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Mechanism of Clinical Complication of Metal-on-Metal Total Hip Replacement: Nanoparticle Characterisation, Nanotoxicity, and Biological Metal Corrosion / Zhao Liu

DOI (Published version): 10.23889/Suthesis.51918

Abstract

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 a...

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Published: 2018
Institution: Swansea University
Degree level: Doctoral
Degree name: Ph.D
URI: https://cronfa.swan.ac.uk/Record/cronfa51918
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fullrecord <?xml version="1.0"?><rfc1807><datestamp>2019-09-17T11:22:00.2561592</datestamp><bib-version>v2</bib-version><id>51918</id><entry>2019-09-16</entry><title>Mechanism of Clinical Complication of Metal-on-Metal Total Hip Replacement: Nanoparticle Characterisation, Nanotoxicity, and Biological Metal Corrosion</title><swanseaauthors/><date>2019-09-16</date><abstract>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 &#x2018;ImageJ&#x2019; 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&#xF061; 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.</abstract><type>E-Thesis</type><journal/><publisher/><keywords>Metal-on-metal total hip arthroplasty (MoM THA), THP-1 macrophages, cytotoxicity, metal wear nanoparticles, metal corrosion</keywords><publishedDay>31</publishedDay><publishedMonth>12</publishedMonth><publishedYear>2018</publishedYear><publishedDate>2018-12-31</publishedDate><doi>10.23889/Suthesis.51918</doi><url/><notes>A selection of third party content is redacted or is partially redacted from this thesis.</notes><college>COLLEGE NANME</college><CollegeCode>COLLEGE CODE</CollegeCode><institution>Swansea University</institution><degreelevel>Doctoral</degreelevel><degreename>Ph.D</degreename><apcterm/><lastEdited>2019-09-17T11:22:00.2561592</lastEdited><Created>2019-09-16T16:20:49.3924941</Created><path><level id="1">Faculty of Medicine, Health and Life Sciences</level><level id="2">Swansea University Medical School - Medicine</level></path><authors><author><firstname>Zhao</firstname><surname>Liu</surname><order>1</order></author></authors><documents><document><filename>0051918-16092019163050.pdf</filename><originalFilename>Liu_Zhao_PhD_Thesis_Final_Embargoed30.08.2022_Redacted.pdf</originalFilename><uploaded>2019-09-16T16:30:50.7500000</uploaded><type>Output</type><contentLength>4182646</contentLength><contentType>application/pdf</contentType><version>Redacted version - open access</version><cronfaStatus>true</cronfaStatus><embargoDate>2022-08-30T00:00:00.0000000</embargoDate><copyrightCorrect>true</copyrightCorrect></document></documents><OutputDurs/></rfc1807>
spelling 2019-09-17T11:22:00.2561592 v2 51918 2019-09-16 Mechanism of Clinical Complication of Metal-on-Metal Total Hip Replacement: Nanoparticle Characterisation, Nanotoxicity, and Biological Metal Corrosion 2019-09-16 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. E-Thesis Metal-on-metal total hip arthroplasty (MoM THA), THP-1 macrophages, cytotoxicity, metal wear nanoparticles, metal corrosion 31 12 2018 2018-12-31 10.23889/Suthesis.51918 A selection of third party content is redacted or is partially redacted from this thesis. COLLEGE NANME COLLEGE CODE Swansea University Doctoral Ph.D 2019-09-17T11:22:00.2561592 2019-09-16T16:20:49.3924941 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Zhao Liu 1 0051918-16092019163050.pdf Liu_Zhao_PhD_Thesis_Final_Embargoed30.08.2022_Redacted.pdf 2019-09-16T16:30:50.7500000 Output 4182646 application/pdf Redacted version - open access true 2022-08-30T00:00:00.0000000 true
title Mechanism of Clinical Complication of Metal-on-Metal Total Hip Replacement: Nanoparticle Characterisation, Nanotoxicity, and Biological Metal Corrosion
spellingShingle Mechanism of Clinical Complication of Metal-on-Metal Total Hip Replacement: Nanoparticle Characterisation, Nanotoxicity, and Biological Metal Corrosion
,
title_short Mechanism of Clinical Complication of Metal-on-Metal Total Hip Replacement: Nanoparticle Characterisation, Nanotoxicity, and Biological Metal Corrosion
title_full Mechanism of Clinical Complication of Metal-on-Metal Total Hip Replacement: Nanoparticle Characterisation, Nanotoxicity, and Biological Metal Corrosion
title_fullStr Mechanism of Clinical Complication of Metal-on-Metal Total Hip Replacement: Nanoparticle Characterisation, Nanotoxicity, and Biological Metal Corrosion
title_full_unstemmed Mechanism of Clinical Complication of Metal-on-Metal Total Hip Replacement: Nanoparticle Characterisation, Nanotoxicity, and Biological Metal Corrosion
title_sort Mechanism of Clinical Complication of Metal-on-Metal Total Hip Replacement: Nanoparticle Characterisation, Nanotoxicity, and Biological Metal Corrosion
author ,
author2 Zhao Liu
format E-Thesis
publishDate 2018
institution Swansea University
doi_str_mv 10.23889/Suthesis.51918
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
active_str 0
description 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.
published_date 2018-12-31T04:03:58Z
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score 11.013731

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