Enhanced oxygen delivery to primary hepatocytes within a hollow fiber bioreactor facilitated via hemoglobin-based oxygen carriers.
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 approximately 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 approximately 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.
Sullivan
Jesse P
JP
Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, IN, USA.
Gordon
Jason E
JE
Bou-Akl
Therese
T
Matthew
Howard W T
HW
Palmer
Andre F
AF
D000818:Animals; D019149:Bioreactors; D018929:Cell Culture Techniques / Q000295:instrumentation; D019069:Cell Respiration; D002478:Cells, Cultured; D003198:Computer Simulation; D016503:Drug Delivery Systems / Q000379:methods*; D004867:Equipment Design; D006454:Hemoglobins / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D019164:Liver, Artificial; D008954:Models, Biological; D010100:Oxygen / Q000008:administration & dosage* / Q000378:metabolism; D051381:Rats
D006454:Hemoglobins; D010100:Oxygen