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Title: Toxicity of metal debris from hip implants
Author: Swiatkowska, Ilona
ISNI:       0000 0004 8507 7807
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2019
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Hip implants are commonly made of cobalt-chromium and titanium alloys. Once inside the body, implants wear and corrode, releasing metal particles and ions into the local tissue and blood. Metal debris can cause local adverse effects, such as bone loss and tissue necrosis, ultimately leading to implant failure. More recently, systemic cobalt toxicity has gained publicity as reports of neurotoxicity, cardiomyopathy and hypothyroidism increased among recipients of metal hip implants. Widespread dissemination of metal debris, and its accumulation in organ tissue, is of a particular concern. The aim of this thesis is to better understand how metallic implant debris affects the body, and how blood metal levels relate to any toxicity symptoms. Prevalence of neurotoxicity and cognitive decline among patients with a history of highly elevated blood cobalt was assessed, using a set of validated questionnaires. Although a number of statistically significant differences were detected between the high cobalt group and controls, clinically relevant neuro-cognitive adverse effects were not observed. Distribution and chemical speciation of cobalt, chromium and titanium deposits were investigated in cadaveric samples of organs from hip replacement patients. Though synchrotron analysis identified the presence of highly oxidised chromium, further work is needed to assess if the results can be extrapolated to the in vivo situation. Genetic factors that might predispose some patients to the adverse effects of cobalt were explored in vitro, using CRISPR/Cas9 gene editing technology. Results of the feasibility study identified several candidate genes for further investigation. Blood titanium was measured in a large group of patients with titanium-based implants, using high resolution ICP-MS. This allowed a reliable laboratory reference range to be defined for use in future patient monitoring. Results from this thesis inform on potential consequences of implant degradation, and demonstrate the clinical utility of blood metal measurements to monitor implant performance.
Supervisor: Hart, A. ; Floto, A. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available