Preparation,Characterization And In Vitro/Vivo Evaluation Of A Dexamethasone/Poly(ε-Caprolactone)-based Electrode Coating For Cochlear Implants

Objective:Cochlear implantation is the main treatment for severe and extremely severe deafness.However,in the process of cochlear implantation,the cochlear electrodes will bring mechanical implantation trauma,lead to the injury of the intemal structure of the cochlea(such as spiral lamina,spiral ligament,basilar membrane,etc.),and cause inflammation in the cochlea,resulting in the formation of fibrous tissue in the cochlea,fibrosis and even ossification.Glucocorticoid as dexamethasone had been proved to be effective in the treatment of cochlear fibrosis caused by implantation truama,but the special anatomy of the inner ear makes it difficult to deliver drugs into the cochlea Therefore,this study is devoted to the preparation of a cochlear electrode drug delivery coating to control the cochlear fibrosis caused by cochlear implantation.Methods:The PCL electrode coating loaded with dexamethasone was prepared by dipping coating method.Through the optimization of different molecular weight PCL(Mn=2kDa,36kDa,60kDa.80kDa)and their ratio,the effect of PCL molecular weight on the properties of the coating was discussed.By optimizing the preparation process of impregnation conditions(such as impregnation time and dipping times),the thickness of PCL drug loading coating was adjusted,and the best preparation conditions of electrode coating suitable for cochlear implantation were selected,and the in vitro properties of the coating were characterized by scanning electron microscope,universal machine and high performance liquid chromatography(HPLC).Mouse fibroblast cells(L929)was co-cultured with the coating extract for 24 hours,and the biosafety of the coating in vitro was analyzed by CCK-8 test,and the local inflammatory reaction and scar hyperplasia of the tissue around the coating were observed through the experiment in rats and histopathology in vivo,so as to verify the biosafety performance of PCL coating in vivo.Results:The difference of molecular weight of PCL and the ratio of different molecular weight have no obvious effect on the thickness,surface morphology and drug release of the coating,but the Young’s modulus of PCL-DXM coating prepared by blending low molecular weight PCL and high molecular weight PCL is smaller than that of single molecular weight PCL coating.This that the mechanical properties of PCL-DXM electrode coating can be improved by blending PCL with different molecular weight The best preparation conditions of the selected coating are as follows:the number of impregnation is 1,the impregnation time is 10 seconds,and the concentration of PCL is 10%.The thickness of the prepared coating is uniform,and the average thickness is about 48.67 μm.Scanning electron microscope shows that there are micropores on the surface of the PCL coating,and the micropores of the low-high molecular weight blend coating are obviously smaller than those of the high molecular weight coating,and the surface smoothness is improved.And PCL drug-loaded coating can release dexamethasone slowly for a long time,and the drug concentration released in vitro can meet the needs of treatment The biosafety of the coating was good in vitro,and there was no significant difference between the experimental group(L929 cells co-incubated with coating extract for 24 hours)and the negative group(L929 cells co-incubated with sterile PBS solution for 24 hours).However,there was significant difference in cell activity between negative group(L929 cells co-incubated with sterile PBS solution for 24 hours)and positive group(L929 cells co-incubated with 0.2mg/mL cisplatin solution for 24 hours).The biological safety of the coating was good in vivo,and there was no obvious inflammatory reaction in the operation area.HE staining of the tissue around the implanted coating sample showed that there was no significant difference in trauma between the implanted coating and the implanted operation compared with the sham operation group.Conclusion:In summary,through the characterization of the coating and the study of the biosafety performance of the coating in vivo and in vitro,it is proved that PCL is an ideal controlled release material loaded with dexamethasone as a drug loading coating for cochlear implant electrode.therefore,PCL has broad application potential and prospect in cochlear implant electrode coating.