Novel Methods to Promote Survival and Regeneration of the Auditory Nerve and Improve Cochlear Implant Function.

A principal cause of sensorineural hearing loss is injury to or loss of cochlear hair cells, which are critical components of sound transduction. These auditory hair cells do not naturally regenerate in mammals. Loss of hair cells often leads to a degeneration of the processes that innervate them along with the ganglion cell bodies of the auditory nerve. The only currently accepted treatment for hearing loss of this type is the cochlear implant, an auditory prosthesis that has been in clinical use for over 30 years. While the cochlear implant has been successful in providing or restoring hearing to over 100,000 patients, there are limitations to the hearing provided by the implant, particularly for complex sounds such as speech in noise and music. The peripheral processes and ganglion cell bodies receive and process the electrical stimulation from the implant, and thus the survival of these components of the auditory nerve is critical to the perception of sound from the cochlear implant. This dissertation presents two novel methods of promoting auditory nerve survival and regrowth following hair cell loss. The first method used an adenoviral construct containing a gene insert for brain – derived neurotrophic factor, designed to increase endogenous production of this growth factor. The introduction of this adenovirus into the cochlea led to a decrease in electrophysiological and psychophysical thresholds to cochlear implant stimulation and promoted long – term ganglion cell survival. This study was unique in addressing the psychophysical effects of the anatomical changes induced by growth factor treatment. In the second method, a specialized implant coating was designed to attract growth of peripheral processes to make contact with a cochlear implant in vivo. In this study, a new histological technique was developed, which allowed visualization of peripheral processes and evaluation of their spatial relationship with an implant. This coating attracted significant neuronal growth in close proximity to the implant and decreased the impedance between implant electrodes. These studies together demonstrate the significant plasticity of the auditory nerve to survive following deafness, and indicate the potential for nerve regeneration efforts to improve cochlear implant performance.Ph.D.NeuroscienceUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/62248/1/jchikar_1.pd

Organic electrode coatings for next-generation neural interfaces

Traditional neuronal interfaces utilize metallic electrodes which in recent years have reached a plateau in terms of the ability to provide safe stimulation at high resolution or rather with high densities of microelectrodes with improved spatial selectivity. To achieve higher resolution it has become clear that reducing the size of electrodes is required to enable higher electrode counts from the implant device. The limitations of interfacing electrodes including low charge injection limits, mechanical mismatch and foreign body response can be addressed through the use of organic electrode coatings which typically provide a softer, more roughened surface to enable both improved charge transfer and lower mechanical mismatch with neural tissue. Coating electrodes with conductive polymers or carbon nanotubes offers a substantial increase in charge transfer area compared to conventional platinum electrodes. These organic conductors provide safe electrical stimulation of tissue while avoiding undesirable chemical reactions and cell damage. However, the mechanical properties of conductive polymers are not ideal, as they are quite brittle. Hydrogel polymers present a versatile coating option for electrodes as they can be chemically modified to provide a soft and conductive scaffold. However, the in vivo chronic inflammatory response of these conductive hydrogels remains unknown. A more recent approach proposes tissue engineering the electrode interface through the use of encapsulated neurons within hydrogel coatings. This approach may provide a method for activating tissue at the cellular scale, however, several technological challenges must be addressed to demonstrate feasibility of this innovative idea. The review focuses on the various organic coatings which have been investigated to improve neural interface electrodes