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Title: Development of a safety system and contaminant quantification methods for use within a bioartificial liver device
Author: Gibbons, Stephanie Annie
ISNI:       0000 0004 7228 5914
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2017
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The prognosis for patients with acute liver failure is poor, as such a novel method for the treatment of these patients is urgently required. The Liver Group bioartificial liver (BAL) has been developed to meet this need. The BAL consists of an extracorporeal circuit, in which the patient’s plasma is processed through an alginate-encapsulated HepG2 cellular biomass. These cells synthesise proteins and perform a detoxification function, replacing that of the patient’s own liver. The aim of this PhD thesis was to characterise a filtration system for incorporation within the BAL, enabling regulatory requirements for use in patients to be met. Specifically, the system was to remove potential contaminants originating from the biomass, such as cell debris and DNA. The filtration system was to also be assessed for the removal of endotoxin, originating from the patient as a cofactor of their liver failure, to aid the patient’s recovery. This thesis led to the development of a protocol for the incorporation of a filtration system into the BAL. Assays for the detection of DNA and endotoxin within human plasma samples were successfully optimised for use both in vitro and in vivo. These assays enabled the detection of DNA and endotoxin at a lower level concentration of 0.1 ng/μl and 1 EU/ml, respectively, facilitating characterisation of the safety system to sufficient sensitivity limits required to meet regulatory guidelines. DNA, endotoxin and particles were consistently removed from plasma samples by the filtration system, whilst beneficial components of the plasma such as albumin and fibrinogen, native to the patient or produced by the biomass, were maintained. To conclude, this thesis demonstrates that the filtration system was able to remove potential BAL-originating contaminants, meeting regulatory guidelines to enable its use in patients. The filtration system also demonstrated endotoxin removal capacity, providing an additional functional element of this system.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available