Neural cell responses to wear debris from metal-on-metal total disc replacements
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ORIGINAL ARTICLE
Neural cell responses to wear debris from metal‑on‑metal total disc replacements H. Lee1 · J. B. Phillips2 · R. M. Hall1 · Joanne L. Tipper1,3 Received: 30 April 2019 / Revised: 16 September 2019 / Accepted: 5 October 2019 © The Author(s) 2019
Purpose 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. B
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Key points 1. Total Disc Replacements (TDR) are compromised by wear and parcle generaon 2. Metal wear parcles have not been characterised from spinal implants 3. Cobalt Chromium is an oen used biomaterial 4. Stainless steel is a biomaterial used in spinal implants 5. Glial cell responses to wear parcles from metallic biomaterials have not been invesgated to date
High resoluon scanning electron micrograph (SEM) of (A) CoCr parcles and (B) stainless steel parcles generated by pin-onplate wear simulaon; The effect of increasing volumes (0.5µm350µm3 per cell) of CoCr and stainless steel parcles on the viability of primary glial cells cultured together and in isolaon in 3D in culture over five days. Cell viability measured using a live/dead assay, mean percentage of living cells ± 95% confidence intervals. DMSO was used as a posive control. C) effect of CoCr parcles on astrocyte and microglial viability in co-culture, D) effect of CoCr parcles on astrocyt
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