Consequences of exposure to peri-articular injections of micro- and nano-particulate cobalt-chromium alloy.
Metal hip replacements generate both metal particles and ions. The biological effects of peri-articular exposure to nanometre and micron sized cobalt chrome (CoCr) wear particles were investigated in a mouse model. Mice received injections of two clinically relevant doses of nanoparticles (32 nm), one of micron sized (2.9 μm) CoCr particles or vehicle alone into the right knee joint at 0, 6, 12 and 18 weeks. Mice were analysed for genotoxic and immunological effects 1, 4 and 40 weeks post exposure. Nanoparticles but not micron particles progressively corroded at the injection site. Micron sized particles were physically removed. No increase of Co or Cr was seen in peripheral blood between 1 and 40 weeks post exposure to particles. No significant inflammatory changes were observed in the knee tissues including ALVAL or necrosis. DNA damage was increased in bone marrow at one and forty weeks and in cells isolated from frontal cortex at 40 weeks after injection with nanoparticles. Mice exposed to the micron sized, but not nanoparticles became immunologically sensitized to Cr(III), Cr (VI) and Ni(II) over the 40 week period as determined by lymphocyte transformation and ELISpot (IFN-γ and IL-2) assays. The data indicated that the response to the micron sized particles was Th1 driven, indicative of type IV hypersensitivity. This study adds to understanding of the potential adverse biological reactions to metal wear products.
Institute of Medical & Biological Engineering, University of Leeds, Leeds, UK.
Christopher
C
Brown
Lizeth
L
Lacharme-Lora
Blessing
B
Mukonoweshuro
Aman
A
Sood
Roger B
RB
Newson
John
J
Fisher
C Patrick
CP
Case
Eileen
E
Ingham
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology*; D002857:Chromium / Q000378:metabolism; D002858:Chromium Alloys / Q000009:adverse effects*; D002869:Chromosome Aberrations / Q000187:drug effects; D003035:Cobalt / Q000378:metabolism; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects; D005260:Female; D007270:Injections, Intra-Articular; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D007719:Knee Joint / Q000187:drug effects / Q000473:pathology; D053768:Metal Nanoparticles / Q000009:adverse effects*; D051379:Mice; D008809:Mice, Inbred C3H; D010316:Particle Size; D017397:Prefrontal Cortex / Q000187:drug effects / Q000473:pathology*
D002858:Chromium Alloys; D007376:Interleukin-2; D002857:Chromium; D003035:Cobalt; D007371:Interferon-gamma
DNA damage; Hip replacement; Metal hypersensitivity; Metal-on-metal; Metallic particles