Contrast Enhancement of Cochlea after Direct Microneedle Intracochlear Injection of Gadodiamide through the Round Window Membrane with Minimal Dosage.

Rationale And Objectives: The potential of contrast-enhanced MRI for diagnosing endolymphatic hydrops is limited by long wait times following intravenous (IV) or intratympanic (IT) delivery, high contrast dosages, and inconsistent signal intensity enhancements. This study investigates microneedle-mediated intracochlear (IC) gadodiamide injection for consistent and efficient contrast delivery with minimal contrast dosage.

Materials And Methods: A 100 µm diameter microneedle with 35 µm lumen was used to inject 1 µL of diluted gadodiamide (17.

Microneedle-Mediated Delivery of siRNA via Liposomal-Based Transfection for Inner Ear Gene Therapy.

Hypothesis: Microneedle-mediated intracochlear injection of siRNA-Lipofectamine through the round window membrane (RWM) can be used to transfect cells within the cochlea.

Background: Our laboratory has developed 100-μm diameter hollow microneedles for intracochlear injection through the guinea pig RWM. In this study, we test the feasibility of microneedle-mediated injection of siRNA and Lipofectamine, a commonly used reagent with known cellular toxicity, through the RWM for cochlear transfection.

Exploring Inner Ear and Brain Connectivity through Perilymph Sampling for Early Detection of Neurological Diseases: A Provocative Proposal.

Recent evidence shows that it is possible to identify the elements responsible for sensorineural hearing loss, such as pro-inflammatory cytokines and macrophages, by performing perilymph sampling. However, current studies have only focused on the diagnosis of such as otologic conditions. Hearing loss is a feature of certain neuroinflammatory disorders such as multiple sclerosis, and sensorineural hearing loss (SNHL) is widely detected in Alzheimer's disease.

Physiologic Effects of Microneedle-Mediated Intracochlear Dexamethasone Injection in the Guinea Pig.

Objectives: Oral or intratympanic corticosteroids are commonly used to treat sudden sensorineural hearing loss (SSHL), tinnitus, and Meniere disease. Direct intracochlear delivery has been proposed to overcome the variability in bioavailability and efficacy of systemic or middle ear delivery. In this study, we aim to characterize the physiologic consequences of microneedle-mediated direct intracochlear injection of dexamethasone through the round window membrane (RWM).

Microneedles Facilitate Small-Volume Intracochlear Delivery Without Physiologic Injury in Guinea Pigs.

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: We have developed polymeric microneedles that allow for in vivo perforation of the guinea pig RWM and aspiration of perilymph for diagnostic analysis, with full reconstitution of the RWM within 48 to 72 hours. In this study, we investigate the ability of microneedles to deliver precise volumes of therapeutics into the cochlea and assess the subsequent consequences on hearing.

Anatomic, physiologic, and proteomic consequences of repeated microneedle-mediated perforations of the round window membrane.

Background: We have developed 3D-printed microneedle technology for diagnostic aspiration of perilymph and intracochlear delivery of therapeutic agents. Single microneedle-mediated round window membrane (RWM) perforation does not cause hearing loss, heals within 48-72 h, and yields sufficient perilymph for proteomic analysis. In this study, we investigate the anatomic, physiologic, and proteomic consequences of repeated microneedle-mediated perforations of the same RWM at different timepoints.

In Vitro Proof of Concept of a First-Generation Growth-Accommodating Heart Valved Conduit for Pediatric Use.

Currently available heart valve prostheses have no growth potential, requiring children with heart valve diseases to endure multiple valve replacement surgeries with compounding risks. This study demonstrates the in vitro proof of concept of a biostable polymeric trileaflet valved conduit designed for surgical implantation and subsequent expansion via transcatheter balloon dilation to accommodate the growth of pediatric patients and delay or avoid repeated open-heart surgeries. The valved conduit is formed via dip molding using a polydimethylsiloxane-based polyurethane, a biocompatible material shown here to be capable of permanent stretching under mechanical loading.

Engineering edgeless human skin with enhanced biomechanical properties.

Despite the advancements in skin bioengineering, 3D skin constructs are still produced as flat tissues with open edges, disregarding the fully enclosed geometry of human skin. Therefore, they do not effectively cover anatomically complex body sites, e.g.

Pyrolyzed Ultrasharp Glassy Carbon Microneedles.

Polymeric microneedles fabricated via two-photon polymerization (2PP) lithography enable safe medical access to the inner ear. Herein, the material class for 2PP-lithography-based microneedles is expanded by pyrolyzing 2PP-fabricated polymeric microneedles, resulting in glassy carbon microneedles. During pyrolysis the microneedles shrink up to 81% while maintaining their complex shape when the exposed surface-area-to-volume ratio (SVR) is 0.

Inner Ear Diagnostics and Drug Delivery via Microneedles.

Objectives: Precision medicine for inner ear disorders has seen significant advances in recent years. However, unreliable access to the inner ear has impeded diagnostics and therapeutic delivery. The purpose of this review is to describe the development, production, and utility of novel microneedles for intracochlear access.

A biomimetic multilayered polymeric material designed for heart valve repair and replacement.

Materials currently used to repair or replace a heart valve are not durable. Their limited durability related to structural degeneration or thrombus formation is attributed to their inadequate mechanical properties and biocompatibility profiles. Our hypothesis is that a biostable material that mimics the structure, mechanical and biological properties of native tissue will improve the durability of these leaflets substitutes and in fine improve the patient outcome.

Membrane curvature and connective fiber alignment in guinea pig round window membrane.

The round window membrane (RWM) covers an opening between the perilymph fluid-filled inner ear space and the air-filled middle ear space. As the only non-osseous barrier between these two spaces, the RWM is an ideal candidate for aspiration of perilymph for diagnostics purposes and delivery of medication for treatment of inner ear disorders. Routine access across the RWM requires the development of new surgical tools whose design can only be optimized with a thorough understanding of the RWM's structure and properties.

Design optimization of a cardiovascular stent with application to a balloon expandable prosthetic heart valve.

A cardiovascular stent design optimization method is proposed with application to a pediatric balloon-expandable prosthetic heart valve. The prosthetic valved conduit may be expanded to a larger permanent diameter via subsequent transcatheter balloon dilation procedures. While multiple expandable prosthetic heart valves are currently at different stages of development, this work is focused on one particular design in which a stent is situated inside of an expandable polymeric valved conduit.

Impact of Systemic versus Intratympanic Dexamethasone Administration on the Perilymph Proteome.

Glucocorticoids are the first-line treatment for sensorineural hearing loss, but little is known about the mechanism of their protective effect or the impact of route of administration. The recent development of hollow microneedles enables safe and reliable sampling of perilymph for proteomic analysis. Using these microneedles, we investigate the effect of intratympanic (IT) versus intraperitoneal (IP) dexamethasone administration on guinea pig perilymph proteome.

A Novel 3D-Printed Head Holder for Guinea Pig Ear Surgery.

Background: Otologic surgery in guinea pig requires head immobilization for microscopic manipulation. Existing commercially available stereotaxic frames are expensive and impede access to the ear as they rely on ear bars or mouthpieces to secure the head.

Method: Prototype head holders were designed using the Solidworks 2019 software and 3D-printed using Formlabs Form 2 Printers with photopolymer resin.

Simulation assisted design for microneedle manufacturing: Computational modeling of two-photon templated electrodeposition.

Fully metallic micrometer-scale 3D architectures can be fabricated via a hybrid additive methodology combining multi-photon lithography with electrochemical deposition of metals. The methodology - referred to as two-photon templated electrodeposition (2PTE) - has significant design freedom that enables the creation of complicated, traditionally difficult-to-make, high aspect ratio metallic structures such as microneedles. These complicated geometries, combined with their fully metallic nature, can enable precision surgical applications such as inner ear drug delivery or fluid sampling.

Inner Ear Gene Delivery: Vectors and Routes.

Objectives: Current treatments for hearing loss offer some functional improvements in hearing, but do not restore normal hearing. The aim of this review is to highlight recent advances in viral and non-viral vectors for gene therapy and to discuss approaches for overcoming barriers inherent to inner ear delivery of gene products.

Data Sources: The databases used were Medline, EMBASE, Web of Science, and Google Scholar.

Novel 3D-printed hollow microneedles facilitate safe, reliable, and informative sampling of perilymph from guinea pigs.

Background: Inner ear diagnostics is limited by the inability to atraumatically obtain samples of inner ear fluid. The round window membrane (RWM) is an attractive portal for accessing perilymph samples as it has been shown to heal within one week after the introduction of microperforations. A 1 µL volume of perilymph is adequate for proteome analysis, yet the total volume of perilymph within the scala tympani of the guinea pig is limited to less than 5 µL.

Facile and quantitative estimation of strain in nanobubbles with arbitrary symmetry in 2D semiconductors verified using hyperspectral nano-optical imaging.

When layers of van der Waals materials are deposited via exfoliation or viscoelastic stamping, nanobubbles are sometimes created from aggregated trapped fluids. Though they can be considered a nuisance, nanobubbles have attracted scientific interest in their own right owing to their ability to generate large in-plane strain gradients that lead to rich optoelectronic phenomena, especially in the semiconducting transition metal dichalcogenides. Determination of the strain within the nanobubbles, which is crucial to understanding these effects, can be approximated using elasticity theory.

Imaging strain-localized excitons in nanoscale bubbles of monolayer WSe at room temperature.

In monolayer transition-metal dichalcogenides, localized strain can be used to design nanoarrays of single photon sources. Despite strong empirical correlation, the nanoscale interplay between excitons and local crystalline structure that gives rise to these quantum emitters is poorly understood. Here, we combine room-temperature nano-optical imaging and spectroscopic analysis of excitons in nanobubbles of monolayer WSe with atomistic models to study how strain induces nanoscale confinement potentials and localized exciton states.

Drug delivery device for the inner ear: ultra-sharp fully metallic microneedles.

Drug delivery into the inner ear is a significant challenge due to its inaccessibility as a fluid-filled cavity within the temporal bone of the skull. The round window membrane (RWM) is the only delivery portal from the middle ear to the inner ear that does not require perforation of bone. Recent advances in microneedle fabrication enable the RWM to be perforated safely with polymeric microneedles as a means to enhance the rate of drug delivery from the middle ear to the inner ear.

Unchanged cerebrovascular CO reactivity and hypercapnic ventilatory response during strict head-down tilt bed rest in a mild hypercapnic environment.

Key Points: Carbon dioxide levels are mildly elevated on the International Space Station and it is unknown whether this chronic exposure causes physiological changes to astronauts. We combined ∼4 mmHg ambient with the strict head-down tilt bed rest model of spaceflight and this led to the development of optic disc oedema in one-half of the subjects. We demonstrate no change in arterialized , cerebrovascular reactivity to CO or the hypercapnic ventilatory response.

Inner ear delivery: Challenges and opportunities.

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.

Anatomical and Functional Consequences of Microneedle Perforation of Round Window Membrane.

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.

3D-Printed Microneedles Create Precise Perforations in Human Round Window Membrane in Situ.

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.