Hollow fiber bioartificial liver

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

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). 

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]. 

The so-called UCLA bioartificial liver involves the direct hemoperfusion of microencapsulated porcine hepatocytes in an extracorporeal chamber (Eigure 7.3). Since it permits perfusion with whole blood, it has an advantage over the hollow fiber technique that has to be perfused with plasma. The hepatocytes are isolated from pig livers and microencapsulated in an alginate-polylysine membrane. Microencapsulated hepatocytes are approximately 300 to 700 pm in diameter. 

In order to sustain life, a bioartificial liver device should contain at least 10-30% of the normal liver mass (i.e., 150-450 g of cells in the case of an adult). In a bioartificial liver device, the animal or human liver cells can conceivably be cultured and used in several forms, including (i) independent single-cell suspensions (ii) spheroid (i.e., globular) aggregates of cells of 100-150 pm diameter (iii) cylindroid, rod-like aggregates of cells of 100-150 pm diameter (iv) encapsulated cells and (v) cells attached to solid surfaces, such as microcarriers, flat surfaces, and the inside or outside of hollow fibers. In order to facilitate mass transfer, a direct contact between the cells and the blood seems preferable. Among the various types of bioartificial liver device tested to date, four distinct groups can be identified [19] ... 

Below, we will refer to two typical cases of MBR application in artificial organ engineering the bioartificial kidney and bioartifidal liver. It should be noted that the clinical impact of the artifidal kidney and liver is quite different. The artificial kidney, in its hollow-fiber modules form, is the most employed hemopurification device. The therapy for chronic renal failure concerns hundreds of thousands of patients all over the dvilized world, making the artificial kidney one of the most diffused biomedical devices on... 

Bioartificial hollow-fiber liver devices have cultured liver cells (hepatocytes) growing in between hollow fibers. The patient s blood is passed through the fibers, where it diffuses into the extra-fiber spaces, interacts with the hepatocytes, and returns to the patient. In laboratory tests, such devices maintained liver function for a few months. 

The potential for artificial livers as extracorporeal support of acute liver failure has been assessed (30). The development of a hollow fiber bioreactor, where hepatocytes were entr ped in a collagen gel was found to be effective after five days based on hepatocyte viability, oxygen uptake, and sustained albumin activities. The application of polymer dhemistry to the development of bioartificial wgans has been recently reviewed and an evaluation of the polymer structure/biomatoial fimetion relation ip made concerning an artificial pancreas (31). 

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