Oxygen Transport within a Hepatic Hollow Fiber Bioreactor

Hepatic hollow fiber bioreactors are considered a promising class of bioartificial liver assist device (BLAD). Unfortunately, the development of this type of device is currently hindered by oxygen limited transport to cultured hepatocytes, due to the low solubility of oxygen in aqueous media. A priori knowledge of the dissolved oxygen concentration (pO2) profile within a hepatic hollow fiber bioreactor is important in designing an effective BLAD. In designing BLADs for clinical use, it is important to note that hepatocytes in vivo experience a spectrum of oxygen tensions (pO2 ranging from 25 – 70 mmHg). This pO2 gradient in the liver sinusoid is extremely important for the development of proper differentiated function (zonation) of hepatocyte phenotypes. In order to provide an in vivo-like oxygen spectrum to cultured hepatocytes housed within a hollow fiber bioreactor, several different engineering approaches were explored. These included: supplementing the circulating media stream of the hollow fiber bioreactor with a hemoglobin-based oxygen carrier (HBOC) with defined oxygen binding and release kinetics; inoculating different types of hepatocytes; operating the bioreactor with the extracapillary space (ECS) ports open and closed; and varying several other operating parameters of the bioreactor system. We hypothesize that these parameters can be manipulated to improve hepatocyte oxygenation and attain the desired in vivo pO2 spectrum. Provision of proper oxygen conditions should create a fully functional BLAD that could potentially help thousands of liver failure patients.