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Title: Characterisation and biological impact of wear particles from composite ceramic hip replacements
Author: Asif, Imran Mohammed
ISNI:       0000 0004 7225 6750
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2018
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The high prevalence of osteolysis and aseptic loosening associated with the wear particles of conventional metal-on-UHMWPE (MoP) total hip replacements (THRs), and concerns over the release of metal wear particles and metal ions around the body from metal-on-metal (MoM) THRs, led to the development of alternative ceramic-on-ceramic (CoC) THRs. CoC bearings are of great interest due to their superior wear properties, compared to MoP and MoM bearings. Historically, ceramic THRs had a reputation for fracture, and recent issues have centred around surgical positioning and squeaking. The development of improved manufacturing methods allowed major improvements of ceramics which led to the introduction of composite ceramics for example, zirconia-toughened, platelet reinforced alumina or ZTA, otherwise commercially known as BIOLOX® Delta. The wear performance of composite CoC THRs such as those using BIOLOX® Delta has been extensively investigated, however no studies have reported the combined characteristics and biocompatibility of the wear debris generated from these bearings. Understanding wear particle characteristics and their biological activity is an essential step in the pre-clinical testing of joint replacements. However, currently for composite ZTA CoC bearings there is a lack of relevant studies, due to difficulties in generating high volumes of clinically-relevant ceramic wear debris in vitro, in addition current particle isolation methods are not sensitive enough to reliably isolate wear particles from hip simulator lubricants, due to the inherent low wear rates of the composite ZTA ceramics. Hence, the particles have not been systematically characterised and therefore little is known about their size, morphology and biological responses. Therefore, the aim of this study was to investigate the characteristics and biological activity of wear particles generated from composite BIOLOX® Delta ZTA CoC THRs. This study developed a two-step particle isolation method and subsequently applied it to hip simulator lubricants for the isolation of composite ceramic wear particles generated from BIOLOX® Delta CoC bearings tested under edge loading conditions. The high sensitivity of this new particle isolation method coupled with its effective removal of protein, allowed the successful recovery and characterisation of very low volumes of both micro and nano-scale wear particles, generated from composite ZTA CoC hip replacements for the first time. The recovered wear particles demonstrated a bimodal size range, which has been previously reported for wear particles generated from alumina ceramic hip replacements. A comprehensive evaluation of the biological impact of commercially-obtained composite BIOLOX® Delta ZTA ceramic model particles and clinically-relevant composite BIOLOX® Delta ZTA ceramic wear particles was investigated in terms of cytotoxicity, inflammation, genotoxicity and oxidative stress. The clinically-relevant composite ZTA ceramic wear particles were generated in water lubricant using a hip simulator under severe edge loading conditions. The biological impact of the ceramic particles was assessed using L929 fibroblast cells and peripheral blood mononuclear cells (PBMNCs) isolated from healthy human donors. Both the model and clinically-relevant BIOLOX® Delta ceramic wear particles demonstrated significant reduction in the viability of L929 fibroblast cells at very high doses (500μm3 of particles per cell), however no cytotoxic effects were observed at the lower clinically-relevant doses (0.5-0.05μm3 per cell). The BIOLOX® Delta ZTA ceramic model particles failed to stimulate an inflammatory response in terms of TNF-α release and did not cause any significant DNA damage or production of reactive oxygen species (oxidative stress) in PBMNCs from all donors. However, high doses (50μm3 per cell) of clinically-relevant BIOLOX® Delta ZTA ceramic wear particles caused significantly elevated levels of TNF-α release from PBMNCs. But, there were no significant effects in terms of DNA damage and oxidative stress in PBMNCs from all donors. This study demonstrated that there was a threshold volume of clinically-relevant ceramic wear particles required to stimulate significant TNF-α release from PBMNCs. However, these doses were not clinically-relevant and highly unlikely to occur in vivo due to the extremely low wear rates of CoC bearings. This comprehensive study indicated that composite ZTA Delta ceramic hip replacements had a low biological impact, which may enhance long-term clinical performance. The results from this study are only relevant for BIOLOX® Delta ZTA ceramics and not other manufacturers ceramics.
Supervisor: Tipper, Joanne ; Williams, Sophie ; Al-Hajjar, Mazen ; Fisher, John ; Anderson, James Sponsor: EPSRC ; Depuy Synthes
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available