title: Strategy towards independent electrical stimulation from cochlear implants: Guided auditory neuron growth on topographically modified nanocrystalline diamond.
abstract: 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 5×5μm(2)) 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 9μm. 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.
  
  
  CONCLUSIONS
  Cochlear implant is currently a successful way to treat sensorineural hearing loss and deafness especially in children. Although clinically successful, patients' fine hearing cannot be completely restored. One problem is the amount of the electrodes; 12-20 electrodes are used to replace the function of 3400 inner hair cells. Intense research is ongoing aiming to increase the number of electrodes. This study demonstrates the use of nanocrystalline diamond as a potential nerve-electrode interface. Micrometer-sized nanocrystalline diamond pillars showed high affinity to regenerated human neurons, which grew into a pre-defined network based on the pillar design. Our findings are of particular interest since they can be applied on any silicon-based implant to increase electrode count and to achieve individual neuron stimulation patterns.
authors.affiliation: Department of Engineering Sciences, Ångström Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Yixiao
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Otolaryngology and Head & Neck Surgery, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Edin
authors.affiliation: Physiology; Molecular Physiology and Neuroscience, Department of Neuroscience, Uppsala University, Uppsala, Sweden.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Jin
authors.affiliation: Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Andrei
authors.initials: A
authors.lastname: Alexsson
authors.affiliation: Neurosurgery, Department of Neuroscience, Uppsala University, Uppsala, Sweden.
authors.forename: Olafur
authors.initials: O
authors.lastname: Gudjonsson
authors.affiliation: Otolaryngology and Head & Neck Surgery, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Otolaryngology and Head & Neck Surgery, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Helge
authors.initials: H
authors.lastname: Rask-Andersen
authors.affiliation: Department of Engineering Sciences, Ångström Laboratory, Uppsala University, Uppsala, Sweden. Electronic address: mikael.karlsson@angstrom.uu.se.
authors.forename: Mikael
authors.initials: M
authors.lastname: Karlsson
authors.affiliation: Otolaryngology and Head & Neck Surgery, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden. Electronic address: hao.li@surgsci.uu.se.
authors.forename: Hao
authors.initials: H
authors.lastname: Li
mesh_terms: D000328:Adult; D000818:Animals; D001306:Auditory Pathways; D001369:Axons / Q000502:physiology; D002448:Cell Adhesion; D002713:Chlorine / Q000737:chemistry; D003054:Cochlear Implants; D003638:Deafness / Q000601:surgery; D018130:Diamond; D004558:Electric Stimulation; D004599:Electric Stimulation Therapy / Q000379:methods*; D004566:Electrodes; D004594:Electrophysiology; D005260:Female; D006309:Hearing; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D053758:Nanoparticles; D009474:Neurons / Q000166:cytology; D012038:Regeneration; D012825:Silicon / Q000737:chemistry; D013059:Spectrum Analysis, Raman; D013136:Spiral Ganglion / Q000502:physiology; D013234:Stem Cells / Q000166:cytology; D013701:Temporal Bone / Q000503:physiopathology
chemical_list: D002713:Chlorine; D018130:Diamond; D012825:Silicon
keywords: Axon guidance; Micro-textured surfaces; Nanocrystalline diamond; Neuron-electrode interface; Neuroregeneration