Biomimetic Artificial Basilar Membranes for Next-Generation Cochlear Implants.

Patients with sensorineural hearing loss can recover their hearing using a cochlear implant (CI). However, there is a need to develop next-generation CIs to overcome the limitations of conventional CIs caused by extracorporeal devices. Recently, artificial basilar membranes (ABMs) are actively studied for next-generation CIs. The ABM is an acoustic transducer that mimics the mechanical frequency selectivity of the BM and acoustic-to-electrical energy conversion of hair cells. This paper presents recent progress in biomimetic ABMs. First, the characteristics of frequency selectivity of the ABMs by the trapezoidal membrane and beam array are addressed. Second, to reflect the latest research of energy conversion technologies, ABMs using various piezoelectric materials and triboelectric-based ABMs are discussed. Third, in vivo evaluations of the ABMs in animal models are discussed according to the target position for implantation. Finally, future perspectives of ABM studies for the development of practical hearing devices are discussed.

A cochlear-bone wave can yield a hearing sensation as well as otoacoustic emission.

A hearing sensation arises when the elastic basilar membrane inside the cochlea vibrates. The basilar membrane is typically set into motion through airborne sound that displaces the middle ear and induces a pressure difference across the membrane. A second, alternative pathway exists, however: stimulation of the cochlear bone vibrates the basilar membrane as well. This pathway, referred to as bone conduction, is increasingly used in headphones that bypass the ear canal and the middle ear. Furthermore, otoacoustic emissions, sounds generated inside the cochlea and emitted therefrom, may not involve the usual wave on the basilar membrane, suggesting that additional cochlear structures are involved in their propagation. Here we describe a novel propagation mode within the cochlea that emerges through deformation of the cochlear bone. Through a mathematical and computational approach we demonstrate that this propagation mode can explain bone conduction as well as numerous properties of otoacoustic emissions.

Measurement of cochlear power gain in the sensitive gerbil ear.

The extraordinary sensitivity of the mammalian ear is commonly attributed to the cochlear amplifier, a cellular process thought to locally boost responses of the cochlear partition to soft sounds. However, cochlear power gain has not been measured directly. Here we use a scanning laser interferometer to determine the volume displacement and volume velocity of the cochlear partition by measuring its transverse vibration along and across the partition. We show the transverse displacement at the peak-response location can be >1,000 times greater than the displacement of the stapes, whereas the volume displacement of an area centred at this location is approximately tenfold greater than that of the stapes. Using the volume velocity and cochlear-fluid impedance, we discover that power at the peak-response area is >100-fold greater than that at the stapes. These results demonstrate experimentally that the cochlea amplifies soft sounds, offering insight into the mechanism responsible for the cochlear sensitivity.

Localization of fatty acid binding proteins (FABPs) in the cochlea of mice.

Various fatty acids (FAs) are involved in many different functions in the organism as a source of energy, as essential ingredients of membranous lipids as well as intracellular signaling molecules. Intracellular fatty acid binding proteins (FABPs) comprise a family of soluble lipid binding proteins with low molecular masses and which can make long chain FAs soluble to allow intracellular translocation in the aqueous cytosol. To clarify the possible involvement of FAs and FABPs in hearing function, the present study investigated the localization of FABPs in the cochlea of adult mice using immunohistochemical procedures. Among various FABP species, H (heart-type)-FABP was localized in inner and outer pillar cells and outer phalangeal cells, while B (brain-type)-FABP was localized in border cells and cells of Hensen, and fibrocytes in the spiral limbus and spiral prominence. In the spiral ganglion, moderate to low H-FABP immunoreactivity was observed in almost all neurons, while B-FABP immunoreactivity was found in satellite cells. The discrete localization of the two FABPs in different non-receptor cells in the Organ of Corti suggests that the FABP species and/or their ligands, FAs, play important roles in the regulation of the hearing function.

Cholinergic innervation of the chick basilar papilla.

Antibodies directed against choline acetyltransferase (ChAT), the synthesizing enzyme for acetylcholine (ACh) and a specific marker of cholinergic neurons, were used to label axons and nerve terminals of efferent fibers that innervate the chick basilar papilla (BP). Two morphologically distinct populations of cholinergic fibers were labeled and classified according to the region of the BP they innervated. The inferior efferent system was composed of thick fibers that coursed radially across the basilar membrane in small fascicles, gave off small branches that innervated short hair cells with large cup-like endings, and continued past the inferior edge of the BP to ramify extensively in the hyaline cell area. The superior efferent system was made up of a group of thin fibers that remained in the superior half of the epithelium and innervated tall hair cells with bouton endings. Both inferior and superior efferent fibers richly innervated the basal two thirds of the BP. However, the apical quarter of the chick BP was virtually devoid of efferent innervation except for a few fibers that gave off bouton endings around the peripheral edges. The distribution of ChAT-positive efferent endings appeared very similar to the population of efferent endings that labeled with synapsin antisera. Double labeling with ChAT and synapsin antibodies showed that the two markers colocalized in all nerve terminals that were identified in BP whole-mounts and frozen sections. These results strongly suggest that all of the efferent fibers that innervate the chick BP are cholinergic.

An analysis of actin isoforms expressed in hair-cell enriched fractions of the chick basilar papilla by the polymerase chain reaction technique.

Actin mRNA was characterised in hair-cell enriched fractions of the chick basilar papilla, by means of the reverse-transcription polymerase chain reaction technique. Primers were directed against the 3' untranslated portions of the actin mRNAs. Evidence for beta-cytoplasmic and gamma-cytoplasmic actin mRNA was found; no evidence was found for alpha-skeletal, alpha-cardiac or type 5 cytoplasmic actin mRNAs. Since beta-actin is known to form bundles of filaments whereas gamma-actin does not, this suggests that the hair-cell stereocilia are composed of beta-actin.

Fibronectin-like immunoreactivity of the basilar membrane of young and aged rats.

Dysfunction of cochlear mechanics has been hypothesized to be a source of age-related hearing loss and the basilar membrane mass and stiffness contribute to normal cochlear mechanics. Fibronectin, a large, extracellular matrix protein and a major component of the basilar membrane, may contribute to both the mass and stiffness of the membrane. Mesothelial cells underlying the basilar membrane may produce the fibronectin and also contribute to the mass of the membrane. Changes in either the fibronectin or the mesothelial cells might, therefore, have an effect on cochlear mechanics. In order to assess basilar membrane changes in aged animals, young adult (2-4 months) and aged (24-26 months) Sprague-Dawley rats were evaluated for the presence of fibronectin-like protein and mesothelial cells. The basilar membrane in the young animals had strong fibronectin-like immunoreactivity throughout its length. The old animals, on the other hand, showed normal fibronectin immunoreactivity in the basilar membrane of the basal turn, but little or no reactivity in the apical cochlear turn. The number of mesothelial cells was reduced throughout the length of the membrane in aged animals, with the greatest loss in the basal turn (60% fewer cells). These two degenerative changes, which appear to be independent of each other, may contribute to the observed threshold shifts in aged cochleas.

Cytokeratin expression in the epithelia of the adult human cochlea.

Epithelia can be characterized by the specific expression pattern of their cytokeratin components. Therefore, we investigated the immunohistochemical expression of different cytokeratin subunits in frozen sections of chemically fixed, non-decalcified, adult human cochleas. The organ of Corti and the marginal cells of the stria vascularis showed reactivity for cytokeratin subunits 8, 18 and 19, whereas the other cochlear epithelia in addition expressed cytokeratin 7. The expression of cytokeratins 7, 8, 18 and 19 by the epithelia of the adult human cochlea is typical of "simple" epithelia. The deviant cytokeratin pattern of the organ of Corti and marginal cells of the stria vascularis may well reflect their differences in functional state and/or differentiation as compared to the other cochlear epithelia.