The cochlea is a common site for clinical pathology in our modern society. Tens of thousands of Americans are affected every year by inner ear diseases such as Mnire's, sudden sensorineural hearing loss (SSNHL), and tinnitus. If not treated properly and in a timely manner, these illnesses can have a debilitating, chronic effect on one's hearing or balance, and significantly decrease their quality of life. Unfortunately the cochlea is surrounded by one of the hardest bones in the body, and is quite difficult to reach anatomically. Some currently available treatments for these diseases are limited by their reliance on the medications to reach the inner ear via the bloodstream or through simple diffusion from the middle ear, while others necessitate making destructive holes in the cochlear bone and breaching the scala tympani. Thus, to date no method exists to provide effective, precisely dosed delivery of inner ear therapeutics without risking permanent damage to one's hearing. To circumvent this barrier, the researchers aim to create micro- perforations through the ear's natural round window membrane (RWM) to access the inner ear fluid for drug delivery. The mechanical properties of this border between the middle and inner ears will first be explored to deepen the scientific understanding of the RWM. Techniques such as nanoindentation, laser interferometry, digital microscopy, micro CT (CT), and high fidelity finit element modeling will be utilized for a complete picture of the RWM properties under both local and global pressures throughout the process of perforation. Based on the results of these studies, various arrays of both solid and hollow silicon microneedles will be designed using isotropic etching and cryogenic processes. These needles will first be tested for their propensity to buckle or bend, and needle design will be optimized for safety during RWM perforation. A series of in vitro then in vivo studies will follow, using guinea pigs as an appropriate animal model. These studies will assess the ability of temporary solid microperforations or microinjection systems through implanted hollow needles to reliably increase the permeability of the RWM. The effect of these needles on RWM histology, the ability of the RWM to heal post-perforation, and the impact of the needles on guinea pig hearing will also be assessed. Finally, the perforations will be analyzed for their ability to consistently provide precise intracochlear drug concentrations. Our animal studies will be followed by the same studies in in vitro, fresh human temporal bone samples, with the ultimate goal of creating a manual mechanical device to deliver microperforations in clinical trials. Once optimized for the specific properties of the human RWM, such a device could allow for safe, quick, effective perforations into the inner ear in the clinic. With the use of hollow needles, this device could both sample inner ear perilymph and inject mediations when necessary, opening up a new realm of inner-ear diagnostics while then providing a means of precise, personalized treatment of often previously idiopathic inner ear pathologies.

Public Health Relevance

No method currently exists to provide effective and precisely dosed delivery of therapeutics to the inner ear without risking permanent damage to the patient's hearing. We will develop arrays of microneedles (both solid and hollow) that can quickly, safely and temporarily perforate the round window membrane (RWM) separating the middle ear and the inner ear without compromising a patient's hearing. Using solid needles, precise dosages of therapeutics will be introduced into the inner ear via diffusion through the perforations in the RWM. Using hollow needles, perilymph fluid from within the inner ear can be extracted for diagnostic purposes and therapeutics can be injected directly.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Special Emphasis Panel (ZDC1)
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Miller, Roger
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Columbia University (N.Y.)
Schools of Medicine
New York
United States
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Aksit, Aykut; Arteaga, Daniel N; Arriaga, Miguel et al. (2018) In-vitro perforation of the round window membrane via direct 3-D printed microneedles. Biomed Microdevices 20:47
Watanabe, Hirobumi; Cardoso, Luis; Lalwani, Anil K et al. (2016) A dual wedge microneedle for sampling of perilymph solution via round window membrane. Biomed Microdevices 18:24
Stevens, James P; Watanabe, Hirobumi; Kysar, Jeffrey W et al. (2016) Serrated needle design facilitates precise round window membrane perforation. J Biomed Mater Res A 104:1633-7