscience,1972.
48.
WhitmoreR.L.. Rheology of the circulation.Oxford: Pergamon Press, 1968.
49.
WickramasingheS.R.E., SemmensM.J., CusslerE.L.. Mass transfer in various hollow fiber geometries.J Membrane Sci1992; 69: 235–50.
50.
CatapanoG., BerginsM., PapenfussH.D., RintelenT., BaurmeisterU.. Mass and momentum transport in cross-wound hollow fiber devices with extra-luminal flow (ELF). International Congress on Membrane (ICOM) ‘90. Chicago, IL (USA): August 20–24, 1990.
KleinE., HollandF.F., EberleK.. Comparison of experimental and calculated permeability and rejection coefficients for hemodialysis membranes.J Membrane Sci1979; 5: 173–88.
ChresandT.J., GilliesR.J., DaleB.E.. Optimum fiber spacing in a hollow fiber bioreactor.Biotechnol Bioeng1988; 32: 983–92.
55.
PillarellaM.R., ZidneyA.. Effect of beta cell distribution on the performance of a bioartificial pancreas.Trans ASAIO1990; 36: M715–9.
56.
ToddD.G., MoscioniA.D., RozgaJ., DemetriouA.A.. Mass transfer in a hollow fiber device used as a bioartificial liver.ASAIO J1993; 886–92.
57.
CatapanoG., lorioG., DrioliE.. Theoretical and experimental analysis of a hybrid bioartificial membrane pancreas: a distributed parameter model taking into account Starling fluxes.J Membrane Sci1990; 52: 351–78.
58.
SatterfieldC.N.. Mass transfer in heterogeneous catalysis.Florida: RE Krieger, 1980.
59.
RonyP.R.. Biotechnol Bioeng1971; 13: 431–47.
60.
SunA.M., ParisiusW., HealyG.M., VacekI., MacmorineH.G.. The use in diabetic rats and monkeys, of artificial capillary units containing cultured islets of Langerhans (artificial endocrine pancreas).Diabetes1977; 26(12): 1136.
61.
KnazekR.A., GullinoP.M., KohlerP.O., DedrickR.L.. Cell culture on artificial capillaries: an approach to issue growth in vitro.Science1972; 178: 65–7.
