Doctor of Philosophy
School of Chemistry
Thompson, Brianna C., The controlled release of neurotrophic proteins from the conducting polymer polypyrrole to improve the nerve/cochlear implant interface, Doctor of Philosophy thesis, School of Chemistry, University of Wollongong, 2009. http://ro.uow.edu.au/theses/3067
The cochlear implant has restored hearing to hundreds of thousands of profoundly deaf individuals since the early 1980s. The implant works by providing electrical stimulation directly to the auditory nerves, bypassing the damaged sensory processes. As the electrodes of the cochlear implant are required to directly stimulate the auditory nerves, the interface between these electrodes and the nervous system is a vital part of the function of the bionic device. However, in cases of long-term hearing loss the auditory nerve degenerates and auditory nerve processes, or neurites, retract away from the cochlea and the intra-cochlear electrodes. This leads to a loss of effectiveness cochlear implant. Currently the only remedy for this probleme is to amplify the electrical signals provided to the implant, but this causes shorter battery life due to the higher currents and voltages and can potentially be damaging to the tissues in and surrounding the cochlea. This work describes attempts to develop a material which can be coated onto cochlear electrodes to preserve auditory nerves, potentially improving the interface between the cochlear implant and the auditory nerve. The material used throughout this work, polypyrrole, is a conducting polymer. Due to its unique properties, polypyrrole can be used to incorporate and release charged molecules with different electrical stimuli. The work presented within this thesis describes the development of polypyrrole to release nerve growth factors, which are also known as neuortrophins, in order to improve auditory nerve survival and growth. With delivery of nerve growth factor in response to the electrical stimuli provided by the cochlear implant, it is hoped that better nerve survival will lead to an improved nerve/cochlear electrode interface, and better function of the implant. Extensive tests on the release of radiolabelled neurotrophins from polypyrrole substrates were performed under a variety of conditions in order to optimise both the material and the electrical stimulation used for controlled release. The focus of most work was neurotrophin-3, the member of the neurotrophin family of proteins that has the most widespread action on cell receptors. Testing of the response of auditory nerve tissue dissected from rats showed that neurotrophins released from polypyrrole promoted the survival and growth of nerves in vitro. From these experiments, it was determined that electrical stimulation was effective in controlling the release of neurotrophins to improve neurite outgrowth to a significant degree. Based on these results in vivo experiments were undertaken, in which guinea pigs were implanted with cochlear electrodes coated with polypyrrole. From these experiments, it was determined that electrical stimulation to promote neurotrophin release helped not only to prevent implantation trauma, but also to prevent deafening-related degeneration of auditory nerves observed in untreated cochleae. Additionally, some further optimisation of the materials was completed. Another neurotrpohin, brain derived neurotrophic factor, has been shown to work synergistically with neurotrophin-3, and the release of both neurotrophins from a single polypyrrole film was investigated. While the release of the proteins was not as well controlled, the effect of release on auditory nerve explants cultured in vitro was significantly greater than either neurotrophin alone. Studies exploring release of neurotrophin-3 from PPy coated on several novel substrates were performed, suggesting that biodegradable and nanostructured materials can be used to further tailor the release of therapeutic proteins from polypyrrole. An implantable power source - a biobattery - was also used to electrically control the release of neurotrophin-3, highlighting the potential for a totally implantable system for the controlled release of therapeutic molecules using the polypyrrole materials developed. The insights gained in the course of this work may have implications for the controlled release of other therapeutic molecules from polypyrrole. Additionally, the information contained within this thesis could also have relevance beyond the scope of the cochlear implant/neural interface, with potential for use in other bionic devices or in nerve repair applications. The work described here demonstrates the potential to enhance nerve/ electrode interfaces using polypyrrole to electrically control the release neurotrophins.
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