PURPOSE:Cartilage is widely used for tympanic membrane (TM) reconstruction, but the impact of graft position relative to the bony ear canal on middle ear mechanics remains unclear. This study examined how cartilage placement affects the middle ear transfer function (METF) and TM vibration. METHODS:Single‑point Laser Doppler Vibrometry (LDV) was performed on five fresh frozen human temporal bones before and after creating a 2.5 mm perforation in the posterior inferior TM quadrant and after reconstruction with a round-shaped cartilage graft of 4 mm diameter and 0.5 mm thickness placed either on (on‑bony) or separated from (off‑bony) the bony ear canal. TM motion was further assessed using a scanning LDV in a technical membrane model. A validated finite element (FE) model of the middle ear was used to replicate temporal bone measurements and the effect of an experimentally opened versus closed tympanic cavity, representing the in-vivo condition in patients, was evaluated by FE modelling. RESULTS:After TM perforation, the METF significantly decreased between 562 - 2094 Hz, and 2951 - 3194 Hz, while showing increased measurement variability below 500 Hz. When performing reconstruction with either the on-bony or the off-bony technique, the METFs partially recover, but show a significant difference in METF compared to the intact TM in the frequency range of 146 - 195, 200 - 217, 739 - 933 Hz (on-bony) and 146 - 295, 718 - 930, 722 - 930 and 1332 - 1719 Hz (off-bony). No significant difference in METF between the on-bony and off-bony reconstruction were found (p > 0.05). Scanning LDV analysis of a technical membrane model showed similar membrane peak velocities between the two graft positions, although the off‑bony configuration shifted the best frequency to lower values. FE simulations of the middle ear confirmed the findings of the temporal bone measurements. Additionally, the model work showed that middle ear transmission with an experimentally opened tympanic cavity differed by <2 dB after on- or off-bony reconstruction compared to a closed tympanic cavity. This was different for the perforated TM: While the transmission loss was nearly constant with an experimentally opened tympanic cavity, a closed tympanic cavity produced frequency‑dependent transmission loss exceeding 40 dB. CONCLUSION:In this temporal bone study, placing the cartilage on the bony ear canal wall did not have an impact on the METF. FE modeling supported the temporal bone findings and suggested that similar behavior could be expected in vivo with a closed tympanic cavity. However, the FE-model suggests that perforation‑induced losses were substantially underestimated in the temporal bone measurements with an experimentally opened tympanic cavity. Positioning of the cartilage graft on the bony ear canal can be advantageous in patients with chronic middle-ear disease to reduce the risk of medialization and formation of retraction pockets without compromising the patients hearing outcome.

The sensation of mechanical stimuli is initiated by elastic gating springs that pull open mechanosensory transduction channels. Searches for gating springs have focused on force-conveying protein tethers such as the amino-terminal ankyrin tether of the Drosophila mechanosensory transduction channel NOMPC. Here, by combining protein domain duplications with mechanical measurements, electrophysiology, molecular dynamics simulations and modeling, we identify the NOMPC gating-spring as the short linker between the ankyrin tether and the channel gate. This linker acts as a Hookean hinge that is ten times more elastic than the tether, with the linker hinge dictating channel gating and the intrinsic stiffness of the gating spring. Our study shows how mechanosensation is initiated molecularly; disentangles gating springs and tethers, and respective paradigms of channel gating; and puts forward gating springs as core ion channel constituents that enable efficient gating by diverse stimuli and in a wide variety of channels. Hehlert et al. report that the gating spring that pulls open mechanosensitive NOMPC channels is not their helical ankyrin tether, but instead an elastic hinge that suspends that tether on the channel gate.

Einleitung Die Rekontruktion der Gehörknöchelchenkette erfolgt überwiegend durch starre Implantate. Neue Mittelohrprothesen versuchen die physiologischen Mikrobewegungen der Gehörknöchelchenkette zu imitieren und Protrusionen zu vermeiden

Objective Middle ear surgery involves reconstruction of the ossicular chain, predominately using rigid implants. New middle ear prostheses strive to mimic the physiologic micromovements of the ossicular chain and prevent dislocation, protrusion, and preloading of the annular ligament due to pressure fluctuations. Methods Thirty‐five patients were included in a monocentric, prospective observational study. Patients received tympanoplasty with ossicular reconstruction using the mCLIP ARC partial prosthesis. This titanium prosthesis is equipped with a clip mechanism for coupling at the stapes and a ball joint connecting headplate and shaft. At short‐term (ST) and mid‐term (MT) follow‐up, pure‐tone audiometry was performed and the pure tone average of 0.5, 1, 2, and 3 kHz (PTA4) was calculated. The audiological outcome was compared with retrospective data of the Dresden titanium clip prosthesis. Results The new prosthesis shows favorable clinical results. Pure‐tone audiometry showed satisfactory results in ST and MT follow‐up, with the PTA4 air‐bone gap (ABG) decreasing from 24.5 (±11) dB to 17.4 (±7.9) dB at the ST follow‐up at 27 days to 15.6 (±10.3) dB at MT follow‐up at 196 days ( n = 32). A PTA4‐ABG value of less than 20 dB was achieved by 63% of patients at ST follow‐up and by 77% at MT follow‐up. There was no significant difference in PTA4 ABG compared to the Dresden titanium clip prosthesis during ST follow‐up ( p = 0.18). Conclusion The mCLIP ARC partial prosthesis, a new middle ear prosthesis with a balanced ball joint, shows promising audiological results and is a safe and effective choice for patients with chronic ear disease. Level of Evidence 3 Laryngoscope , 134:3323–3328, 2024

Background In mammals, a specialized auditory end organ, the Organ of Corti, is responsible for hearing. It comprises supporting cells and secondary sensory cells (inner IHC; and outer hair cells OHC). IHCs and OHCs employ mechano-electrical transduction (MET) to translate sound in electrical signals. Their sensory organelle, the hair bundle, is comprised of three rows of stereocilia, that are arranged in a staircase pattern. Deflections towards the tallest row activate MET channels. While non-auditory MET channels (such as TRAK1) can be activated or modulated by changes to their lipid environment, these interactions for mammalian auditory MET channel remain uninvestigated. Additionally, some lipid metabolism diseases lead to hearing loss/impairment, as does treatment with aminoglycosides.

Background Hearing in Drosophila requires the NOMPC (TRPN1) channel. NOMPC is a mechano-electrical transduction (MET) channel whose amino-terminal ankyrin repeat (AR) domain consists of 29 ARs, that assemble into a helical structure, tether the channel intracellularly to microtubules, and are essential for channel mechanosensitivity. Based on these data, the AR domain was implicated as the “gating spring”, an elastic element relaying forces to the channel gate.

Most mechanically gated channels are sensitive to force translated through the membrane. The lipid bilayer can modulate channel function directly through lipid/protein interactions or indirectly based on membrane mechanical properties. Cholesterol is an important component of the membrane and a major modulator of membrane mechanical properties. While other ion channels and mechanically gated channels can be activated or modulated by changes to the membrane cholesterol, the functional role of membrane cholesterol in regulation of mammalian cochlear mechanotransduction (MET) channels has not been closely investigated. Using whole-cell patch clamping and live-cell fluorescence lifetime imaging (FLIM) of a viscosity-sensitive molecular rotor BODIPY 1c for the first time in the inner ear, we examined the role of membrane cholesterol in modulating the MET response properties of rat cochlear hair cells. Molecular rotors are fluorophores for which the fluorescence lifetime (the average time a fluorophore remains in the excited state) increase with increasing viscosity of their immediate environment. We confirmed extraction of cholesterol, using methyl β cyclodextrin (MβCD), with reduced filipin staining in both inner and outer hair bundles. MβCD results in reversible reduction in fluorescence lifetime in hair bundles, suggesting initial reduction followed by gradual recovery in the stereocilia membrane viscosity. MβCD reversibly increases the channel resting open probability, suggesting that cholesterol depletion increases force transfer to the MET channel. Together this data suggests that the cell membrane is part of the force relay machinery to the MET channel and could possibly interact directly with components of the MET machinery. Further studies are needed to generate causal link between MET channel gating and membrane mechanics.

Background Sensitive hearing in Drosophila requires the NOMPC (TRPN1) channel. NOMPC is a bona fide mechano-electrical transduction (MET) channel whose amino-terminal ankyrin repeat (AR) domain consists of 29 ARs. These 29 ARs assemble into a helical structure, tether the channel intracellularly to microtubules, and are essential for mechano-gating. Because of these findings it was hypothesized that the AR domain might function as the “gating spring”, an elastic element relaying forces to the channel gate. We report now that the NOMPC AR domain is not the gating spring of NOMPC and investigate other elements of the channel for their mechanical properties.

In passive middle ear prosthetics, rigid implants have proven successful in reconstructing the ossicular chain. However, these cannot fully replicate the physiology of the ossicular chain. Pressure fluctuations cause high loads in rigid passive prostheses, which can lead to dislocation, extrusion and unsatisfactory hearing results.

Injury or inflammation of the middle ear often results in the persistent tympanic membrane (TM) perforations, leading to conductive hearing loss (HL). However, in some cases the magnitude of HL exceeds that attributable by the TM perforation alone. The aim of the study is to better understand the effects of location and size of TM perforations on the sound transmission properties of the middle ear. The middle ear transfer functions (METF) of six human temporal bones (TB) were compared before and after perforating the TM at different locations (anterior or posterior lower quadrant) and to different degrees (1 mm, ¼ of the TM, ½ of the TM, and full ablation). The sound-induced velocity of the stapes footplate was measured using single-point laser-Doppler-vibrometry (LDV). The METF were correlated with a Finite Element (FE) model of the middle ear, in which similar alterations were simulated. The measured and calculated METF showed frequency and perforation size dependent losses at all perforation locations. Starting at low frequencies, the loss expanded to higher frequencies with increased perforation size. In direct comparison, posterior TM perforations affected the transmission properties to a larger degree than anterior perforations. The asymmetry of the TM causes the malleus-incus complex to rotate and results in larger deflections in the posterior TM quadrants than in the anterior TM quadrants. Simulations in the FE model with a sealed cavity show that small perforations lead to a decrease in TM rigidity and thus to an increase in oscillation amplitude of the TM mainly above 1 kHz. Size and location of TM perforations have a characteristic influence on the METF. The correlation of the experimental LDV measurements with an FE model contributes to a better understanding of the pathologic mechanisms of middle-ear diseases. If small perforations with significant HL are observed in daily clinical practice, additional middle ear pathologies should be considered. Further investigations on the loss of TM pretension due to perforations may be informative.

In der passiven Mittelohrprothetik haben sich rigide Implantate bei der Rekonstruktion der Gehörknöchelchenkette bewährt. Diese können jedoch die Physiologie der Gehörknöchelchenkette nicht vollständig nachbilden. Druckschwankungen verursachen bei starren passiven Prothesen hohe Belastungen, die zu Dislokation, Extrusion und unbefriedigenden Hörresultaten führen können.

OBJECTIVE:In passive middle ear prosthetics, rigid implants have proven successful in reconstructing the ossicular chain. However, these cannot fully replicate the physiology of the ossicular chain. Pressure fluctuations cause high stresses in rigid passive prostheses, which can result in dislocation, protrusion, and pre-tension in the annular ligament resulting in unsatisfactory hearing results.METHODS:In collaboration with MED-EL, we developed a new passive middle ear prosthesis that features a balanced, centered ball joint between the headplate and shaft of the prosthesis. We compared the sound transmission properties of this new prosthesis with those of a standard rigid prosthesis. Using Laser-Doppler-Vibrometry, we measured the sound-induced velocity of the stapes footplate relative to a given acoustic stimulus.RESULTS:The new prosthesis showed equivalent sound transmission characteristics compared to the rigid prosthesis, whereas retaining the ability to compensate for pressure fluctuations due to its ball joint. This ensures good transmission properties even during displacements of the tympanic membrane.CONCLUSION:This development is a further step toward a physiological reconstruction of the ossicular chain.LEVEL OF EVIDENCE:NA Laryngoscope, 133:1717-1721, 2023.

Das empfindliche Hören in der Taufliege (Drosophila melanogaster) benötigt den Ionenkanal NOMPC (TRPN1) [1]. NOMPC ist ein bona-fide mechanolelektrischer Transduktionskanal (MET-Kanal), der eine Domäne von 29 Ankyrinrepeats (ARs) besitzt. Diese 29 ARs formen eine Helix [2], verbinden den Kanal intrazellulär mit Mikrotubuli [3] und sind essentiell für die Aktivierbarkeit des Kanals [3]. Eine Verdopplung dieser AR-Domäne in NOMPC führt zu einem Kanal mit 58 ARs, NOMPC29+29AR [3]. Ob und wie diese Verdopplung die Kraftweiterleitung zum und vom MET Kanal beeinflusst ist bisher unbekannt.

Hypothesis:Nitinol is a suitable material for passive middle ear prosthesis.Background:In modern ear microsurgery, the restitution of hearing is tremendously important. In passive ossicular reconstruction, rigid alloplastic materials are widespread in use. However, rigid prostheses fail to adapt to atmospheric pressure changes. We describe the use of the super-elastic material nitinol in passive ossicular reconstruction to overcome this limitation.Methods:Together with an industrial partner, we developed a nitinol clip prosthesis equipped with a flexible prosthesis headplate. The new prosthesis was evaluated for flexibility and its sound transmission properties were compared with standard clip prostheses. For this purpose, the sound-induced acceleration of the stapes footplate was measured by laser-doppler vibrometry in temporal bones. Furthermore, the flexibility of the prosthesis plate was tested in a load-cell experiment.Results:On average, the pure tone transmission characteristics of the nitinol prosthesis is statistically not distinguishable from standard titanium clip prostheses. The tests in the load cell confirmed the flexibility of the prosthesis. Any measured prosthesis returns to its original state after deformation.Conclusion:The newly developed nitinol clip prosthesis shows similar sound transmission properties in comparison to established prostheses with high flexibility indicating a step forward to a physiological ossicular chain reconstruction.

Einleitung In der passiven Mittelohrprothetik stellen starre, alloplastische Materialien den Standard dar. Während diese Materialen gute Schallleitungseigenschaften aufweisen, sind sie weniger gut geeignet um atmosphärische Druckschwankungen auszugleichen. Hier könnten superelastische Materialien, wie z.B. Nitinol, eine valide Alternative darstellen.

In recent years, genetics, physiology, and structural biology have advanced into the molecular details of the sensory physiology of auditory hair cells.Inner hair cells (IHCs) and outer hair cells (OHCs) mediate two key functions: active amplification and nonlinear compression of cochlear vibrations by OHCs and sound encoding by IHCs at their afferent synapses with the spiral ganglion neurons.OHCs and IHCs share some molecular physiology, e.g.mechanotransduction at the apical hair bundles, ribbon-type presynaptic active zones, and ionic conductances in the basolateral membrane.Unique features enabling their specific function include prestin-based electromotility of OHCs and indefatigable transmitter release at the highest known rates by ribbon-type IHC active zones.Despite their compact morphology, the molecular machineries that either generate electrical signals or are driven by these signals are essentially all segregated into local subcellular structures.This review provides a brief account on recent insights into the molecular physiology of cochlear hair cells with a specific focus on organization into membrane domains.

Purpose Cone Beam Computed Tomography (CBCT) offers a valid alternative to conventional Computed Tomography (CT). A possible radiation dose reduction with the use of CBCT in postoperative imaging of CIs is of great importance. Whether the visualization of Cochlear Implant (CI) electrodes in CBCT correlates with the radiation dose applied was investigated in this study. Methods We compared the visualization quality of Contour Advance CIs to Straight CIs from Cochlear using CBCT with varying tube parameters on whole-head specimen. Results The internal diameter of the cochlea decreases from base to apex, resulting in a significantly different intracochlear positioning of the two tested CI models. While electrodes of the Contour Advance series are located close to the modiolus, thus closer to the spiral ganglion neurons, those of the Straight series are located further away. The artifact portion of the electrode amounts to 50–70% of the radiological diameter of the electrode. An increase in artifact portion from the base (electrode #1 approx. 50%) to the apex (electrode #20 approx. 70%) of the cochlea was observed. The visualization of electrodes in the medial and apical part of the cochlea is limited due to artifact overlapping. There was no correlation between the artifact size and the applied radiation dose. Conclusion The results indicate that a reduction of the radiation dose by up to 45% of the currently applied radiation dose of standard protocols would be possible. Investigations of the effects on subjective image quality still need to be performed.

Sensitive hearing in the fruit fly, Drosophila melanogaster, requires the NOMPC (TRPN1) channel [1]. NOMPC is a bona fide mechano-electrical transduction (MET) channel that possesses a domain consisting of 29 ankyrin repeats (ARs). These 29 ARs assemble into a helix [2], tether the channel intracellularly to microtubules [3], and are essential for mechano-gating [3].

Introduction Rigid alloplastic materials are the standard in passive middle ear prostheses. While these materials have good sound transmission properties, they are less suitable for compensating for atmospheric pressure fluctuations. Superelastic materials such as Nitinol could be a valid alternative.

Hearing utilizes sensory cells, hair cells, to translate mechanical stimuli into electro/chemical signals, termed mechano-electrical transduction (MET). MET occurs in the sensory organelle of hair cells, the hair bundle. An auditory hair bundle consists of three rows of stereocilia that are arranged in a staircase pattern. Positive deflections open MET channels, depolarizing the cell, resulting in a graduated neurotransmitter release. Hair bundle deflection could gate the MET channel via a chain of protein/protein interactions or via a force relay through the cell membrane.