Fibrous tissue growth and loss of residual hearing after cochlear implantation can be reduced by application of the glucocorticoid dexamethasone-21-phosphate-disodium-salt (DEX). To date, sustained delivery of this agent to the cochlea using a number of pharmaceutical technologies has not been entirely successful. In this study we examine a novel way of continuous local drug application into the inner ear using a refillable hydrogel functionalized silicone reservoir. A PEG-based hydrogel made of reactive NCO-sP(EO-stat-PO) prepolymers was evaluated as a drug conveying and delivery system in vitro and in vivo. Encapsulating the free form hydrogel into a silicone tube with a small opening for the drug diffusion resulted in delayed drug release but unaffected diffusion of DEX through the gel compared to the free form hydrogel. Additionally, controlled DEX release over several weeks could be demonstrated using the hydrogel filled reservoir. Using a guinea-pig cochlear trauma model the reservoir delivery of DEX significantly protected residual hearing and reduced fibrosis. As well as being used as a device in its own right or in combination with cochlear implants, the hydrogel-filled reservoir represents a new drug delivery system that feasibly could be replenished with therapeutic agents to provide sustained treatment of the inner ear.

Dexamethasone (DEX) can reduce fibrous tissue growth as well as loss of residual hearing which may occur after cochlear implantation. Little is known about the effect of local inner ear DEX treatment on the spiral ganglion neurons (SGN), which are the target of the electrical stimulation with a cochlear implant (CI). Three different clinically relevant strategies of DEX-delivery into the inner ear were used. DEX was either eluted from the electrode carriers’ silicone, released from a reservoir by passive diffusion, or actively applied using a pump based system. The effect of the locally applied DEX on SGN density, size and function was evaluated. DEX did not affect the SGN density compared to the relevant control groups. Simultaneously applied with chronic electrical stimulation (ES), DEX increased the neuroprotective effect of ES in the basal region and the hearing threshold tended to decrease. The EABR thresholds did not correlate with the relevant SGN density. When correlating the SGN number with fibrosis, no dependency was observed. DEX concentrations as applied in these animal models are safe for inner ear delivery in terms of their effect on SGN density. Additionally, DEX tends to improve the neuroprotective effect of chronic electrical stimulation by increasing the number of surviving neurons. This is an important finding in regard to clinical applications of DEX for local treatment of the inner ear in view of cochlear implantation and other applications.

This study demonstrates UHV-alginate to be a suitable scaffold for BDNF-producing fibroblasts. UHV-alginates are a promising biomaterial for cochlear implant biofunctionalization.

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