Bioartificial

Sakai, S., Ono, T., Ijima, H. and Kawakami, K. (2001) Synthesis and transport characterization of alginate/ aminopropylsilicate/alginate microcapsule application to bioartificial pancreas. Biomaterials, 22, 2827-2834. 

Teramura Y, Iwata H (2010) Bioartificial pancreas microencapsulation and conformal coating of islet of Langerhans. Adv Drug Deliv Rev 62 827-840... 

Steps 7-10 involved the selection of animal models, islet isolation and the testing of the polymer microcapsules as bioartificial organs. This has been discussed elsewhere [61,62]. 

Maki T, Monaco AP, Million CJP, Solomon BA (1997) In Prokop A, Hunkeler D, Cher-rington A (eds) Bioartificial organs. New York Academy of Sciences, New York, NY... 

Keywords Bioartificial pancreas, biomaterials, complex coacervation, immunoisolation, microencapsulation, polyelectrolytes, water soluble polymers... 

The principle of a bioartificial pancreas design is presented in figure 11. 

Figure 11. Scheme of a bioartificial pancreas surrounded by a hydrogel membrane [266], Some methods used for artificial organs design are presented in table 17. 

Bioreactor Developments for Tissue Engineering Applications by the Example of the Bioartificial Liver... 

Keywords. Bioartificial liver, cell culture, hollow fiber bioreactor, flat membrane bioreactor, spheroids... 

There have already been clinical trials of porcine hepatocyte-based bioartificial livers [5, 6]. However, we believe these systems to represent temporary and short-lived approaches. Compelling evidence from recent experiments show that primary porcine liver cells express and release endogenous retroviral particles that are able to infect human cells. However, long term in vivo investigations of patients previously exposed to porcine tissues over a period of 12 year did not show any porcine endogenous retrovirus (PERV) viremia [7]. Therefore, we consider the further pursuit of porcine bioartificial livers the only solution at present with regard to the cell source. However, as an intermediate term alternative human cell sources are in development [8]. Expansion technologies for human fetal cells may contribute to resolve these limitations in the future. 

Hepatocyte-based bioartificial livers will have two major uses to provide a) short term support for liver-failure patients in the clinic and b) a tool for the pharmaceutical industry to produce drug metabolites for subsequent toxicological studies in vitro. 

To be useful to both, clinicians and the pharmaceutical industry, a bioartificial liver will need to maintain a large number of hepatocytes at high cell densities and in a fully differentiated state for prolonged periods of time. Development of such a system has been impeded by three principal problems a) a requirement for large numbers of cells (>25 10 ) b) loss of liver-specific functions in cultured cells (primary and immortalized) c) nutrient and waste product gradients in high density cultures leading to lowered cell viability and impaired function. 

A bioartificial liver will need to maintain a large number of hepatocytes at high cell densities over a prolonged period of time. The metabolic requirements of hepatocytes, particularly the high rates of oxygen consumption, place strin-... 

Lim F, Sun AM. Microencapsulated islets as bioartificial endocrine pancreas. Science... 

Ng, S.Y., Vandamme, T., Taylor, M.S., and Heller, J. (1997). Controlled drug release from self-catalyzed poly(ortho esters). Bioartificial Organs, 168-178. 

One method of culturing anchorage-dependent tissue cells is to use a bed of packings, on the surface of which the cells grow and through which the culture medium can be passed. Hollow fibers can also be used in this role here, as the medium is passed through either the inside or the outside of the hollow fibers, the cells grow on the other side. These systems have been used to culture liver cells to create a bioartificial liver (Section 15.4.2). 

In recent years, many investigations have been conducted, including clinical trials, with bioartificial fiver devices using either animal or human liver cells. Likewise, many reports have been made with various designs of bioartificial fiver device [19]. However, there are no established fiver support systems that can be used routinely in the same way as hemodialyzers or blood oxygenators. Today, bioartificial fiver devices can be used to assist the fiver functions of patients with fiver failure on only a partial and/or a temporary basis. Moreover, none of these devices can excrete bile, as does the human fiver. 

It should be noted here that the bioartificial fiver device is not only a bioreactor but also a mass transfer device. The mass transfer of various nutrients from the blood into the liver cells, and also the transfer of many products of biochemical reactions from the cells into the bloodstream, should be efficient processes. In human fiver, the oxygen-rich blood is delivered via the hepatic artery, and bioartificial devices should be so designed that the oxygen can be easily delivered to the cells. 

Hollow Fibers. The general configuration of the hollow-fiber apparatus is similar to that of hemodialyzers and blood oxygenators. Hepatocytes or microcarrier-attached hepatocytes are cultured either inside the hollow fibers or in the extra-fiber spaces, and the patient s blood is passed outside or inside the fibers. A bioartificial liver of this type, using 1.5 mm o.d. hollow fibers with 1.5 mm clearance between them, and with tissue-like aggregates of animal hepatocytes cultured in the extra-fiber spaces, can maintain liver functions for a few months [20]. 

Naruse, K., Sakai, Y, Nagashima, I., Jaing, G., Suzuki, M., and Muto, T. Development of a new bioartificial liver module filled with porcine hepatocytes cocultured in a microchannel flat plate bioreactor. Inter. J. art if. Organs 19, 347, 1996. 

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