Liver assist devices

Despite these failures, the need still exists for alternative liver therapies. Several new techniques including cell transplantation, tissue-engineered constructs, and extra- and paracorporeal devices seek to relieve some of the demands placed on a compromised liver. Liver assist devices allow the liver to regenerate its function by removing some of the demands. Bridge-to-transplant devices seek to maintain patients until suitable donors are available. Some therapies seek to remove toxins from the blood, and they have a place in the treatment scheme, but due to the complex and multifunctional nature of the organ, some type of cell-based therapy is considered a more complete solution. 

Our proposal is not theoretical. Researchers have used reticulated hydrophobic polyurethanes as liver assist devices with some success. We will discuss this research and future work in detail later. For now, it is useful to present an overview. Matsushita et al. inoculated a reticulated polyurethane with porcine hepatic cells, "fhe device functioned as noted, but it was necessary to separate the plasma from the blood because conventional hydrophobic polyurethanes are not hemocompatible. In addition, the technique made no provision for cell attachment. Workers in our laboratory grafted a hydrophilic polyurethane to the structural members of a hydrophobic reticulated foam in an effort to make the composite hemocompatible. Additionally, this gave us the opportunity to add cell attachment proteins. 

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. 

While these devices represent the leading edge in extracorporeal liver-assist devices, two other projects currently in animal trials deserve some attention as they represent other scaffold types. 

Sussman, N.L., Chong, M.G., Koussayer, T., Da-ER He, Shang, T.A., Whisennand, H.H., Kelly, XH. Reversal of fulminant hepatic failure using an extracorporeal liver assist device. Hepatology 1992 16 60-65... 

Hollow Fiber Entrapped Microsomes as a Liver Assist Device in Drug Overdose Treatment... 

Stably immobilized 3D flat aggregates and exhibited superior cell bioactivity with higher levels of liver-specific function maintenance in terms of albumin secretion, urea synthesis and cytochrome P-450 enzyme than 3D spheroid aggregates formed on GC films. These results suggested that the GC-based nanofibrous scaffolds could be useful for various applications such as bioartificial liver-assist devices and tissue engineering for liver regeneration as primary hepatocytes culture substrates. 

Microfabrication enables the creation of complex tissue-engineered products that can be used to replace or augment failing organs and tissues. The number and variety of microfabricated tissue-engineered products have increased rapidly in the last several years microporous biocapsules to provide immunological protection to pancreatic islets micropattemed hepatocytes and mesenchymal cells as key components of liver assist devices microtextures basement-membrane-type structures to create skin with proper surface texture and microspatial control of the distribution of vitronection or other extracellular matrix proteins to promote the formation of mineralized bone-like tissue in vivo (Bhatia and Chen, 1999). 

The bioartificial liver support devices that are under investigation include the extracorporeal liver assist device (ELAD, Vital Therapies, San Diego, Cahfornia, USA) and the HepatAssist Liver Support System (HepaLife Technologies, Boston, Massachusetts, USA). 

FIGURE 80.4 Extracorporeal liver assist device (ELAD) circuit. 

MUhs JM, Cronin DC, Johnson R et al. Initial experience with the modified extracorporeal liver-assist device for patients with fulminant hepatic failure System modifications and chnical impact. Transplantation 2002 74 1735M 6. 

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