Potential new substances for reduction of fibrous tissue growth after cochlear implantation

Fibrous tissue growth around the cochlear implant electrode array remains one of the challenges related to cochlear implantation. Well known and in some parts also clinically used are corticosteroids. Searching literature, several other substances were identified with some potential to reduce inflammatory reactions and tissue growth. Amongst these substances are immunophilin inhibitors (some cyclosporine A derivatives lacking its immunosuppressive function), diclofenac and enalapril.

Immunophilin inhibitors MM284 and V20 as well as diclofenac and enalapril were tested for cytotoxicity on standard cell lines (NIH/3T3 fibroblasts) and fibroblasts from neonatal rat (P3-5) cochleae using MTT-Test and on freshly isolated spiral ganglion neurons (SGN). Cells were cultured in the presence of 10^-4 mol/l to 10^-12 mol/l of the test substance and compared to the known results of similar dexamethasone concentrations. The NIH/3T3 cells and the primary cochlear fibroblasts were cultured 24 hours before adding the substances for 48 hours and performing MTT tests. Substances were added to the seeded SGN for 48 hours in the respective concentrations before fixation and staining of the cells.

All substances (including dexamethasone) caused a reduced cell survival at a concentration of 10^-4 mol/l. From 10^-5 mol/l to 10^-12 mol/l, addition of dexamethasone, diclofenac and MM284 did not have an effect on the survival of any of the cells whereas V20 still showed a reduction in cell survival at 10^-5 mol/l. Cell survival after treatment with enalapril concentrations of 10^-7 mol/l or less was reduced compared to controls.

Therefore, immunophilin inhibitor MM284 and diclofenac are considered suitable candidates for further studies on reduction of inflammatory reaction after cochlear implantation.

Poster-PDF A-1699.PDF

Publication History

Article published online:
10 June 2020