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29.10.2019 | Original Article Open Access

Neural cell responses to wear debris from metal-on-metal total disc replacements

European Spine Journal
H. Lee, J. B. Phillips, R. M. Hall, Joanne L. Tipper
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s00586-019-06177-w) contains supplementary material, which is available to authorized users.

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Total disc replacements, comprising all-metal articulations, are compromised by wear and particle production. Metallic wear debris and ions trigger a range of biological responses including inflammation, genotoxicity, cytotoxicity, hypersensitivity and pseudotumour formation, therefore we hypothesise that, due to proximity to the spinal cord, glial cells may be adversely affected.


Clinically relevant cobalt chrome (CoCr) and stainless steel (SS) wear particles were generated using a six-station pin-on-plate wear simulator. The effects of metallic particles (0.5–50 μm3 debris per cell) and metal ions on glial cell viability, cellular activity (glial fibrillary acidic protein (GFAP) expression) and DNA integrity were investigated in 2D and 3D culture using live/dead, immunocytochemistry and a comet assay, respectively.


CoCr wear particles and ions caused significant reductions in glial cell viability in both 2D and 3D culture systems. Stainless steel particles did not affect glial cell viability or astrocyte activation. In contrast, ions released from SS caused significant reductions in glial cell viability, an effect that was especially noticeable when astrocytes were cultured in isolation without microglia. DNA damage was observed in both cell types and with both biomaterials tested. CoCr wear particles had a dose-dependent effect on astrocyte activation, measured through expression of GFAP.


The results from this study suggest that microglia influence the effects that metal particles have on astrocytes, that SS ions and particles play a role in the adverse effects observed and that SS is a less toxic biomaterial than CoCr alloy for use in spinal devices.

Graphic abstract

These slides can be retrieved under Electronic Supplementary Material.

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Online Resources 1. High-resolution scanning electron micrograph and corresponding trace produced by energy-dispersive X-ray analysis (EDX) of cobalt chromium particles (PPTX 717 kb)
Supplementary material 2 (PPTX 716 kb)
Online Resources 2. High-resolution scanning electron micrograph and corresponding trace produced by energy-dispersive X-ray analysis (EDX) of stainless steel particles (PPTX 64 kb)
Supplementary material 4 (PPTX 58 kb)
Supplementary material 5 (PPTX 9687 kb)
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