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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Abstract: 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. Methods: 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. Results: 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. Conclusions: 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.[Figure not available: see fulltext.]

Original languageEnglish
Pages (from-to)2701-2712
Number of pages12
JournalEuropean Spine Journal
Volume29
Issue number11
DOIs
Publication statusPublished - Nov 2020

Bibliographical note

Funding Information:
The research was funded by the Engineering and Physical Sciences Research Council, UK, through a Ph.D. scholarship to HL through the Centre for Doctoral Training Medical and Biological Engineering, School of Mechanical Engineering, University of Leeds, UK.

Publisher Copyright:
© 2019, The Author(s).

Keywords

  • Cobalt chromium
  • Glial cells
  • Metal wear particles
  • Stainless steel
  • Total disc replacements (TDR)

ASJC Scopus subject areas

  • Surgery
  • Orthopedics and Sports Medicine

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