Preparation,characterization And Preliminary Application Research Of A Sustained Dexamethasone Releasing Electrode Coating For Cochlear Implantation

BackgroundCochlear implantation has become the standard procedure of predominant treatment for patients suffering from profound sensorineural hearing loss.In recent years,electro-acoustic stimulation(EAS)increase further treatment opportunity for patient with residual hearing of low frequency.However,implantation trauma can trigger inflammation,fibrosis and ossification within the cochlea,and lead to residual hearing loss and make it difficult to reimplant.In current research,dexamethasone,as a typical representative of corticosteroids,was considered to reduce implantation trauma and postoperative inflammation and protect residual hearing effectively.But there are still many deficiencies in normal drug administration.MethodsPure hyaluronic acid was crosslinked with butanediol diglycidyl ether(BDDE).Artificial perilymph(APL)and dexamethasone sodium phosphate solution were then added to prepare the drug loading and cross-linked sodium hyaluronate hydrogel.One of the hydrogels was selected as preference based on their swelling behaviors.The rheological properties were explored and the hydrogel structure was analyzed by FT-IR and scan electron micrography(SEM).The technological parameters of the electrode coating are optimized with electrode coating process.The conductivity experiment was used to evaluate the electrical conductivity of preference hydrogel.The effect of electrode coating in reducing insertion force was also explored.The concentration of dexamethasone released in vitro experiment was detected by high-performance liquid chromatography(HPLC).The experimental study on biological safety was also explored with CCK-8 assay and Spiral Ganglion Neuron Explants culture.ResultsThe swelling ratio of hydrogels with different BDDE concentrations(2.0%,2.4%,2.8%3.2%,3.6%)was 14±0.31,11.5±0.31,10.15±0.29,9±0.38,8±0.31,respectively(P=0.000).Pure hyaluronic acid(HA)was crosslinked with butanediol diglycidyl ether(BDDE)and the successful preparation of the cross-linked sodium hyaluronate hydrogel(CHA)was confirmed by rheological characteristics and FTIR spectra.The morphological structure showed different sizes of porous structure among the cross-linked hydrogel,which providing structural basis for drug delivery.With different diameter of needle pecification,the uniform electrode coatings can be prepared by electrode coating process with different diameter of needle pecification base on the rheological characteristics of shear thinning.Capacity of electrode carrier is related to the syringe needle diameter.Therefore,Optimization of coating process was selected as follows:degree of 3.6vol%,pinhole diameter of 32G(110?m),pressure of 200±15.81 Psi(Pounds per square inch).The conductivities of UP-CHA,artificial perilymph,the crosslinking preferred hydrogel and commercially available hydrogel were 0.05±0.01 mS/cm,1.86±0.01 mS/cm,2.05±0.10 mS/cm,2.10±0.10 mS/cm,respectively.The results of insertion force experiment show that the coated electrode group has smaller average value of insertion force as compared with the uncoated electrode group.The drug release experiment in vitro shows that dexamethasone released from the drug loading hydrogel was 71.87±3.91%,317.66±20.87 mg/L after 1 week and 85.03±8.52%,104.61±30.27 mg/L after 20 days,lasting for 20 days.The experimental study on the biological safety in vitro showed that the cell survival rates of L929 fibroblasts in 12,24 and 48 hours for the selected hydrogel samples were 98.3%,98.5%and 98.6%respectively.Spiral ganglion neuron neurite bundle morphology,including density,length and number of neurite outgrowth density,almost has no difference between the control group and the preference hydrogel.ConclusionThe preference hydrogel electrode coating has great potential in preventing hearing loss and alleviating implantation trauma with good biocompatibility,approximate swelling ratio and conductivity,well simulation of ion homeostasis within the cochlear,properties of delivering dexamethasone for target anti-inflammatory,which shows a promising application in clinical practice.