Living electrodes for auditory rehabilitation.

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Hearing loss affects over 28 million Americans and is the second most common disability in the Veteran population. For hearing loss too severe to be helped by hearing aids, cochlear implants have become the standard of care. Though they can restore the ability to understand speech for many, current electrodes have poor selectivity for neuronal excitation. This limits fidelity leading to difficulty with background noise, talking on the phone, and music appreciation. Researchers at the Center for Neurotrauma, Neurodegeneration, and Restoration (CNNR) at the CMC-VAMC have pioneered biologically-based neural interfaces with neuron- specific stimulation that have yet to be applied to hearing restoration. This project utilizes transplantable living scaffolds for the rehabilitation of hearing through biohybrid neural interfaces. Biohybrid neural interfaces will be developed that allow transplanted spiral ganglion neurons (SGN) to remain accessible to stimulation while their axons interact with neurons of the central auditory pathway or cochlea – creating a “living electrode”. SGN will be harvested from neonatal rat temporal bones and the cells’ ability to stimulate a distinct population of SGN (cochlear implantation), and centrally derived neurons (brainstem implantation) will be confirmed in culture. Light activated opsins will also be induced to allow for optical stimulation. SGNs will then be grown on two distinct scaffolds in vitro. The first directs transplanted SGN axons to the inferior colliculus in the brainstem, and the second directs them from the round window of the cochlea to the native spiral ganglion. Both designs allow for electric and optical stimulation of the transplanted SGN cell bodies. Once transplanted into living rats, cell survival and integration are evaluated with immunohistochemistry at various timepoints for up to 6 months. Electrophysiologic recordings from the auditory cortex will be obtained in deafened rats implanted with either the brainstem or cochlear scaffolds, while being stimulated either electrically or optically. Behavioral models will then used to evaluate the auditory perception induced via stimulation of the living scaffolds. The final product of this project will be two form-factors of living electrodes for hearing rehabilitation, one for implantation into the inferior colliculus and one for implantation into the cochlea. It is expected that the neuron- specific simulation permitted by this technique will allow for precision in stimulation of the auditory system that cannot be approached by current implant technology. This is a resubmission of a new proposal. This work is directly translatable to improved implantable hearing devices for those with hearing loss too severe to be adequately rehabilitated with traditional hearing aids. Improvement in the rehabilitative options for these veterans will have a significant impact on their quality of life and well-being. Not only does the proposed work advance a next generation, biologically based interface to restore the ability to interpret sophisticated auditory inputs in our Veterans, as a Career Development Award, it will also serve as vehicle to expand my technical skills in tissue engineering and regenerative therapies. This CDA will form the foundation of a career in pushing the boundaries of hearing restoration.