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Guided Growth of Auditory Neurons: Bioactive Particles Towards Gapless Neural - Electrode Interface
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
Gifu Univ, Dept Otolaryngol, Gifu, Japan.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
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2017 (English)In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 122, 1-9 p.Article in journal (Refereed) Published
Abstract [en]

Cochlear implant (CI) is a successful device to restore hearing. Despite continuous development, frequency discrimination is poor in CI users due to an anatomical gap between the auditory neurons and CI electrode causing current spread and unspecific neural stimulation. One strategy to close this anatomical gap is guiding the growth of neuron dendrites closer to CI electrodes through targeted slow release of neurotrophins. Biodegradable calcium phosphate hollow nanospheres (CPHSs) were produced and their capacity for uptake and release of neurotrophins investigated using I-125-conjugated glia cell line-derived neurotrophic factor (GDNF). The CPHSs were coated onto CI electrodes and loaded with neurotrophins. Axon guidance effect of slow-released neurotrophins from the CPHSs was studied in an in vitro 3D culture model. CPHS coating bound and released GDNF with an association rate constant 6.3 x 10(3) M(-1)s(-1) and dissociation rate 2.6 x 10(-5) s(-1), respectively. Neurites from human vestibulocochlear ganglion explants found and established physical contact with the GDNF-loaded CPHS coating on the CI electrodes placed 0.7 mm away. Our results suggest that neurotrophin delivery through CPHS coating is a plausible way to close the anatomical gap between auditory neurons and electrodes. By overcoming this gap, selective neural activation and the fine hearing for CI users become possible.

Place, publisher, year, edition, pages
2017. Vol. 122, 1-9 p.
National Category
Medical and Health Sciences Engineering and Technology
Identifiers
URN: urn:nbn:se:uu:diva-276334DOI: 10.1016/j.biomaterials.2016.12.020ISI: 000394472500001PubMedID: 28107660OAI: oai:DiVA.org:uu-276334DiVA: diva2:909502
Funder
Swedish Research Council, 2013-5419
Available from: 2016-03-07 Created: 2016-02-11 Last updated: 2017-04-28Bibliographically approved
In thesis
1. Strategies in Cochlear Nerve Regeneration, Guidance and Protection: Prospects for Future Cochlear Implants
Open this publication in new window or tab >>Strategies in Cochlear Nerve Regeneration, Guidance and Protection: Prospects for Future Cochlear Implants
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Today, it is possible to restore hearing in congenitally deaf children and severely hearing-impaired adults through cochlear implants (CIs). A CI consists of an external sound processor that provides acoustically induced signals to an internal receiver. The receiver feeds information to an electrode array inserted into the fluid-filled cochlea, where it provides direct electrical stimulation to the auditory nerve. Despite its great success, there is still room for improvement, so as to provide the patient with better frequency resolution, pitch information for music and speech perception and overall improved quality of sound.

 A better stimulation mode for the auditory nerves by increasing the number of stimulation points is believed to be a part of the solution. Current technology depends on strong electrical pulses to overcome the anatomical gap between neurons and the CI. The spreading of currents limits the number of stimulation points due to signal overlap and crosstalk.

Closing the anatomical gap between spiral ganglion neurons and the CI could lower the stimulation thresholds, reduce current spread, and generate a more discrete stimulation of individual neurons. This strategy may depend on the regenerative capacity of auditory neurons, and the ability to attract and guide them to the electrode and bridge the gap.

Here, we investigated the potential of cultured human and murine neurons from primary inner ear tissue and human neural progenitor cells to traverse this gap through an extracellular matrix gel.

Furthermore, nanoparticles were used as reservoirs for neural attractants and applied to CI electrode surfaces. The nanoparticles retained growth factors, and inner ear neurons showed affinity for the reservoirs in vitro.

The potential to obtain a more ordered neural growth on a patterned, electrically conducting nanocrystalline diamond surface was also examined. Successful growth of auditory neurons that attached and grew on the patterned substrate was observed.

By combining the patterned diamond surfaces with nanoparticle-based reservoirs and nerve-stimulating gels, a novel, high resolution CI may be created. This strategy could potentially enable the use of hundreds of stimulation points compared to the 12 – 22 used today. This could greatly improve the hearing sensation for many CI recipients. 

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. 56 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1193
Keyword
Human vestibular nerve, Scarpa's ganglion, Stem cells, Nanoparticles, Nanocrystalline diamond
National Category
Medical and Health Sciences Basic Medicine
Research subject
Oto-Rhino-Laryngology; Medical Science
Identifiers
urn:nbn:se:uu:diva-276336 (URN)978-91-554-9503-9 (ISBN)
Public defence
2016-04-28, Skoogsalen, Akademiska Sjukhuset, Ingång 78/79, Uppsala, 09:00 (English)
Opponent
Supervisors
Available from: 2016-04-07 Created: 2016-02-11 Last updated: 2016-04-12

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Li, HaoEdin, FredrikGudjonsson, OlafurDanckwardt-Lillieström, NiklasEngqvist, HåkanRask-Andersen, HelgeXia, Wei

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