Thesis

A hybrid artificial liver with integral membrane oxygenation : theory, developmental studies and prototype testing

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Awarding institution
  • University of Strathclyde
Date of award
  • 1997
Thesis identifier
  • T9496
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Abstract
  • The purpose of this thesis is to identify, develop and evaluate a bioreactor design appropriate for use in a liver support system. The requirement for such systems is placed in context by discussing liver failure and options for therapy. The thesis objective is pursued by examining the natural organ and considering how the microarchitecture of the liver facilitates organ function. Thereafter, current bioartificial liver designs are studied with emphasis on analysis of; cell source, predicted mass transfer performance and mode of application. Reported clinical findings are also assessed. The experimental work investigates the influence of cell species, medium formulation and culture configuration on key liver function parameters. The oxygen consumption rate of hepatocytes under load and their response to fluid shear stress is investigated in order to develop design rules for the prototype bioreactor. The concluding work describes the development and testing of the bioreactor. The microarchitecture of the liver proves to be adapted for efficient mass exchange and characterised by large capacity upstream processes and downstream fine tuning of solute concentrations facilitating organ function. The current designs analyzed are shown to have shortcomings especially with respect to oxygen transfer. These shortcomings seem more serious when the oxygen consumption experimental results are considered. The oxygen consumption rate recorded exceeds previously reported values and is significant since the experimental conditions are more akin to those anticipated in clinical application. These findings make a compelling argument for integral oxygenation in hepatocyte bioreactors. The hepatocytes responded favourably to shear stresses suggesting that from mechanical and functional perspectives, designs based on direct contact between hepatocytes and plasma are feasible. This configuration offers mass transfer advantages. The resultant prototype bioreactor offers efficient mass transfer and control of cell surface pO2. In vitro testing demonstrates maintenance of urea synthetic activity for nine days under continuous ammonium load.
Advisor / supervisor
  • Courtney, James M.
  • Gaylor, John D.S.
  • Grant, Helen
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DOI

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