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

H Lee,Joanne L Tipper,J B Phillips,R M Hall

doi:10.1007/s00586-019-06177-w

H Lee, Joanne L Tipper + Show 2 more

Open Access

https://doi.org/10.1007/s00586-019-06177-w

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Abstract

PurposeTotal 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.MethodsClinically 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.ResultsCoCr 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.ConclusionsThe 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 abstractThese slides can be retrieved under Electronic Supplementary Material.

Highlights

Significant economic and patient issues associated with early failure of metal-on-metal (MOM) total hip and resurfacing replacements have been the focus of the public and scientific1 3 Vol.:(0123456789)European Spine Journal (2020) 29:2701–2712 media recently [1]
The particles of cobalt chrome (CoCr) generated in this study were similar in terms of size and morphology to previous studies [20, When CoCr wear particles were cultured with primary rat astrocytes and microglial cells in 2D culture, cell viability was adversely affected by all doses of particles
When cells were exposed to stainless steel particles in 2D culture, initially an adverse effect was observed; this effect was only consistent at the highest particle concentration at the 5-day time point

Summary

Introduction

European Spine Journal (2020) 29:2701–2712 media recently [1] These events have led to concerns over other MOM implant systems, including those used in spinal surgery, where a number of articulating total disc replacements (TDRs) are still in use. TDRs comprise structures that have a large number of interfaces, e.g. endplate/bone interface, endplate screws and bone as well as the articulating surfaces All of these interacting surfaces may produce debris and/or ions with the potential to invoke adverse biological responses, which may lead to failure and device revision. There are reports that describe neurological symptoms, including radicular pain and paraparesis, in patients with metallosis associated with spinal devices [7, 13]. Inflammation would appear to be a key factor in the development of such symptoms; other reports describe late operative site pain [8, 9]

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