title: Guided growth of auditory neurons: Bioactive particles towards gapless neural - electrode interface.
abstract: 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 using125I-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 × 103M-1s-1and dissociation rate 2.6 × 10-5s-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.
authors.affiliation: Otolaryngology and Head & Neck Surgery, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Hao
authors.initials: H
authors.lastname: Li
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: Department of Otolaryngology, Gifu University, Gifu, Japan.
authors.forename: Hisamitsu
authors.initials: H
authors.lastname: Hayashi
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: Niklas
authors.initials: N
authors.lastname: Danckwardt-Lillieström
authors.affiliation: Applied Material Science, Department of Engineering Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Håkan
authors.initials: H
authors.lastname: Engqvist
authors.affiliation: Otolaryngology and Head & Neck Surgery, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden. Electronic address: Helge.Rask-andersen@surgsci.uu.se.
authors.forename: Helge
authors.initials: H
authors.lastname: Rask-Andersen
authors.affiliation: Applied Material Science, Department of Engineering Sciences, Uppsala University, Uppsala, Sweden. Electronic address: Wei.xia@angstrom.uu.se.
authors.forename: Wei
authors.initials: W
authors.lastname: Xia
mesh_terms: D000071437:Axon Guidance / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000008:administration & dosage / Q000737:chemistry; D003054:Cochlear Implants; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry; D009414:Nerve Growth Factors / Q000008:administration & dosage* / Q000737:chemistry; D016501:Neurites / Q000187:drug effects / Q000502:physiology*
chemical_list: D020099:Coated Materials, Biocompatible; D003692:Delayed-Action Preparations; D053769:Nanocapsules; D009414:Nerve Growth Factors
keywords: 3D culture; Bioactive spheres; Calcium phosphate; Cochlear implant; Neurotrophin