(A845) Novel 3D-Printed Microneedles Enable Controlled Perforations in Mouse Round Window Membranes: Insights for Human Applications

Introduction: Inner ear therapeutics is a growing field of study with promising pharmacologic and technologic advances, particularly gene therapy. Delivery to the inner ear, however, is an age-old problem given the cochlea’s bony housing. 3D-printed microneedle technology has enabled access to the cochlea via the round window membrane (RWM) with precision and versatility, providing an avenue for both diagnosis and treatment of inner ear diseases. We demonstrate adaptability of this technology for use in mice, which are model organisms for testing gene therapy that may one day be used in humans.

Methods: 3D-printed microneedles adapted from designs for guinea pig and human cadaveric RWM were used to perforate mouse RWM in vitro, accommodating for less than half the membrane area and deeper RWM position within the bony niche. Perforation forces and displacement were measured using a custom microindentation setup and perforation size and shape were examined using confocal microscopy. Microneedles were examined with optical microscopy for post-perforation integrity.

Results: Perforations reached a peak force of 1.4 ± 0.2 mN (n=5). Perforation sizes corresponded reliably to 33 µm microneedle diameter and were predictably lens-shaped and aligned with RWM fibers, as observed in prior studies: major axis 33.4 ± 1.1 µm, minor axis 10.8 ± 0.5 µm (n=3). On examination of the microneedles after perforation, there was minor blunting of tips but no major deformation.

Conclusions: Perforation forces and sizes as well as microneedle integrity reported here demonstrate efficacy of a design based on constraints of mouse RWM anatomy. The versatility of the technology illustrated by this study contributes to a microneedle engineering framework that will set the stage for advancing human inner ear access.