Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.598034
Title: Determination of the biological response and cellular uptake mechanisms of nanometre-sized UHMWPE wear particles from total hip replacements
Author: Liu, Aiqin
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2012
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Abstract:
The biological response to ultra-high molecular weight polyethylene (UHMWPE) wear particles has been shown to play a key role in the development of osteolysis, which leads to aseptic loosening of total hip replacements (THR). Recently, nanometre-sized UHMWPE particles have been identified in vivo and in vitro from hip and knee replacements. It has been shown that nanometre-sized Ceridust, which are model polymer particles. can stimulate human macrophages to produce significant levels of osteolytic cytokines. Therefore, the aims of this study were to investigate the cellular response to and cellular uptake mechanisms of clinically-relevant nanometre-sized UHMWPE wear particles. A large volume of aseptic clinically-relevant nanometre-sized UHMWPE wear particles with a mode size of 30•40 nm was isolated from RPMI 1640 medium lubricants from pin-on- plate wear testing. Nanometre-sized UHMWPE wear particles with a mode size of 30-40 nm and nanometre-sized Ceridust with a mode size of 20•30 nm had no significant effect on osteolytic cytokine re lease, including TNF•α, IL•Iβ, IL•6 and lL-8, from human peripheral blood mononuclear cells (PBMNC's) isolated from all donors (3 donors) tested at a concentration of 100 J..lm3 particles per cell after 12 hours and 24 hours. The micrometre-size UHMWPE wear particles with a mode size of 0.1 - 1.0 μm and 40 nm polystyrene particles (FluoSpheres) with a mode size of 50•60 nm caused significantly elevated osteolytic cytokine release from all of the donors tested at a concentration of 100 μm3 particles per cell after 12 hours and 24 hours. The results indicated that there is a lower size limit « 50 nm) for cellular activation. Clathrin-mediated endocytosis and caveolae-mediated endocytosis were both involved in the internalisation of nanometre-sized UHMWPE wear particles with a size mode of 30•40 nm and micrometre-sized UHMWPE wear particles with a size mode of 0.1•1.0 μm within PBMNC's. Clathrin-mediated endocytosis but not the caveolae-mediated pathway was involved in the internalisation of the 40 nm FluoSpheres within PBMNC's. The results showed clear evidence that there was a relationship between the mechanism of particle uptake and the cellular response to particles with different compositions.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.598034  DOI: Not available
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