The bioartificial liver assist device (BLAD) utilizes hepatocytes, maintained within an extracorporeal artificial device (commonly a hollow fiber (HF) bioreactor), to reproduce a broad range of liver functions. However, several challenges must still be overcome in the creation of a viable BLAD, including providing appropriate oxygenation to the hepatocytes. Maintaining hepatocyte viability and differentiated function is highly dependent on oxygen provision. 1 promising way to deliver and sustain adequate oxygen levels is through the addition of an oxygen carrier, such as bovine red blood cells (bRBCs), to the media circulating within the device. We hypothesize that the use of bRBCs within a BLAD will allow for increased oxygen delivery, thus promoting prolonged differentiated function and preservation of cell mass. We plan to test this hypothesis by pursuing the following 2 specific aims: 1) Measure and correlate the hepatic HF bioreactor global hepatocyte oxygen consumption (GHOC) with hepatocyte proliferation and metabolic and synthetic functions when bRBCs (either normal or cross-linked) are present in the circulating media at varied bRBC concentrations and at varied inlet partial pressures of oxygen;and 2) Measure and correlate the hepatic HF bioreactor GHOC with hepatocyte biotransformation and detoxification functions under differing oxygenation scenarios. This project is significant in that it is a detailed examination of the impact of oxygen levels on hepatocyte function and viability when cultured within a HF bioreactor;which to the best of our knowledge is not well understood. The success of any or both of these specific aims will aid in achieving the long-term goal of this application, which is to design a BLAD that is capable of sustaining a wide variety of liver functions. The knowledge gained from this study is expected to be of benefit in the design of hepatocyte containing HF bioreactors for use as potential BLADs.
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