Liver, artificial

Current Clinical Activity in Scaffold-Based Artificial Liver Development... 

Jauregui, H., Hayner. N.. Solomon, B., and GaUetti, P. Hybrid Artificial Liver, in Biocompatible Polymers. Metals, and Composites. Szycher, M., Ed., Technomics Publishing, Lancaster. PA, 1983, chap. 39. 

Tomonobu, G., Shimada, M., Shirabe, K., Nakazawa, K.. Ijima, H., Matsushita, T., Funatsu, K., Sugimachi, K., Evaluation of a Hybrid Artificial Liver Using a Polyurethane Foam Packed-Bed Culture System in Dogs, Journal of Surgical Research 82, 131-136 (1999). 

Yarmush, M., Dunn, J., and Tompkins, R. Assessment of artificial liver support technology. Cell Transplant. 1,323,1992. 

Funatsu, K., Ijima, H, et al. Hybrid artificial liver using hepatocytes organoid culture. Artificial Organ 25(3) 194-200, 2001. 

Wake, M.C., Patrick, C.W and Mikos, A.G., Pore morphology effects on the fibrovas-cular tissue growth in porous polymer substrates. Cell Transplant. 3, 339,1994. Gion, T, Shimada, M., Shirada M., et al. Evaluation of a hybrid artificial liver using a polyurethane foam packed-bed culture system in dogs. Journal of Surgical Research 82, 132-136 1999. 

Gion, T., Shimada, M.. Shirada M., et al. Evaluation of a hybrid artificial liver using... 

This study was reported with another set of experiments that confirmed the growth of fibroblasts in connection with an experimental bum dressing. " While our work was positive enough to warrant further research, a technical problem prevented continued work. While we felt the surface chemistry was a necessary component of a successful artificial liver, it was not sufficient. In order to build a successful device, fluids must be able to enter and exit the environment freely. We discussed the differences in structure between open-celled polyurethanes and reticulated foam earlier. 

Around that time, Taku Matsushita and coworkers began work on the use of conventional polyurethane foams (we used hydrophilic polyurethanes) as scaffolds for the propagation of hepatic cells. Using a rat rnodel, they were able to demonstrate the development of the hepatic spheroids necessary in the development of a functional artificial liver. 

The success of Matsushita s method and the encouraging developments in our laborabory set the stage for a decade of independent research into what we see as the best technology for the development of a liver-assist device. In a sense, Matsushita s work confirmed the structure of the device and our work confirmed the chemistry of the surface. Matsushita continued his work without the benefit of our technology and has successfully demonstrated the use of his device in a dog model. In a 1999 report, an artificial liver was reported to be equal, and probably superior to the most successful hollow-fiber device. 

Yang et al. discussed the basic properties of an implantable or extracorporeal artificial liver. The article focused on implantable devices but other than biodegradability, the properties of implantable devices are also applicable to extracorporeal devices. The focus of the article on implantable devices reveals an unfortunate prejudice on the part of much of the scientific community. Most researchers in this field are working on devices intended to be placed in the body. 

CURRENT CLINICAL ACTIVITY IN SCAFFOLD-BASED ARTIFICIAL LIVER DEVELOPMENT... 

FIGURE 7.2 HepatAssist hollow fiber-based artificial liver (Circe Biomedical, Lexington, MA). 

This chapter will focus on three types of membrane extracorporeal devices, hemodialyzers, plasma filters for fractionating blood components, and artificial liver systems. These applications share the same physical principles of mass transfer by diffusion and convection across a microfiltration or ultrafiltration membrane (Figure 18.1). A considerable amount of research and development has been undertaken by membrane and modules manufacturers for producing more biocompatible and permeable membranes, while improving modules performance by optimizing their internal fluid mechanics and their geometry. 

Figure 18.11 Generic representation of combined filtration and adsorption columns systems for artificial liver support.

Artificial liver support systems aim at the extracorporeal removal of water soluble and protein-bound toxins (albumin being the preferential binding protein) associated with hepatic failure. Albumin contains reversible binding sites for substances such as fatty acids, hormones, enzymes, dyes, trace metals and drugs [26] and therefore helps elimination by kidneys of substances that are toxic in the unbound state. It should be noticed that the range of substances to be removed is broad and not completely identified. Clinical studies showed that the critical issue of the clinical syndrome in liver failure is the accumulation of toxins not cleared by the failing liver. Based on this hypothesis, the removal of lipophilic, albumin-bound substances, such as bilirubin, bile adds, metabolites of aromatic amino acids, medium-chain fatty acids, and cytokines, should be benefidal to the dinical course of a patient in liver failure. 

It seems, nevertheless, dear that the combination of membrane-based and adsorbent techniques, perhaps in addition to bioartifidal systems, present a potential supply to help the patient waiting for a graft or even for tissue regeneration. In the biomedical field, the extension of techniques previously developed for other topics, such as biochromatography for instance, has always proved to be promising. This could hopefully be the case for artificial liver support. 

On the commercial front, an artificial liver system has reached advanced clinical trial stage. Based on pig hep-atocytes immobilized in a hollow-fiber membrane module, this system provides temporary life support until a liver from a human donor is available for transplantation (Fig. 50). Also under development is an artificial pancreas intended as a permanent replacement of the native organ (Fig. 51). 

The so-called artificial liver system was first developed by K. N. Matsumura et at (1978). This procedure comprised haemodialysis across a suspension of vital hepatocytes. Such semi-artificial liver was first used clinically in 1987 on a patient with bile-duct carcinoma and acute liver failure (K.N. Matsumura et at). 

It is no longer too bold to pin legitimate hopes on the development of an artificial liver. The preliminary objective hereby must be to replace the most important liver functions for a longer period of time, thus affording the diseased liver of the patient a greater chance to regenerate. 

Dowling, D.J., Mutimer, D.J. Artificial liver support in acute liver failure. Eur. X Gastroenterol. Hepatol. 1999 11 991-996... 

Chang, T.M.S. Artificial Liver and Artifical Cells Plenum Press New York, 1978. 

Ijima H, Matsushita T, Nakazawa N, Koyama S, Gion T, Shirabe K, Shimada M, Takenaka K, Sugimachi K Funatsu K (1997) Spheroid formation of primary dog hepatocytes using polyurethane foam and its application to hybrid artificial liver. In Carrondo KJT (eds) Animal Cell Technology, pp. 577-583. 

Yanagi, K. Ookawa, K. Mizuno, S. Ohshima, N. Performance of a new hybrid artificial liver support system using hepatocytes entrapped within a hydrogel. ASAIO Trans. 1989, 35 (3), 570-572. 

Liver. The liver performs a wide variety of chemical reactions in the body and is the main locus of detoxification. Successful liver transplantation is somewhat rare, and no true artificial liver seems likely in the near future. The process of hemoperfusion, which is sometimes termed an artificial liver, can be used to supplement or relieve the normal liver functions for short time periods. In this technique, the patient s blood is passed through a column or bed of some sorbent material that removes toxic chemicals from the blood. This technique is often used in cases of drug overdose, poisoning, and acute hepatitis. The sorbent material can be charcoal, ion-exchange resins, immobilized hepatic material, or liver material enclosed in artificial cells (microcapsules, usually made from a polyamide). The column is usually a plastic material, and plastic tubing is used to direct the blood flow to and from the device ( 1, 57, M). 

Chang, T. M. S. "Artificial Kidney, Artificial Liver and Artificial Cells" Plenum New York, 1978. 

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