A mathematical model was developed to predict oxygen transport in a hollow fiber bioartificial liver device. Model parameters were taken from the Hepatix ELAD configuration; a blood perfused hollow fiber cartridge with hepatocytes seeded in the extracapillary space. Cellular oxygen uptake is based on Michaelis-Menten kinetics, and nonlinear oxygen transport in the blood is considered. The effect of modulating three important parameters is investigated, namely, the Michaelis-Menten constants Vm (volumetric oxygen consumption of the hepatocytes) and Km (half-saturation constant), and hollow fiber oxygen permeability. A computer implementation of the model is used to assess whether a given cell mass could be maintained within such a device. The results suggest that liver cell lines possessing low rates of oxygen consumption could be maintained if membranes of sufficiently high oxygen permeability are used. For primary hepatocytes, which have much higher oxygen demands, radial transport of oxygen is rate limiting, and the axial-flow hollow fiber cartridge is thus an inappropriate design for use as a bioartificial liver with primary hepatocytes.
A mathematical model was developed to predict oxygen transport in a hollow fiber bioartificial liver device. The model parameters were taken from the HepatAssist 2000 device, a plasma perfused hollow fiber cartridge with primary hepatocytes seeded in the extracapillary space. Cellular oxygen uptake was based on Michaelis-Menten kinetics. Oxygen transport due to the convective flow of plasma into the extracapillary space was considered. The effect of modulating several important parameters was investigated, namely, the Michaelis-Menten constant V(m) (the maximum oxygen consumption per unit volume of the cell mass), the oxygen partial pressure, the flow rate of the plasma at device inlet, and the permeability of the cell mass contained in the extracapillary space. A computer implementation of the model was used to assess whether a given number of cells could be maintained within such a device. The results suggest that a substantial proportion of the hepatocytes are exposed to hypoxic conditions under which metabolism may be impaired.
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