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Queen Mary University of LondonQueen Mary University of London
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School of Engineering and Materials Science
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PhD Thesis: The inflammatory response to particulate wear debris in the context of total hip replacements

Author: ALTAF, H

Year: 2007

Supervisor(s): Julia Shelton

It was postulated that the inflammatory response to wear debris deposition involves both T cells and antigen presenting cells (APC) and therefore may be immunologically-mediated. This study established the presence of APC and T cells in situ and by use of immunohistochemical techniques, the novel and preliminary identification of the expression transcription factors (NFkB and NF-IL6) in situ in the same bone-implant interface tissues was also established.

An assessment of the inflammatory potential of biomaterial particles was performed based on the size of particles. A comparison of two diamond nanoparticulate aggregates; one within the critical size range for macrophage activation and one outside this, was performed to provide novel information regarding the cellular response to aggregates of nanoparticles. The results from these experiments showed the larger microparticles to incite a greater up-regulation of NFkB, cytokines and costimulatory molecules in two cell models in comparison to the smaller nanoparticle aggregates.

The third aim of this thesis was to examine the effectiveness of two inhibitors of NFkB activation by examination of the expression of costimulatory molecule, cytokine and NFkB factors in cells stimulated with biomaterial particles in the presence of these inhibitors. NFkB inhibitors successfully down-regulated the cellular response to particles, with a decreased expression of NFkB factors, cytokines and costimulatory molecules. In addition, these in vitro investigations provided evidence of the particles utilising distinct NFkB activation pathways depending on their size. In combination these findings shed light upon the complexities of the inflammatory response associated with THR failure and identify NFkB as a prime target for therapeutic intervention.