A new paradigm of hearing loss and preservation with cochlear implants: Learnings from fundamental studies and clinical research.

In 2010 Cochlear initiated a coordinated preclinical research program to identify the factors and underlying mechanisms of acoustic hearing loss following cochlear implantation and device use. At its inception the program was structured around several major hypotheses implicated in the loss of acoustic hearing. The understanding of causes evolved over the course of the program, leading to an increased appreciation of the role of the biological response in post-implant hearing loss. A systematic approach was developed which mapped the cochlear implant journey along a timeline that considers all events in an individual's hearing history. By evaluating the available data in this context, rather than by discrete hypothesis testing, causative and associated factors may be more readily detected. This approach presents opportunities for more effective research management and may aid in identifying new prospects for intervention. Many of the outcomes of the research program apply beyond preservation of acoustic hearing to factors important to overall cochlear health and considerations for future therapies.

Effects of chronic implantation and long-term stimulation of a cochlear implant in the partial hearing cat model.

The expansion of criteria for cochlear implantation has resulted in increasing numbers of cochlear implant subjects having some level of residual hearing. The present study examined the effects of implantation surgery and long-term electrical stimulation on residual hearing in a partially deafened cat model. Eighteen animals were partially deafened, implanted and chronically stimulated. Implantation resulted in a pronounced loss evident 2-weeks post implantation of up to 30-40 dB at 4 & 8 kHz which was statistically significant (2-way RM ANOVA (Time, Frequency): p(Time) = 0.001; p(Frequency) < 0.001; p(Time x Frequency) < 0.001)). Chronic stimulation resulted in a significant (RM ANOVA: p(Time) = 0.030) ongoing hearing loss, with 5 animals (∼30%) exhibiting an increase in threshold of 20 dB or more. Different loss profiles were evident with peripheral and central hearing assessments suggests that changes in 'central gain' may be occurring. Despite significant loss of hair cells and spiral ganglion neurons and distinct fibrous tissue growth in the scala tympani following implantation and long-term electrical stimulation, there were no significant correlations with any histological measures and ongoing hearing loss. The partially deafened, chronically stimulated cat model provides a clinically relevant model in which to further investigate the cause of the delayed hearing loss following cochlear implant surgery and use.

A mouse model of cochlear implantation with chronic electric stimulation.

OBJECTIVES: Cochlear implants provide an effective treatment option for those with severe hearing loss, including those with preserved low frequency hearing. However, certain issues can reduce implant efficacy including intracochlear tissue response and delayed loss of residual acoustic hearing. We describe a mouse model of cochlear implantation with chronic electric stimulation that can be used to study cochlear implant biology and related pathologies. METHODS: Twelve normal hearing adult CBA/J mice underwent unilateral cochlear implantation and were evenly divided into one group receiving electric stimulation and one not. Serial impedance and neural response telemetry (NRT) measurements were made to assess implant functionality. Functionality was defined as having at least one electrode with an impedance ≤ 35 kOhms. Mouse cochleae were harvested for histology and 3D x-ray microscopy 21 days post-operatively, or, in case the implant was still functional, at a later time point when the implant failed. A separate experiment measured the hearing preservation rate in 7 adult CBA/J mice undergoing unilateral cochlear implantation with serial auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE). RESULTS: Implants maintained functionality for a mean of 35 days in the non-stimulated group and 19.8 days in the stimulated group. Reliable NRT and behavioral responses to electric stimulation were recorded. A robust intracochlear peri-implant tissue response with neo-ossification was seen in all cochleae. Six of seven mice maintained intact low frequency hearing up to 6 weeks following cochlear implantation. CONCLUSIONS: We demonstrate the feasibility of cochlear implantation and behaviorally significant electric stimulation in the mouse, with the potential for hearing preservation. This model may be combined with established mouse models of hearing loss and the large genetic and molecular research toolkit unique to the mouse for mechanistic and therapeutic investigations of cochlear implant biology.

Improving cochlear implant properties through conductive hydrogel coatings.

Conductive hydrogel (CH) coatings for biomedical electrodes have shown considerable promise in improving electrode mechanical and charge transfer properties. While they have desirable properties as a bulk material, there is limited understanding of how these properties translate to a microelectrode array. This study evaluated the performance of CH coatings applied to Nucleus Contour Advance cochlear electrode arrays. Cyclic voltammetry and biphasic stimulation were carried out to determine electrical properties of the coated arrays. Electrical testing demonstrated that CH coatings supported up to 24 times increase in charge injection limit. Reduced impedance was also maintained for over 1 billion stimulations without evidence of delamination or degradation. Mechanical studies performed showed negligible effect of the coating on the pre-curl structure of the Contour Advance arrays. Testing the coating in a model human scala tympani confirmed that adequate contact was maintained across the lateral wall. CH coatings are a viable, stable coating for improving electrical properties of the platinum arrays while imparting a softer material interface to reduce mechanical mismatch. Ultimately, these coatings may act to minimize scar tissue formation and fluid accumulation around electrodes and thus improve the electrical performance of neural implants.

Integrated electrode and high density feedthrough system for chip-scale implantable devices.

High density feedthroughs have been developed which allow for the integration of chip-scale features and electrode arrays with up to 1141 stimulating sites to be located on a single implantable package. This layered technology displays hermetic properties and can be produced from as little as two laminated 200 µm thick alumina sheets. It can also be expanded to a greater number of layers to allow flexible routing to integrated electronics. The microelectrodes, which are produced from sintered platinum (Pt) particulate, have high charge injection capacity as a result of a porous surface morphology. Despite their inherent porosity the electrodes are electrically stable following more than 1.8 billion stimulation pulses delivered at clinically relevant levels. The ceramic-Pt constructs are also shown to have acceptable biological properties, causing no cell growth inhibition using standard leachant assays and support neural cell survival and differentiation under both passive conditions and active electrical stimulation.