Anatomical and Functional Consequences of Microneedle Perforation of Round Window Membrane

Abstract

Hypothesis: Microneedles can create microperforations in the round window membrane (RWM) without causing anatomic or physiologic damage.Background: Reliable delivery of agents into the inner ear for therapeutic and diagnostic purposes remains a challenge. Our novel approach employs microneedles to facilitate intracochlear access via the RWM. This study investigates the anatomical and functional consequences of microneedle perforations in guinea pig RWMs in vivo.Methods: Single 3D-printed, 100 μm diameter microneedles were used to perforate the guinea pig RWM via the postauricular sulcus. Hearing was assessed both before and after microneedle perforation using compound action potential and distortion product otoacoustic emissions. Confocal microscopy was used ex vivo to examine harvested RWMs, measuring the size, shape, and location of perforations and documenting healing at 0 hours (n = 7), 24 hours (n = 6), 48 hours (n = 6), and 1 week (n = 6).Results: Microneedles create precise and accurate perforations measuring 93.1 ± 29.0 μm by 34.5 ± 16.8 μm and produce a high frequency threshold shift that disappears after 24 hours. Examination of perforations over time demonstrates healing progression over 24-48 hours and complete perforation closure by one week. Conclusion:Microneedles can create a temporary microperforation in the RWM without causing significant anatomic or physiologic dysfunction. Microneedles have the potential to mediate safe and effective intracochlear access for diagnosis and treatment of inner ear disease.

Inner ear delivery: Challenges and opportunities

“…41,45 In the guinea pig, these perforations are not associated with any notable lasting effects on hearing, and the perforations also heal within a week after perforation. 45 Microneedles can also create precise perforations in the human RWM. 39 One of the challenges of microneedle use on the RWM is ensuring that the needle is inserted far enough to create a perforation but not so far as to cause damage to structures behind the RWM.…”

“…40,41 To date, several needle designs have been fabricated with an assortment of unique characteristics. 39,[41][42][43][44][45] Microneedles fabricated using two-photon polymerization (2PP) are able to perforate guinea pig RWM reliably. 41,45 In the guinea pig, these perforations are not associated with any notable lasting effects on hearing, and the perforations also heal within a week after perforation.…”

“…Microneedles are designed with the microanatomic and mechanical properties of the RWM in mind, to create controlled and precise perforations in the membrane with minimal trauma (Figure ) . To date, several needle designs have been fabricated with an assortment of unique characteristics . Microneedles fabricated using two‐photon polymerization (2PP) are able to perforate guinea pig RWM reliably .…”

“…Microneedles fabricated using two‐photon polymerization (2PP) are able to perforate guinea pig RWM reliably . In the guinea pig, these perforations are not associated with any notable lasting effects on hearing, and the perforations also heal within a week after perforation . Microneedles can also create precise perforations in the human RWM .…”

Impact of Systemic versus Intratympanic Dexamethasone Administration on the Perilymph Proteome

“…Our laboratory has developed novel microneedle technology for inner ear diagnosis and therapy based on the mechanical properties of the round window membrane (RWM). − An additive manufacturing technique, two-photon polymerization lithography (2PP), was used to direct-write the microneedles via three-dimensional (3D) printing. Solid microneedles fabricated using this technique introduced microperforations in vivo that healed within 1 week without functional consequences. , Hollow microneedles (Figure ) were then successfully used for atraumatic aspiration of perilymph across the RWM at a quality and volume adequate for proteomic analysis without causing lasting anatomic and functional dysfunction . These hollow microneedles could be used to sample perilymph of untreated guinea pigs and glucocorticoid-treated guinea pigs for comparison using liquid chromatography/mass spectrometry.…”