Support is requested for the development of improvements to the cochlear prosthesis or cochlear implant. The cochlear implant employs electrical stimulation to activate auditory neurons in patients that have lost their hearing due to the death of inner ear sensory cells. This device is now widely used to treat the deaf, and is increasingly used for patients with residual hearing. It provides substantial benefit for both populations, but the performance of even the most successful patients is far lower than that achieved by normal hearing listeners. The proposed research program is designed to improve the cochlear implant by combining device engineering and biological approaches. RESEARCH DESIGN: Performance will be enhanced by decreasing the distance between the electrodes and cochlear neurons, so that more channels of information can be delivered, by increasing the survival of cochlear neurons, and by maintaining the neurons in contact with the implant. These goals will be achieved by producing a biological interface between the implant and the tissues of the inner ear. The prior research of this program has used primarily in vitro methods to identify factors that regulate the growth of cochlear nerve fibers and enhance neuronal survival; to evaluate the growth of neurites through three-dimensional substrates that might link a cochlear implant to the region of the spiral ganglion, and to evaluate the growth of inner ear nerve fibers on implant materials. In this application, we propose to transfer these in vitro results to the in vivo situation, using an animal model of complete sensory cell loss. This includes efficacy and materials compatibility studies, exploration of techniques to enhance growth of nerve fibers out of the spiral ganglion, and evaluation of titanium as a stable neuronal attachment and survival medium. METHODOLOGY: Guinea pigs will be deafened by the application of ototoxins. They will then be implanted with cochlear implants surrounded by hydrogels in which microchannels have been engineered to lead from the cochlear ganglion to the implant. Osmotic minipumps, cells engineered to produce neurotrophins, and layer-by-layer thin films that mediate slow release of neurotrophins, will be used to attract cochlear neuron fibers into the microchannels and to the implant. Surface engineered titanium will be used to maintain nerve fibers at the implant and enhance their survival. CLINICAL RELATIONSHIP: Disorders of hearing and balance, including SNHL, tinnitus, balance disorders and middle ear infections, are major health problems for Veterans, often resulting from damage to the ear as a consequence of military service and deployment. Future studies will include experiments with human tissue, development of a clinical device, and clinical trials. The general principles that will be studied in this program wll also be applicable to other health problems of Veterans. Improved interfaces between electrode arrays and neurons could also be applied to Veterans with visual deficits and in spinal cord injury.

Public Health Relevance

Sensorineural hearing loss (SNHL) is an extremely common disability in the Veteran population and exposure to noise associated with military service frequently leads to service-related hearing disorders; moreover, this risk is increasing rapidly, because the degree and nature of military noise exposure has changed and because SNHL is a frequent consequence of blast exposure. Therefore, an unfortunately high percentage of the personnel returning from duty in the Middle East have evidence of SNHL. The cost to the VA of disability payments for hearing disorders currently exceeds 1.6 billion dollars/year. A treatment for severe total or high-frequency hearing loss is the cochlear implant, which stimulates surviving cochlear neurons, but this device does not restore normal hearing. This project is designed to improve device function by attracting the processes of cochlear neurons to the device, maintaining neuronal contacts with the device, and increasing neuronal survival, when enhancing rehabilitation of Veterans with SNHL.

National Institute of Health (NIH)
Veterans Affairs (VA)
Non-HHS Research Projects (I01)
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Rehabilitation Engineering & Prosthetics/Orthotics (RRD5)
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VA San Diego Healthcare System
San Diego
United States
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Deniffel, Dominik; Nuyen, Brian; Pak, Kwang et al. (2017) Otitis Media and Nasopharyngeal Colonization in ccl3-/- Mice. Infect Immun 85:
Taura, A; Taura, K; Koyama, Y et al. (2016) Hair cell stereociliary bundle regeneration by espin gene transduction after aminoglycoside damage and hair cell induction by Notch inhibition. Gene Ther 23:415-23
Hernandez, Michelle; Leichtle, Anke; Pak, Kwang et al. (2015) The transcriptome of a complete episode of acute otitis media. BMC Genomics 16:259
Froud, Kristina E; Wong, Ann Chi Yan; Cederholm, Jennie M E et al. (2015) Type II spiral ganglion afferent neurons drive medial olivocochlear reflex suppression of the cochlear amplifier. Nat Commun 6:7115
Wong, Ann C Y; Ryan, Allen F (2015) Mechanisms of sensorineural cell damage, death and survival in the cochlea. Front Aging Neurosci 7:58
Brand, Yves; Sung, Michael; Pak, Kwang et al. (2015) Neural cell adhesion molecule NrCAM is expressed in the mammalian inner ear and modulates spiral ganglion neurite outgrowth in an in vitro alternate choice assay. J Mol Neurosci 55:836-44
Sung, Michael; Wei, Eric; Chavez, Eduardo et al. (2014) Inhibition of MMP-2 but not MMP-9 influences inner ear spiral ganglion neurons in vitro. Cell Mol Neurobiol 34:1011-21
Euteneuer, Sara; Yang, Kuo H; Chavez, Eduardo et al. (2013) Glial cell line-derived neurotrophic factor (GDNF) induces neuritogenesis in the cochlear spiral ganglion via neural cell adhesion molecule (NCAM). Mol Cell Neurosci 54:30-43