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Roles of corrosion products of metal hip replacements in the etiology of adverse local tissue reactions Eltit Guersetti, Felipe Yasser

Abstract

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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