Exogenous neurotrophin delivery to the deaf cochlea can prevent deafness-induced auditory neuron degeneration, however, we have previously reported that these survival effects are rapidly lost if the treatment stops. In addition, there are concerns that current experimental techniques are not safe enough to be used clinically. Therefore, for such treatments to be clinically transferable, methods of neurotrophin treatment that are safe, biocompatible and can support long-term auditory neuron survival are necessary. Cell transplantation and gene transfer, combined with encapsulation technologies, have the potential to address these issues. This study investigated the survival-promoting effects of encapsulated BDNF over-expressing Schwann cells on auditory neurons in the deaf guinea pig. In comparison to control (empty) capsules, there was significantly greater auditory neuron survival following the cell-based BDNF treatment. Concurrent use of a cochlear implant is expected to result in even greater auditory neuron survival, and provide a clinically relevant method to support auditory neuron survival that may lead to improved speech perception and language outcomes for cochlear implant patients.

This personal reflection outlines the discoveries at the University of Melbourne leading to the multi-channel cochlear implant, and its development industrially by Cochlear Limited. My earlier experimental electrophysiological research demonstrated temporal coding occurred for only low frequencies, i.e. below 200-500 pulses/second. I was able to confirm these findings perceptually in behaviourally conditioned animals. In addition, these studies showed that temporal discrimination occurred across spatial coding channels. These experimental results correlated with the later conscious experience for electrical stimulation in my implant patients. In addition, the mid-to-high frequencies were coded in part by place of stimulation using bipolar and monopolar stimulation to restrict current spread. Furthermore, place of stimulation had the qualities of sharpness and dullness, and was also experienced as vowels. Owing to the limitation in coding speech with a physiological model due to the overlap of electrical current leading to unpredictable variations in loudness, a speech coding strategy that extracted the most important speech features for transmission through an electro-neural 'bottle-neck' to the brain was explored. Our inaugural strategy, discovered in 1978, extracted the second formant for place of stimulation, voicing for rate of stimulation, and sound pressure for current level. This was the first coding strategy to provide open-set speech understanding, as shown by standard audiological tests, and it became the first clinically successful interface between the world and human consciousness. This strategy was improved with place coding for the third formant or high-frequency spectrum, and then the spectral maxima. In 1989, I operated on our first patient to receive a bilateral implant, and in 1990, the first with a bimodal processor. The psychophysics and speech perception for these showed that the stimuli from each side could be fused into a single image, and localized according to differences in intensity and time of arrival of the stimuli. There were significant improvements for speech perception in noise. In 1985, I implanted our first children with the multi-channel prosthesis and found that speech understanding and spoken language were greatly improved the younger the child at surgery, and especially when younger than 12 months. Speech understanding was strongly related to the development of place coding. In 1990, the US Food and Drug Administration approved the implant for deaf children, the first by any world health regulatory body making it the first major advance in helping deaf children to communicate.

In vivo host responses to an electrode-like array of aligned carbon nanotubes (ACNTs) embedded within a biopolymer sheet are reported. This biocompatibility study assesses the suitability of immobilized carbon nanotubes for bionic devices. Inflammatory responses and foreign-body histiocytic reactions are not substantially elevated when compared to negative controls following 12 weeks implantation. A fibrous capsule isolates the implanted ACNTs from the surrounding muscle tissue. Filamentous nanotube fragments are engulfed by macrophages, and globular debris is incorporated into the fibrous capsule with no further reaction. Scattered leukocytes are observed, adherent to the ACNT surface. These data indicate that there is a minimal local foreign-body response to immobilized ACNTs, that detached fragments are phagocytosed into an inert material, and that ACNTs do not attract high levels of surface fouling. Collectively, these results suggest that immobilized nanotube structures should be considered for further investigation as bionic components.

We have investigated the application of polypyrrole (pPy) as a material to influence neointimal cell behaviour. The physico-chemical properties of pPy doped with heparin (Hep), para-toluene sulfonate, poly(2-methoxyaniline-5-sulfonic acid) (pMAS) and nitrate ions were studied in addition to cell adhesion and proliferation studies of neointimal relevant cell lines cultured on the pPy substrates. Both smooth muscle (hSMC) and endothelial (hEC) cell types adhered and proliferated best on the smooth, hydrophilic pPy/pMAS material. Moreover, pPy/Hep is able to support the proliferation of hECs on the surface but inhibits hSMC proliferation after 4 days of culture. The inhibitory effect on hSMCs is most likely due to the well-known antiproliferative effect of heparin on hSMC growth. The results presented indicate that surface exposed heparin binds to the putative heparin receptor of hSMCs and is sufficient to inhibit proliferation. The application of galvanostatically synthesized pPy/Hep to stent surfaces presents a novel bioactive control mechanism to control neointimal cell growth.

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The multichannel cochlear implant is the first neural prosthesis to effectively and safely bring electronic technology into a direct physiological relation with the central nervous system and human consciousness. It is also the first cochlear implant to give speech understanding to tens of thousands of persons with profound deafness and spoken language to children born deaf in more than 80 countries. In so doing, it is the first major advance in research and technology to help deaf children communicate since Sign Language of the Deaf was developed at the Paris deaf school (L'Institut National de Jeunes Sourds de Paris) >200 years ago. Furthermore, biomedical research has been fundamental for ensuring that the multielectrode implant is safe as well as effective. More recent research has also shown that bilateral implants confer the benefits of binaural hearing. Future research using nanotechnology should see high-fidelity sound received, which would help deaf persons communicate in noise and enjoy music. Research should also lead to implants in ears with useful hearing.

A broader activation of auditory nerve fibres than normal using a cochlear implant contributes to poor frequency discrimination. As cochlear implants also deliver a restricted dynamic range, this hinders the ability to segregate sound sources. Better frequency coding and control over amplitude may be achieved by limiting current spread during electrical stimulation of the cochlea and positioning electrodes closer to the modiolus. Thin-film high density microelectrode arrays and conventional platinum ring electrode arrays were used to stimulate the cochlea of urethane-anaesthetized rats and responses compared. Neurophysiological recordings were taken at 197 multi-unit clusters in the central nucleus of the inferior colliculus (CIC), a site that receives direct monaural innervation from the cochlear nucleus. CIC responses to both the platinum ring and high density electrodes were recorded and differences in activity to changes in stimulation intensity, thresholds and frequency coding of neural activation were examined. The high density electrode array elicited less CIC activity at nonspecific frequency regions than the platinum ring electrode array. The high density electrode array produced significantly lower thresholds and larger dynamic ranges than the platinum ring electrode array when positioned close to the modiolus. These results suggest that a higher density of stimulation sites on electrodes that effectively 'aim' current, combined with placement closer to the modiolus would permit finer control over charge delivery. This may equate to improved frequency specific perception and control over amplitude when using future cochlear implant devices.

The restoration of hearing to persons with severely or profoundly impaired hearing by means of a cochlear implant is one of the great achievements of bionics applied to medicine. However, pneumococcal meningitis in implant recipients has received high profile public attention as a result of the US Food and Drug Administration's public health notification and recent media attention. Worldwide, 118 of the 60,000 people who received cochlear implants over the past 20 years have acquired meningitis, causing deep concern in the international medical community. This review provides answers to pediatricians, internists, and infectious diseases doctors who have patients with cochlear implants and who have questions about the safety of the cochlear implant from both the clinical and scientific research perspectives. Both clinical and laboratory research support the notion that pneumococcal meningitis is more likely in patients who receive cochlear implantation, and that the surgical insertion technique and the cochlear implant design should be nontraumatic, and that all cochlear implant recipients should be offered vaccination against Streptococcus pneumoniae.

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