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Combination of cobalt, chromium and titanium nanoparticles increases cytotoxicity in vitro and pro-inflammatory cytokines in vivo

Zhao Liu Orcid Logo, Hui Liu, Rachel Vowden, Louise Hughes Orcid Logo, Dahu Qi, Wendy Francis Orcid Logo, Giorgio Perino, Ryan Pink Orcid Logo, Jun Xiao, Bin Li, Zhidao Xia Orcid Logo

Journal of Orthopaedic Translation, Volume: 38, Pages: 203 - 212

Swansea University Authors: Wendy Francis Orcid Logo, Zhidao Xia Orcid Logo

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    2022 The Authors. Published by Elsevier B.V. on behalf of Chinese Speaking Orthopaedic Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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DOI (Published version): 10.1016/j.jot.2022.10.013

Abstract

BackgroundThe mixture of different metallic nanoparticles released from intended and unintended wearing of orthopaedic implants such as the Co/Cr cup and head, Co/Cr sleeves or tapers and their interface with Ti stems in the case of hip prostheses are a leading cause of adverse inflammatory response...

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Published in: Journal of Orthopaedic Translation
ISSN: 2214-031X
Published: Elsevier BV 2023
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URI: https://cronfa.swan.ac.uk/Record/cronfa63234
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The in vivo effects were also evaluated after peri-tibial soft tissue injection in mice.ResultsThe results demonstrated that Co, Cr, and Ti nanoparticles and their combination were phagocytosed by macrophages both in vitro and in vivo. High doses of nanoparticles from each individual metal caused a variable rate of cell death in vitro. However, the mixture of Co/Cr/Ti nanoparticles was more toxic than the Co, Cr or Ti metals alone at low doses. Intracellular distribution of Co, Cr, and Ti in the combined group was heterogeneous and associated with distinct morphological features. The results from in vivo experiments showed a significant increase in the mRNA levels of interleukin (IL)-1β, IL-6, IL-8 and tumour necrosis factor (TNF)-α in peri-tibial soft tissue following the administration of Co alone as well as the combination of nanoparticles.ConclusionThis study demonstrated that the combination of Co/Cr/Ti nanoparticles was more cytotoxic than any of the individual metals in vitro and induced higher expression of genes encoding pro-inflammatory cytokines than single metals in vivo. The in vivo model utilised in this study might provide a useful tool for rapid assessment of the effects of unintended release of metal nanoparticles from implants in pre-/post-marketing studies.Translational potential of this articleThis study highlights the importance of preclinical assessments of potential nanoparticles produced by wear and tear of metal implants using macrophages and animal models, in particular their combinational toxicity in addition to the assessments of the bulk metallic materials.</abstract><type>Journal Article</type><journal>Journal of Orthopaedic Translation</journal><volume>38</volume><journalNumber/><paginationStart>203</paginationStart><paginationEnd>212</paginationEnd><publisher>Elsevier BV</publisher><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint>2214-031X</issnPrint><issnElectronic/><keywords>Metal nanoparticles, Macrophages, Cytotoxicity, Pro-inflammatory cytokines</keywords><publishedDay>1</publishedDay><publishedMonth>1</publishedMonth><publishedYear>2023</publishedYear><publishedDate>2023-01-01</publishedDate><doi>10.1016/j.jot.2022.10.013</doi><url>http://dx.doi.org/10.1016/j.jot.2022.10.013</url><notes/><college>COLLEGE NANME</college><department>Biomedical Sciences</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>BMS</DepartmentCode><institution>Swansea University</institution><apcterm>SU Library paid the OA fee (TA Institutional Deal)</apcterm><funders>We would like to acknowledge the Thackray Medical Research Trust for financial support of a MSc studentship of this project and Christopher von Ruhland, PhD for samples preparation for TEM/SEM analysis.</funders><projectreference/><lastEdited>2024-02-02T08:37:11.0482303</lastEdited><Created>2023-04-24T17:39:52.7452121</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><orcid>0000-0002-2709-9018</orcid><order>1</order></author><author><firstname>Hui</firstname><surname>Liu</surname><order>2</order></author><author><firstname>Rachel</firstname><surname>Vowden</surname><order>3</order></author><author><firstname>Louise</firstname><surname>Hughes</surname><orcid>0000-0002-7505-202x</orcid><order>4</order></author><author><firstname>Dahu</firstname><surname>Qi</surname><order>5</order></author><author><firstname>Wendy</firstname><surname>Francis</surname><orcid>0000-0002-7952-2770</orcid><order>6</order></author><author><firstname>Giorgio</firstname><surname>Perino</surname><order>7</order></author><author><firstname>Ryan</firstname><surname>Pink</surname><orcid>0000-0001-7501-558x</orcid><order>8</order></author><author><firstname>Jun</firstname><surname>Xiao</surname><order>9</order></author><author><firstname>Bin</firstname><surname>Li</surname><order>10</order></author><author><firstname>Zhidao</firstname><surname>Xia</surname><orcid>0000-0002-2047-7282</orcid><order>11</order></author></authors><documents><document><filename>63234__27594__20cac7ce2d43435da6e1786faacaa38a.pdf</filename><originalFilename>63234.pdf</originalFilename><uploaded>2023-05-24T12:45:04.2648040</uploaded><type>Output</type><contentLength>3051530</contentLength><contentType>application/pdf</contentType><version>Version of Record</version><cronfaStatus>true</cronfaStatus><documentNotes>2022 The Authors. 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spelling v2 63234 2023-04-24 Combination of cobalt, chromium and titanium nanoparticles increases cytotoxicity in vitro and pro-inflammatory cytokines in vivo f0ec2a3fdae1cf112579d579afbe9813 0000-0002-7952-2770 Wendy Francis Wendy Francis true false c9307abfed1b43987a19da0c0e30d7a4 0000-0002-2047-7282 Zhidao Xia Zhidao Xia true false 2023-04-24 BMS BackgroundThe mixture of different metallic nanoparticles released from intended and unintended wearing of orthopaedic implants such as the Co/Cr cup and head, Co/Cr sleeves or tapers and their interface with Ti stems in the case of hip prostheses are a leading cause of adverse inflammatory responses and cytotoxicity to the host.MethodsThis study assessed the in vitro cytotoxic effects of three metallic nanoparticles (Co, Cr and Ti) separately and in combination on macrophages. The in vivo effects were also evaluated after peri-tibial soft tissue injection in mice.ResultsThe results demonstrated that Co, Cr, and Ti nanoparticles and their combination were phagocytosed by macrophages both in vitro and in vivo. High doses of nanoparticles from each individual metal caused a variable rate of cell death in vitro. However, the mixture of Co/Cr/Ti nanoparticles was more toxic than the Co, Cr or Ti metals alone at low doses. Intracellular distribution of Co, Cr, and Ti in the combined group was heterogeneous and associated with distinct morphological features. The results from in vivo experiments showed a significant increase in the mRNA levels of interleukin (IL)-1β, IL-6, IL-8 and tumour necrosis factor (TNF)-α in peri-tibial soft tissue following the administration of Co alone as well as the combination of nanoparticles.ConclusionThis study demonstrated that the combination of Co/Cr/Ti nanoparticles was more cytotoxic than any of the individual metals in vitro and induced higher expression of genes encoding pro-inflammatory cytokines than single metals in vivo. The in vivo model utilised in this study might provide a useful tool for rapid assessment of the effects of unintended release of metal nanoparticles from implants in pre-/post-marketing studies.Translational potential of this articleThis study highlights the importance of preclinical assessments of potential nanoparticles produced by wear and tear of metal implants using macrophages and animal models, in particular their combinational toxicity in addition to the assessments of the bulk metallic materials. Journal Article Journal of Orthopaedic Translation 38 203 212 Elsevier BV 2214-031X Metal nanoparticles, Macrophages, Cytotoxicity, Pro-inflammatory cytokines 1 1 2023 2023-01-01 10.1016/j.jot.2022.10.013 http://dx.doi.org/10.1016/j.jot.2022.10.013 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University SU Library paid the OA fee (TA Institutional Deal) We would like to acknowledge the Thackray Medical Research Trust for financial support of a MSc studentship of this project and Christopher von Ruhland, PhD for samples preparation for TEM/SEM analysis. 2024-02-02T08:37:11.0482303 2023-04-24T17:39:52.7452121 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Zhao Liu 0000-0002-2709-9018 1 Hui Liu 2 Rachel Vowden 3 Louise Hughes 0000-0002-7505-202x 4 Dahu Qi 5 Wendy Francis 0000-0002-7952-2770 6 Giorgio Perino 7 Ryan Pink 0000-0001-7501-558x 8 Jun Xiao 9 Bin Li 10 Zhidao Xia 0000-0002-2047-7282 11 63234__27594__20cac7ce2d43435da6e1786faacaa38a.pdf 63234.pdf 2023-05-24T12:45:04.2648040 Output 3051530 application/pdf Version of Record true 2022 The Authors. Published by Elsevier B.V. on behalf of Chinese Speaking Orthopaedic Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). true eng http://creativecommons.org/licenses/by-nc-nd/4.0/
title Combination of cobalt, chromium and titanium nanoparticles increases cytotoxicity in vitro and pro-inflammatory cytokines in vivo
spellingShingle Combination of cobalt, chromium and titanium nanoparticles increases cytotoxicity in vitro and pro-inflammatory cytokines in vivo
Wendy Francis
Zhidao Xia
title_short Combination of cobalt, chromium and titanium nanoparticles increases cytotoxicity in vitro and pro-inflammatory cytokines in vivo
title_full Combination of cobalt, chromium and titanium nanoparticles increases cytotoxicity in vitro and pro-inflammatory cytokines in vivo
title_fullStr Combination of cobalt, chromium and titanium nanoparticles increases cytotoxicity in vitro and pro-inflammatory cytokines in vivo
title_full_unstemmed Combination of cobalt, chromium and titanium nanoparticles increases cytotoxicity in vitro and pro-inflammatory cytokines in vivo
title_sort Combination of cobalt, chromium and titanium nanoparticles increases cytotoxicity in vitro and pro-inflammatory cytokines in vivo
author_id_str_mv f0ec2a3fdae1cf112579d579afbe9813
c9307abfed1b43987a19da0c0e30d7a4
author_id_fullname_str_mv f0ec2a3fdae1cf112579d579afbe9813_***_Wendy Francis
c9307abfed1b43987a19da0c0e30d7a4_***_Zhidao Xia
author Wendy Francis
Zhidao Xia
author2 Zhao Liu
Hui Liu
Rachel Vowden
Louise Hughes
Dahu Qi
Wendy Francis
Giorgio Perino
Ryan Pink
Jun Xiao
Bin Li
Zhidao Xia
format Journal article
container_title Journal of Orthopaedic Translation
container_volume 38
container_start_page 203
publishDate 2023
institution Swansea University
issn 2214-031X
doi_str_mv 10.1016/j.jot.2022.10.013
publisher Elsevier BV
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
url http://dx.doi.org/10.1016/j.jot.2022.10.013
document_store_str 1
active_str 0
description BackgroundThe mixture of different metallic nanoparticles released from intended and unintended wearing of orthopaedic implants such as the Co/Cr cup and head, Co/Cr sleeves or tapers and their interface with Ti stems in the case of hip prostheses are a leading cause of adverse inflammatory responses and cytotoxicity to the host.MethodsThis study assessed the in vitro cytotoxic effects of three metallic nanoparticles (Co, Cr and Ti) separately and in combination on macrophages. The in vivo effects were also evaluated after peri-tibial soft tissue injection in mice.ResultsThe results demonstrated that Co, Cr, and Ti nanoparticles and their combination were phagocytosed by macrophages both in vitro and in vivo. High doses of nanoparticles from each individual metal caused a variable rate of cell death in vitro. However, the mixture of Co/Cr/Ti nanoparticles was more toxic than the Co, Cr or Ti metals alone at low doses. Intracellular distribution of Co, Cr, and Ti in the combined group was heterogeneous and associated with distinct morphological features. The results from in vivo experiments showed a significant increase in the mRNA levels of interleukin (IL)-1β, IL-6, IL-8 and tumour necrosis factor (TNF)-α in peri-tibial soft tissue following the administration of Co alone as well as the combination of nanoparticles.ConclusionThis study demonstrated that the combination of Co/Cr/Ti nanoparticles was more cytotoxic than any of the individual metals in vitro and induced higher expression of genes encoding pro-inflammatory cytokines than single metals in vivo. The in vivo model utilised in this study might provide a useful tool for rapid assessment of the effects of unintended release of metal nanoparticles from implants in pre-/post-marketing studies.Translational potential of this articleThis study highlights the importance of preclinical assessments of potential nanoparticles produced by wear and tear of metal implants using macrophages and animal models, in particular their combinational toxicity in addition to the assessments of the bulk metallic materials.
published_date 2023-01-01T08:37:10Z
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