Gibbons, Stephanie Annie;
(2017)
Development of a safety system and contaminant quantification methods for use within a bioartificial liver device.
Doctoral thesis (Ph.D), UCL (University College London).
Preview |
Text
Gibbons_10040316_thesis.pdf Download (3MB) | Preview |
Abstract
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.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Development of a safety system and contaminant quantification methods for use within a bioartificial liver device |
| Event: | UCL (University College London) |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| UCL classification: | UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10040316 |
Archive Staff Only
 |
View Item |
