Bas Masri

About two million people receive hip implants annually, to relieve the pain generated by osteoarthritis. Hip implants are composed of a titanium femoral stem and a Co-Cr-Mo head that articulates with a titanium-alloy acetabular cup, covered by a polyethylene liner (MoP). Other designs directly use a metal (Co-Cr-Mo) acetabular articulating surface (MoM). Concerns have arisen due to the elevated numbers of adverse local tissue reactions (ALTRs) to hip implants that generate pain and soft-tissue destruction. Due to the high rates of ALTRs in MoM implants, the corrosion products or wear particles from the metal surfaces are thought to trigger the immunological reactions. This thesis aimed to understand the mechanisms of ALTRs development through three studies: 1) histological analyses and comparison of ALTRs in MoM and MoP implants. 2) analysis of corrosion products in synovial fluid and tissues. 3) mechanistic study based on gene expression analysis of ALTRs, and cell culture of primary synovial fibroblasts that were exposed to Cr and Co.
 The histological description of ALTRs showed structural similarities between MoM and MoP, with common elements such as tissue necrosis and the presence of perivascular lymphocyte aggregates. Significantly higher levels of metal ions were found in the synovial fluid of ALTR patients, but no differences in the particles present in tissues were found in ALTRs compared to non-ALTRs. The gene expression analysis of lymphocytes aggregates found an identical and non-specific Th1/Th2 reaction in ALTRs in both MoM and MoP, with no evidence of Th17 reaction. Finally, primary synovial fibroblasts responded to concentrations of metal ions observed in the synovial fluid of patients, by releasing pro-inflammatory cytokines. After 24 hours of exposure the secreted cytokines were demonstrated to be chemotactic for human monocytes which is a key processes during inflammation.These results support the hypothesis that metal ions from the hip implants trigger cytokine secretion by synovial fibroblasts, which initiate the immune reaction to hip replacements, providing evidence to reject the hypothesis of hypersensitivity as an etiologic factor of ALTRs.

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Revision total hip arthroplasty with femoral impaction allografting has an attractive potential for restoring bone stock in femurs with bone loss caused by the failure of hip implants. However, problematic implant subsidence is often reported after this procedure. A lack of understanding remains over the mechanisms that cause subsidence. The objectives of this study were to: a) explore the relationships between subsidence and morphometric features of the graft and bone cement regions after femoral impaction allografting in a cadaveric femur model; b) characterize mechanical properties of the graft bed as a function of impaction force, and explore new alternative graft compaction methods; and c) develop a finite element model to investigate the key mechanisms that contribute to initial implant subsidence. High levels of cement penetration into the graft bed were observed, resulting in extensive regions of cement contact with the host bone in a cadaveric femur model. The implant subsidence correlated negatively with the amount of cement-endosteum contact. The density, compression stiffness and shear strength of the graft were proportional to the impaction force. A slower alternative graft compaction method resulted in higher graft stiffness and shear strength than traditional graft impaction, but the benefit of this new compaction method was small compared to the effect of increasing the impaction force. In a finite element model, the relationship between graft density and subsidence was dependant on cement penetration profile. Without cement-endosteum contact, subsidence decreased with increasing graft density; however, graft density did not affect subsidence in constructs with cement-endosteum contact. Initial subsidence was primarily attributed to slippage at the stem-cement and endosteum interfaces, and the latter mechanism was greatly affected by changes in graft density and cement penetration profile. This study demonstrated that extensive cement penetration can occur in femoral impaction allografting, which may compromise the potential for new bone formation but may be important in preventing excessive subsidence. The endosteum interface was identified as a key factor in the development of subsidence. Finally, our results indicate that the potential benefit of achieving a denser graft bed depends upon the cement penetration profile.

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