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Title: Mechanism of clinical complication of metal-on-metal total hip replacement : nanoparticle characterisation, nanotoxicity, and biological metal corrosion
Author: Liu, Zhao
ISNI:       0000 0004 7972 385X
Awarding Body: Swansea University
Current Institution: Swansea University
Date of Award: 2018
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Metal-on-Metal total hip arthroplasty (MoM THA) has undergone a recent resurgence as an important treatment for patients with end stage osteoarthritis. Despite the satisfactory short-term survivorship of the implant, revision surgeries caused by metal wear particles involved clinical complications are increasingly reported. Metal wear particles produced from failed implants have caused significant adverse local tissue reactions (ALTR) such as abnormal periprosthetic soft-tissue (pseudotumours). There are limited understandings of the potential mechanisms involved. The broad aim of this thesis was therefore to characterise metal wear nanoparticles recovered from tissue during revision, and to create in vitro modules to study the mechanism of nanotoxicity of the of metal wear nanoparticles and cell mediated corrosion. Metal wear products retrieved from three common types of hip replacements, including metal-on-metal resurfacing (MoM HRA), metal-on-metal large head total hip arthroplasty (MoM LHTHA) and non-metal-on-metal hip dual modular neck total hip arthroplasty (Non-MoM DMNTHA) were characterised. The shape, size and number of metal wear nanoparticles were quantified by Transmission electron microscopy (TEM) and 'ImageJ' analysis. The element composition of the retrieved tissue samples was detected through energy dispersive x-ray spectrometry (EDS). The results showed that the physical properties such as size, shape and number of metal wear nanoparticles were dependent on the type of hip replacement. The element composition of metal wear products retrieved were different due to different configuration of prostheses. Subsequent research focused on the cytotoxicity with Neutral Red assay and mechanism of different metallic nanoparticles interaction with THP-1 macrophages. The in vitro experiment demonstrated that metal nanoparticles induced cytotoxicity and cell death. Moreover, siRNA knock out study proved that HIF1 is likely to involve in cobalt nanoparticles (CoNPs) induced cellular cytotoxicity. The metal corrosion by macrophages was also studied by scanning electron microscopy (SEM) and white-light interferometry (WLI). In addition, macrophages involved extra cellular metal corrosion was detected with an in-house developed biosensor. The results showed that THP-1 macrophages were likely to corrode metal surface directly and produce electrochemical reaction at the cell-metal interface. In conclusion, clinical complication of MoM THA is closely related to metal wear nanoparticles; the clinically relevant metal nanoparticles are toxic to cells in vitro; metal corrosion by macrophages may release metal ions to contribute to the toxicity and ALTR.This study has created in vitro models to investigate the mechanism of clinical complication of MoM THA. Further work is required to reveal the molecular pathways and electrochemical reaction at the interface between cells and metal implants, which will benefit the improvement of total hip replacement technology.
Supervisor: Xia, Zhidao Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral