Neurite regeneration of auditory neurons using NT3 in a neurite outgrowth chamber for improvement of the nerve-electrode interface

Introduction

A direct link between cochlear implant (CI) electrode and neurons of the auditory nerve (spiral ganglion neurons) is expected to improve the focused stimulation of the nerve and thus the speech perception. One opportunity to bridge the distance between the electrode in the scala tympani (ST) and the neurons in the Rosenthal’s canal (RC) is a guided regeneration of the neurites towards the implant e.g. by growth factor treatment. Neurotrophin 3 (NT3) is a promising candidate for this application and was tested by pump-delivery in an inner ear mimicking cell culture chamber (neurite outgrowth chamber, NOC) on spiral ganglion explants (SGE) in this study.

Methods

The NOC was 3D-printed from polylactic acid (PLA) and included two interconnected compartments: ST-comp for factor release by mini-osmotic pump and RC-comp for cultivation of SGE. The pumps delivered NT3 (750 ng/ml, 0,5 µl/h) or artificial perilymph as negative control (NC) for 14 days and one NOC with SGE was connected to the pump for 4 days per week and cultivated with or without medium change. Subsequently, neurite outgrowth was analyzed.

Results

The 14-day release of NT3 via pump induced an increase in number and length of regenerated neurites when compared to the NC. This effect was reversed by daily medium change. A guided neurite growth to the NT3 source was not detected.

Outlook:

The release of NT3 over 14 days via mini-osmotic pump under simulated in vivo conditions supported a neurite regeneration in the NOC. Further experiments have to show if an adjustment of the NOC design or the NT3-concentration can induce a guided neurite growth towards the pump.

Publication History

Article published online:
24 May 2022