**3. Discussion**

Formation of fibrous tissue around the electrode carrier after implantation remains one of the challenges in cochlear implantation. This increases electrical impedances at the stimulating contacts and can reduce the specificity of the stimulation and therefore potentially compromise the hearing outcome with a CI. Potentially induced trauma to the cochlea during electrode insertion and also a foreign body reaction are considered possible reasons for the tissue reaction. To address these, the current project aimed at the combination of a long-term release of DMS from the silicone body of the implant and a short-term release of other suitable substances from a coating on the surface of the electrode array. DCF and enalapril were identified as suitable substances as both are considered to reduce the inflammatory reaction and are already approved for other applications [23,25].

## *3.1. Cell Culture*

No substance applied to the inner ear should evoke toxic effects on spiral ganglion neurons. Therefore, both substances and DMS were first tested with freshly isolated SGN. Nearly no SGN survival at a concentration of 2 × 10−<sup>4</sup> mol/L and a slightly reduced survival at 4 × 10−<sup>5</sup> mol/L seem to indicate toxic effects at these concentrations. This can most likely be explained by the amount of solvent in the culture wells. DCF and DMS were dissolved in ethanol. Cell growth of HepG2 cells was strongly affected by an ethanol concentration of 2.5% [33], but the cytotoxic concentration differed depending on the cell type. As we had about 2% of ethanol in the samples with a substance concentration of 2 × 10−<sup>4</sup> mol/L, we speculate that the reduced cell survival can be attributed to the amount of ethanol in the wells. At lower concentrations, no differences compared to controls were detected for addition of DCF. Therefore, application of DCF is considered safe at least at concentrations of 4 × 10−<sup>5</sup> mol/L and below.

Enalapril was dissolved in DMSO. This led to a DMSO concentration of 0.28 mol/L in wells with an enalapril concentration of 2 × 10−<sup>4</sup> mol/L. A slightly reduced cell survival can be expected in the range of 0.4 mol/L DMSO in the wells for fibroblasts and the solvent has to be considered toxic at a concentration of 0.7 mol/L [34,35]. Therefore, we expect that neuronal survival at 2 × 10−<sup>4</sup> mol/L is most likely influenced by effects of the solvent. The DMSO concentration at 4 × 10−<sup>5</sup> mol/L was 0.056 mol/L. Therefore, and according to the published results, cell survival should nearly be unaffected [34,35]. Addition of enalapril never resulted in SGN survival above 80%. As survival of SGN with addition of enalapril was also different to controls at more concentrations, its application to the inner ear was considered not safe. Therefore, in all further experiments the focus was put on DCF.
