In vitro evaluation of a novel bioreactor based on an integral oxygenator and a spirally wound nonwoven polyester matrix for hepatocyte culture as small aggregates

Abstract

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Present and Future Developments in Hepatic Tissue Engineering for Liver Support Systems

“…In this context, our studies have shown that in vivo-like quantitative as well as qualitative performance could be achieved in vitro using pharmaceutical drugs as test candidates (Bader et al 1992(Bader et al , 1996(Bader et al , 1998Langsch and Bader 2001). Currently, rat and human hepatocytes are being successfully cultured on novel modified polyetheretherketone membranes Nyberg et al (1992aNyberg et al ( , c, 1993Nyberg et al ( , 1996Nyberg et al ( , 1999 Pig Immunoisolation pig, rabbit, rat Jauregui et al (1994Jauregui et al ( , 1995 Protection against viral infection in humans by xenogeneic cells Gerlach (1996) In vivo-like microenvironment Ellis et al (1996) Protection from shear stress Flendrig et al (1997Flendrig et al ( , 1999 Ease of scale-up (PEEK-WC and PEEK-WE-polyurethane) which have been proposed to be promising biomaterials in liver support systems (De Bartolo et al 2004). The use of a flat membrane bioreactor as an extracorporeal liver support system, however, is accompanied by some disadvantages, such as the potential large dead volume and the low surface area-to volume ratio, as well as providing limited protection against viral infection by xenogeneic cells (depending on the molecular weight cut-off of the membranes used).…”

“…To meet hepatocyte demands on their environment and their need for oxygen, a bioreactor incorporating design concepts of a hollow fiber oxygenator (OXY-HFB) was built (Jasmund et al 2002). Alternatively, a bioreactor has been constructed that consists of a spirally wound, nonwoven polyester matrix in a cartridge for hepatocyte immobilization and aggregation, and of integrated hollow fibers for low metabolite gradients, decentralized oxygenation, and CO 2 removal (Flendrig et al 1997). Medium or plasma is in direct contact with the hepatocytes by perfusion through semipermeable membranes.…”

“…In contrast, flat membrane plates covered with a cryoprotective solution are completely cryopreservable (unpublished observation). All techniques discussed in this article have advantages in the large scale bioreactors for liver support systems due to their easy upscaling (Gerlach et al 1993;Flendrig et al 1997;De Bartolo and Bader 2001;Sauer et al 2001). Systems using hepatic spheroids and encapsulated hepatocytes can easily be scaled to the cell mass needed to sustain the patient's life but may be associated with the possible dead volume and limitations of the mass transfer.…”

Intracellular nucleotide pools and ratios as tools for monitoring dedifferentiation of primary porcine hepatocytes in culture

“…Cell adhesion to matrix scaffolds is necessary for cells to metabolize, survive or proliferate (Boudreau et al 1995;Fang et al 1996;Frisch and Francis 1994;Meredith et al 1993;Re et al 1994;Zhu et al 1996). A large number of liver cell culture techniques have been developed to promote cell organization with the aim of providing conditions similar to in vivo conditions Cultivation on microcarriers (Demetriou et al 1986), in the extra-capillary space of a multibundle hollow fibre membrane network (Gerlach et al 1994), within a non-woven fabric mesh (Flendrig et al 1997), co-culture with non-parenchymal cells in an extracellular matrix environment (Bucher et al 1990;Bader et al 1995;Yagi et al 1998;Tilles et al 2001), cultivation of primary hepatocytes in spheroids (Tobe et al 1992;Kobayashi et al 1994) or use of the so-called sandwich model (Dunn et al 1989; have been reported to improve organization similar to the micro-architecture of hepatocyte monolayers found in vivo and of extending the presence of differentiation markers.…”

Cryopreservation of Hepatocytes for Bioartificial Liver Devices

“…Due to the risk of inter-species transfer of viruses, xenotransplantation is generally unacceptable, particularly where the engineered tissue is to be transplanted into the body (Blusch et al, 2002). However, replacement of organ function with extracorporeal devices has lead to the development of BAL devices containing primary porcine cells (Demetriou, 1998;Flendrig et al, 1997;Gerlach et al, 1996;Watanabe et al, 1997). Cryopreservation is the only practical option for maintaining a stock or bank of hepatocytes for clinical use, either in a BAL or for transplantation.…”