Journal
PROCEEDINGS OF THE INSTITUTION OF MECHANICAL ENGINEERS PART H-JOURNAL OF ENGINEERING IN MEDICINE
Volume 215, Issue H5, Pages 479-486Publisher
PROFESSIONAL ENGINEERING PUBLISHING LTD
DOI: 10.1243/0954411011536073
Keywords
cyclic strain; wear particles; biologic response; cytokines; in vitro
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The effects of cyclic mechanical strain and challenge with physiologically relevant doses of submicrometre-size polyethylene (PE) particles on the osteolytic potential of primary human mononuclear phagocytes were investigated. Cells were seeded into a three-dimensional tissue matrix and co-cultured with particles (mean size 0.21 mum) at particle volume to cell number ratios of 7.5. 15, 30 and 100 mum(3)/cell. Matrices were then either cultured statically or subjected to 20 per cent cyclic compressional strain in the 'ComCell' for 16 h prior to the assessment of cell viability and quantification of the pro-inflammatory cytokine tumour necrosis factor alpha (TNF alpha). The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazdium bromide) assay was shown to be too insensitive to detect changes in cell viability. However, when quantified by the adenosine triphosphate (ATP) assay, cell viability was demonstrated to be reduced following exposure to cyclic strain. Macrophages cultured in the static three-dimensional tissue equivalent model produced very high levels of TNF alpha in response to submicrometre PE particles at a ratio of 100 mum(3)/cell. Cyclic strain in the absence of particles gave only a small increase in TNF alpha production. However. the combined effects of strain and particle stimulation at a ratio of 30 mum(3)/cell resulted in the secretion of significantly more TNF alpha than was produced by macrophages subjected to strain alone, or the cells-only control. This synergy between cyclic strain and PE particle stimulation was only evident when the volume of particles was reduced below the volume that maximally stimulated cells. These results suggest that while cyclic strain may not be the primary factor responsible for macrophage activation and periprosthetic osteolysis, at low particle load, it may contribute significantly to the osteolytic potential of macrophages in vitro or in vivo.
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