3D Printed Cell Culture Chamber for Testing the Effect of Pump-Based Chronic Drug Delivery on Inner Ear Tissue

Area of Science:

• Biomedical Engineering
• Neuroscience
• Otolaryngology

Background:

• Sensory neural hearing loss results from cochlear hair cell damage and spiral ganglion neuron (SGN) degeneration.
• Cochlear implants (CIs) electrically stimulate SGNs, but their functionality depends on SGN health and proximity to electrodes.
• Neurotrophic factors may improve SGN survival and neurite outgrowth, optimizing the electrode-nerve interaction for better CI performance.

Purpose of the Study:

• To develop and validate an in vitro model for chronic drug delivery to SGNs.
• To investigate the potential of neurotrophic factors to enhance SGN neurite outgrowth for improved CI functionality.

Main Methods:

• Designed and 3D-printed a novel, inner ear-inspired Neurite Outgrowth Chamber (NOC).
• Incorporated a mini-osmotic pump for controlled, long-term drug delivery within the NOC.
• Validated the NOC using spiral ganglion explants treated with ciliary neurotrophic factor, neurotrophin-3, or control fluid over two weeks.

Main Results:

• The NOC successfully supported explant cultivation and observed pump-based drug delivery over 14 days.
• Neurotrophin-3 treatment significantly increased SGN neurite outgrowth compared to control and ciliary neurotrophic factor groups.
• The model demonstrated suitability for assessing the effects of chronic neurotrophic factor delivery on SGNs.

Conclusions:

• The developed Neurite Outgrowth Chamber is a viable in vitro model for studying chronic drug delivery to spiral ganglion neurons.
• Neurotrophin-3 shows promise in promoting SGN neurite outgrowth, potentially enhancing cochlear implant efficacy.
• This model could facilitate further research into neuroprotective strategies for sensory neural hearing loss.