Journal
ARTIFICIAL CELLS BLOOD SUBSTITUTES AND BIOTECHNOLOGY
Volume 35, Issue 6, Pages 585-606Publisher
INFORMA HEALTHCARE
DOI: 10.1080/10731190701586269
Keywords
bioreactor; hemoglobin; hemoglobin-based oxygen carrier; hepatocyte; hollow fiber bioreactor; mathematical model; oxygen carrier
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The production of a fully functional bioartificial liver assist device (BLAD) would greatly enhance available treatment options for patients suffering from acute liver failure. Currently, inadequate oxygen provision to hepatocytes seeded within hollow fiber bioreactors hampers development of a viable hollow fiber-based BLAD. Experimentally, oxygen provision to primary rat hepatocytes cultured within hollow fiber bioreactors was measured, it was observed that supplementation with an oxygen carrier (bovine red blood cells at similar to 2% human hematocrit) did not significantly improve oxygenation compared to the absence of an oxygen carrier. Therefore, an oxygen transport model of an individual hollow fiber within the bioreactor was developed and simulated (up to similar to 10% human hematocrit) to more fully examine the effect of oxygen carrier supplementation on oxygenation within the bioreactor. The modeling analysis, supported via the experimental results, was utilized to predict optimal bioreactor operating conditions for the delivery of in vivo-like oxygen gradients to cultured hepatocytes in clinically relevant settings.
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