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Strategy towards independent electrical stimulation from cochlear implants: Guided auditory neuron growth on topographically modified nanocrystalline diamond
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
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 Neuroscience, Physiology. (Molekylär fysiologi och neurovetenskap)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
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2016 (English)In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 31, 211-220 p.Article in journal (Refereed) Published
Abstract [en]

Cochlear implants (CI) have been used for several decades to treat patients with profound hearing loss. Nevertheless, results vary between individuals, and fine hearing is generally poor due to the lack of discrete neural stimulation from the individual receptor hair cells. A major problem is the deliverance of independent stimulation signals to individual auditory neurons. Fine hearing requires significantly more stimulation contacts with intimate neuron/electrode interphases from ordered axonal re-growth, something current CI technology cannot provide.

Here, we demonstrate the potential application of micro-textured nanocrystalline diamond (NCD) surfaces on CI electrode arrays. Such textured NCD surfaces consist of micrometer-sized nail-head-shaped pillars (size 5 5 lm2) made with sequences of micro/nano-fabrication processes, including sputtering, photolithography and plasma etching.

The results show that human and murine inner-ear ganglion neurites and, potentially, neural progenitor cells can attach to patterned NCD surfaces without an extracellular matrix coating. Microscopic methods revealed adhesion and neural growth, specifically along the nail-head-shaped NCD pillars in an ordered manner, rather than in non-textured areas. This pattern was established when the inter-NCD pillar distance varied between 4 and 9 lm.

The findings demonstrate that regenerating auditory neurons show a strong affinity to the NCD pillars, and the technique could be used for neural guidance and the creation of new neural networks. Together with the NCD’s unique anti-bacterial and electrical properties, patterned NCD surfaces could provide designed neural/electrode interfaces to create independent electrical stimulation signals in CI electrode arrays for the neural population.

Place, publisher, year, edition, pages
2016. Vol. 31, 211-220 p.
National Category
Medical Materials Engineering and Technology
Identifiers
URN: urn:nbn:se:uu:diva-266956DOI: 10.1016/j.actbio.2015.11.021ISI: 000370086100019PubMedID: 26593784OAI: oai:DiVA.org:uu-266956DiVA: diva2:871463
Funder
EU, FP7, Seventh Framework Programme, 603029
Available from: 2015-11-14 Created: 2015-11-14 Last updated: 2017-12-01Bibliographically 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: 2018-01-10
2. Bio-Nano Interactions: Synthesis, Functionalization and Characterization of Biomaterial Interfaces
Open this publication in new window or tab >>Bio-Nano Interactions: Synthesis, Functionalization and Characterization of Biomaterial Interfaces
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Current strategies for designing biomaterials involve creating materials and interfaces that interact with biomolecules, cells and tissues.  This thesis aims to investigate several bioactive surfaces, such as nanocrystalline diamond (NCD), hydroxyapatite (HA) and single crystalline titanium dioxide, in terms of material synthesis, surface functionalization and characterization.

Although cochlear implants (CIs) have been proven to be clinically successful, the efficiency of these implants still needs to be improved. A CI typically only has 12-20 electrodes while the ear has approximately 3400 inner hair cells. A type of micro-textured NCD surface that consists of micrometre-sized nail-head-shaped pillars was fabricated. Auditory neurons showed a strong affinity for the surface of the NCD pillars, and the technique could be used for neural guidance and to increase the number of stimulation points, leading to CIs with improved performance.

Typical transparent ceramics are fabricated using pressure-assisted sintering techniques. However, the development of a simple energy-efficient production method remains a challenge. A simple approach to fabricating translucent nano-ceramics was developed by controlling the morphology of the starting ceramic particles. Translucent nano-ceramics, including HA and strontium substituted HA, could be produced via a simple filtration process followed by pressure-less sintering. Furthermore, the application of such materials as a window material was investigated. The results show that MC3T3 cells could be observed through the translucent HA ceramic for up to 7 days. The living fluorescent staining confirmed that the MC3T3 cells were visible throughout the culture period.

Single crystalline rutile possesses in vitro bioactivity, and the crystalline direction affects HA formation. The HA growth on (001), (100) and (110) faces was investigated in a simulated body fluid in the presence of fibronectin (FN) via two different processes. The HA layers on each face were analysed using different characterization techniques, revealing that the interfacial energies could be altered by the pre-adsorbed FN, which influenced HA formation.

In summary, micro textured NCD, and translucent HA and FN functionalized single crystalline rutile, and their interactions with cells and biomimetic HA were studied. The results showed that controlled surface properties are important for enhancing a material’s biological performance.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. 37 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1345
Keyword
Bioactive surfaces, nanocrystalline diamond, hydroxyapatite, protein secondary structure, protein absorption, auditory neurons, single crystalline rutile, nano morphology, surface functionalisation, in vitro biomineralisation, translucent nano-ceramics, bio-window material, material characterisation.
National Category
Engineering and Technology
Research subject
Engineering Science with specialization in Materials Science
Identifiers
urn:nbn:se:uu:diva-277121 (URN)978-91-554-9478-0 (ISBN)
Public defence
2016-06-01, Häggsalen, Ångströmlaboratoriet, Lägerhyddsvägen 1, Uppsala, 10:15 (English)
Opponent
Supervisors
Available from: 2016-05-11 Created: 2016-02-17 Last updated: 2016-06-01

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Cai, YixiaoEdin, FredrikJin, ZheAlexsson, AndreiGudjonsson, OlafurLiu, WeiRask-Andersen, HelgeKarlsson, MikaelLi, Hao

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