Medical Student Columbia University Vagelos College of Physicians & Surgeons New York, New York
Hypothesis: Microneedle-mediated intracochlear injection through the round window membrane (RWM) will facilitate intracochlear delivery, not affect hearing, and allow for full reconstitution of the RWM within 48 hours.
Background: Previously, hollow microneedles developed in our laboratory were shown to be capable of perforating the RWM and aspirating perilymph for diagnostic proteomic analysis without cochlear damage. There is similar need for tools to facilitate atraumatic intracochlear delivery to implement inner ear therapies. In this study, we assess the feasibility and consequences of direct intracochlear injection of material via hollow microneedles.
Methods: Two-photon polymerization lithography was used to 3D-print 100μm-diameter hollow microneedles. Tympanic bullae of guinea pigs were extracted, RWMs were perforated ex vivo, and 1μL of 10mM rhodamine was injected into the cochlea over 1 minute. Similarly, 1μL of artificial perilymph was injected over 1 minute in vivo in guinea pigs. Distortion product otoacoustic emissions (DPOAE) and compound action potential (CAP) were recorded prior to in vivo perforation and 48 hours following injection. After euthanasia, the RWM was harvested for confocal microscopy.
Results: Ex vivo assessment of the cochlea under light microscopy revealed distribution of rhodamine throughout the basal turn of the cochlea immediately following injection, followed by slow diffusion through the middle and apical turns. Following in vivo injection, there were no significant changes in DPOAE and CAP. Confocal microscopy demonstrated full reconstitution of the RWM without inflammation or residual perforation.
Conclusions: Hollow microneedles are safe and effective for intracochlear injection of agents, thus making inner eartherapy possible without concomitant damage or hearing loss.
*Professional Practice Gap & Educational Need: Currently, no clinical technology exists for diagnostic aspiration of perilymph and direct intracochlear injection of therapeutics. Our 3D-printed hollow microneedles have the potential to fill this practice gap. By demonstrating the safety and efficacy of direct intracochlear injection via hollow microneedles, we create new avenues for inner ear intervention, including inner ear gene therapy.
*Learning Objective: To understand the current landscape of direct intracochlear delivery. To understand the contribution that our technology makes to the field.
*Desired Result: Increased interest and investment in 3D-printed hollow microneedles for intracochlear delivery of therapeutics.
*Level of Evidence: n/a
*Indicate IRB or IACUC: Columbia University Irving Medical Center – IACUC No. AABA5450 (approved 3/8/2021)