We use confocal microscopy to directly visualize the spatial fluctuations in fluid flow through a three-dimensional porous medium. We find that the velocity magnitudes and the velocity components both along and transverse to the imposed flow direction are exponentially distributed, even with residual trapping of a second immiscible fluid. Moreover, we find pore-scale correlations in the flow that are determined by the geometry of the medium. Our results suggest that despite the considerable complexity of the pore space, fluid flow through it is not completely random.

Objectives The treatment of inner ear disorders remains challenging due to anatomic barriers intrinsic to the bony labyrinth. The purpose of this review is to highlight recent advances and strategies for overcoming these barriers and to discuss promising future avenues for investigation. Data Sources The databases used were PubMed, EMBASE, and Web of Science. Results Although some studies aimed to improve systemic delivery using nanoparticle systems, the majority enhanced local delivery using hydrogels, nanoparticles, and microneedles. Developments in direct intracochlear delivery include intracochlear injection and intracochlear implants. Conclusions In the absence of a systemic drug that targets only the inner ear, the best alternative is local delivery that harnesses a combination of new strategies to overcome anatomic barriers. The combination of microneedle technology with hydrogel and nanoparticle delivery is a promising area for future investigation. Level of Evidence NA

Hypothesis: Three-dimensional (3D)-printed microneedles can create precise holes on the scale of micrometers in the human round window membrane (HRWM). Background: An intact round window membrane is a barrier to delivery of therapeutic and diagnostic agents into the inner ear. Microperforation of the guinea pig round window membrane has been shown to overcome this barrier by enhancing diffusion 35-fold. In humans, the challenge is to design a microneedle that can precisely perforate the thicker HRWM without damage. Methods: Based on the thickness and mechanical properties of the HRWM, two microneedle designs were 3D-printed to perforate the HRWM from fresh frozen temporal bones in situ (n = 18 total perforations), simultaneously measuring force and displacement. Perforations were analyzed using confocal microscopy; microneedles were examined for deformity using scanning electron microscopy. Results: HRWM thickness was determined to be 60.1 ± 14.6 (SD) μm. Microneedles separated the collagen fibers and created slit-shaped perforations with the major axis equal to the microneedle shaft diameter. Microneedles needed to be displaced only minimally after making initial contact with the RWM to create a complete perforation, thus avoiding damage to intracochlear structures. The microneedles were durable and intact after use. Conclusion: 3D-printed microneedles can create precise perforations in the HRWM without damaging intracochlear structures. As such, they have many potential applications ranging from aspiration of cochlear fluids using a lumenized needle for diagnosis and creating portals for therapeutic delivery into the inner ear.

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.