Abstract
Despite the technological progress made with cochlear implants (CI), impedances and their diagnosis remain a focus of interest. Increases in impedance have been related to technical defects of the electrode as well as inflammatory and/or fibrosis along the electrode. Recent studies have demonstrated highly increased impedances as the result of corroded platinum (Pt) electrode contacts. This in vitro study examined the effects of Pt ions and compounds generated by corrosion of the electrode contacts of a human CI on cell metabolism. Since traces of solid Pt in surrounding cochlear tissues have been reported, the impact of commercially available Pt nanoparticles (Pt-NP, size 3 nm) on the cell culture model was also determined. For this purpose, the electrode contacts were electrically stimulated in a 0.5% aqueous NaCl solution for four weeks and the mass fraction of the platinum dissolute (Pt-Diss) was determined by mass spectrometry (ICP-MS). Metabolic activity of the murine fibroblasts (NIH 3T3) and the human neuroblastoma (SH-SY5Y) cells was determined using the WST-1 assay following exposure to Pt-Diss and Pt-NP. It was found that 5–50 μg/ml of the Pt-NP did not affect the viability of both cell types. In contrast, 100 μg/ml of the nanoparticles caused significant loss in metabolic activity. Furthermore, transmission electron microscopy (TEM) revealed mitochondrial swelling in both cell types indicating cytotoxicity. Additionally, TEM demonstrated internalized Pt-NP in NIH 3T3 cells in a concentration dependent manner, whereas endocytosis in SH-SY5Y cells was virtually absent. In comparison with the Pt-NP, the corrosion products (Pt-Diss) with concentrations between 1.64 μg/ml and 8.2 μg/ml induced cell death in both cell lines in a concentration dependent manner. TEM imaging revealed both mitochondrial disintegration and swelling of the endoplasmic reticulum, suggesting that Pt ions trigger cytotoxicity in both NIH 3T3 and SH-SY5Y cell lines by interacting with the respiratory chain.
Highlights
Cochlear implantation (CI) represents the only therapeutic intervention for patients with profound sensory neural hearing loss to date [1,2]
Determination of the effects of additional NaCl in the cell cultivation assay To exclude adverse effects of NaCl on cell growth and functionality cell culture assays containing medium with final NaCl concentrations of 6.26, 6.12 and 5.93 mg/ml were included in the investigation of potential cytotoxicity of Pt-containing dissolute (Pt-Diss)
We concluded that dilution of the culture medium with NaCl supplemention may limit the SH-SY5Y cell growth, but did not impair cell differentiation
Summary
Cochlear implantation (CI) represents the only therapeutic intervention for patients with profound sensory neural hearing loss to date [1,2]. Insertion of the CI into the scala tympani induces trauma in turn resulting in inflammation processes, fibrosis on the implant surface and new bone formation inside the scala tympani [3,4,5,6,7,8]. It was shown that those foreign-body reactions result in an increase of electrode impedance and in a decrease of the electrical dynamic range for stimulation. In cases of persistent high-impedance values neural response telemetry and reprogramming of the implant in conjunction with administration of cortisone and antibiotics usually lead to normalization of the impedance values. Several cases of recurrent increases in impedance in the same channels have been found which could not be explained by inflammation processes alone [13,14]. SEM micrographs of platinum microelectrodes demonstrated corrosion of Pt following stimulation in various biological buffer solutions [16]
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