title: Effects of clinically relevant alumina ceramic wear particles on TNF-alpha production by human peripheral blood mononuclear phagocytes.
abstract: The recent introduction of microseparation of the components of ceramic-on-ceramic hip prostheses during hip simulations has produced clinically relevant wear rates, wear patterns and wear particles. This provided an opportunity to determine the response of primary human peripheral blood mononuclear cells to clinically relevant alumina ceramic wear particles in vitro. Alumina ceramic wear particles were generated in a hip joint simulator under microseparation conditions. The particles showed a bi-modal size distribution with nanometer sized (5-20nm) and larger particles (0.2->10 micrometer). The particles were cultured with human peripheral blood mononuclear cells obtained from six different donors at particle volume to cell number ratios of 1, 10, 100 and 500 micrometer(3). After 24h incubation the viability of the cells and the levels of TNF-alpha were determined. The response to the microseparation wear particles was compared to that of commercially available alumina powder with a uniform morphology and mean size of 0.5 micrometer. All six Donors PBMNC produced significantly elevated levels of TNF-alpha when stimulated with 100 micrometer(3) of the alumina powder per cell. Volumetric concentrations of 10 and 1.0 micrometer(3) per cell failed to stimulate a significant response by the cells from any of the six donors. Three of the six Donors PBMNC secreted significantly elevated levels of TNF-alpha when stimulated with 100 micrometer(3) of the microseparation wear particles, whereas the other three failed to respond to the wear debris at this concentration. All of the Donors PBMNC produced significantly elevated levels of TNF-alpha when stimulated with 500 micrometer(3) of the microseparation wear particles per cell. Thus, a greater volume of the microseparation wear particles was required to activate the PBMNC than the alumina powder. This was probably due to the microseparation wear particles having fewer particles in the critical size range (0.1-1 micrometer) for macrophage activation compared to the alumina powder. It can be concluded that alumina ceramic wear particles generated under microseparation conditions are capable of inducing osteolytic cytokine production by human mononuclear phagocytes. However, the volumetric concentration of the particles needed to generate this response is extremely high and given the low wear rates (<4mm(3) per million cycles) of ceramic-on-ceramic bearings, even under severe microseparation conditions, it is unlikely that this concentration threshold will be achieved in vivo.
authors.affiliation: Division of Microbiology, Department of Biochemistry and Molecular Biology, Institute of Medical and Biological Engineering, University of Leeds, LS2 9JT, Leeds, UK.
authors.forename: A
authors.initials: A
authors.lastname: Hatton
authors.forename: J E
authors.initials: JE
authors.lastname: Nevelos
authors.forename: J B
authors.initials: JB
authors.lastname: Matthews
authors.forename: J
authors.initials: J
authors.lastname: Fisher
authors.forename: E
authors.initials: E
authors.lastname: Ingham
mesh_terms: D000535:Aluminum / Q000494:pharmacology*; D001672:Biocompatible Materials / Q000494:pharmacology / Q000633:toxicity*; D018929:Cell Culture Techniques; D002470:Cell Survival; D002516:Ceramics / Q000494:pharmacology*; D006622:Hip Prosthesis / Q000009:adverse effects; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D011475:Prosthesis Failure; D013314:Stress, Mechanical; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D001672:Biocompatible Materials; D014409:Tumor Necrosis Factor-alpha; D000535:Aluminum