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 using I-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 × 10 Ms and dissociation rate 2.6 × 10 s, 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.

Long-term delivery of brain-derived neurotrophic factor (BDNF) from nanoporous silica nanoparticles improves the survival of spiral ganglion neurons in vitro

“…When a cochlear implant is placed anyway, the incorporation of a delivery system seems very appropriate. Released BDNF can then act as a neuroprotective factor and might guide neurite outgrowth towards the cochlear electrode [ 37 , 45 , 57 ].…”

Interaction of micropatterned topographical and biochemical cues to direct neurite growth from spiral ganglion neurons

“…For this to occur, neurite regeneration must first be stimulated. Several groups have demonstrated that neurotrophic factors, such as BDNF and NT-3, are sufficient to induce SGN neurite regeneration in vivo following deafening (Budenz et al, 2015; H. Li et al, 2017; Shibata et al, 2010; Wise et al 2005).…”

“…Li et al, 2017; Shibata et al, 2010; Wise et al 2005). Further, gradients of neurotrophic factors have been shown to guide SGN neurite growth in vitro (H. Li et al, 2017).…”

“…Li et al, 2017). Once neurite regeneration has been stimulated, scaffoldings engineered to guide neurite growth could then be deployed to ensure that the neurite growth remains organized and is directed towards intended targets (Ceschi et al, 2014; H. Li et al, 2017).…”

Detecting ligand interactions in real time on living bacterial cells

“…This results in a reference-subtracted real-time binding curve that provides information about the affinity, kinetics, and possibly also the binding mechanisms of the interaction between the ligand and the cells within the target area. The LigandTracer instrument series have previously been used in an increasing number of studies (> 70 papers as of August 2017), primarily with protein ligands and living mammalian cells expressing target receptors, but alternative ligands and targets are possible, such as small molecular drugs, nanoparticles, and antigens on magnetic beads (Björkelund et al 2011 ; Pa̧zik et al 2011 ; Mihaylova et al 2014 ; Li et al 2017 ; Zeilinger et al 2017 ; Bugaytsova et al 2017 ). A major requirement for the use of the LigandTracer instrument is the necessity to immobilize cells or the isolated receptor on the surface of a regular Petri dish.…”