Engineering a 3D-Bioprinted Model of Human Heart Valve Disease Using Nanoindentation-Based Biomechanics

In calcific aortic valve disease (CAVD), microcalcifications originating from nanoscale calcifying vesicles disrupt the aortic valve (AV) leaflets, which consist of three (biomechanically) distinct layers: the fibrosa, spongiosa, and ventricularis. CAVD has no pharmacotherapy and lacks in vitro models as a result of complex valvular biomechanical features surrounding resident mechanosensitive valvular interstitial cells (VICs). We measured layer-specific mechanical properties of the human AV and engineered a three-dimensional (3D)-bioprinted CAVD model that recapitulates leaflet layer biomechanics for the first time. Human AV leaflet layers were separated by microdissection, and nanoindentation determined layer-specific Young’s moduli. Methacrylated gelatin (GelMA)/methacrylated hyaluronic acid (HAMA) hydrogels were tuned to duplicate layer-specific mechanical characteristics, followed by 3D-printing with encapsulated human VICs. Hydrogels were exposed to osteogenic media (OM) to induce microcalcification, and VIC pathogenesis was assessed by near infrared or immunofluorescence microscopy. Median Young’s moduli of the AV layers were 37.1, 15.4, and 26.9 kPa (fibrosa/spongiosa/ventricularis, respectively). The fibrosa and spongiosa Young’s moduli matched the 3D 5% GelMa/1% HAMA UV-crosslinked hydrogels. OM stimulation of VIC-laden bioprinted hydrogels induced microcalcification without apoptosis. We report the first layer-specific measurements of human AV moduli and a novel 3D-bioprinted CAVD model that potentiates microcalcification by mimicking the native AV mechanical environment. This work sheds light on valvular mechanobiology and could facilitate high-throughput drug-screening in CAVD

First experience with a new stapes clip piston in stapedotomy

Objective: Hearing results after 23 implantations of a newly designed titanium-clip stapes piston prosthesis (the aWengen Clip Piston prosthesis) in patients with otosclerosis were evaluated. This new type of stapes piston was designed to avoid the crimping onto the incus in stapedotomy. This one clip fits all designs and enables solid fixation by clicking the prosthesis onto the long process of the incus without crimping. Study Design: A retrospective pilot study was carried out by microcomputer of the preoperative and postoperative audiological results of patients in whom the titanium-clip stapes piston prosthesis was implanted. Setting: Ear, nose and throat department of Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Patients: 23 Patients underwent a stapedotomy for hearing improvement suffering from otosclerosis. implantations of a newly designed titanium-clip stapes piston prosthesis (the aWengen Clip Piston prosthesis) in patients with otosclerosis were evaluated. Intervention(s): The stapedotomy was performed with the aWengen Clip Piston prosthesis. Main Outcome Measure(s): Pre and postoperative audiograms were used to evaluate the hearing gain improvement with the new stapes piston. Especially we looked at the airbone gap Closure and the sensorineural hearing after the surgical procedure and compared these with the ones before surgery. Results: The hearing results showed a closure of the pure-tone average air-bone gap to within 10 dB in 56.6% of cases (10 of 23 implantations) and to within 20 dB in 100% (23 of 23 implantations). A residual air-bone gap of greater than 20 dB was seen in the present pilot study. Postoperative overclosure of bone-conduction thresholds was discovered only for the frequency of 2 kHz. Sensorineural hearing loss greater than 10% did not occur, and there was no decline in the speech discrimination. Conclusions: The use of a newly designed titanium-clip stapes piston prosthesis with a diameter of 0.4 mm gives good results in cases of stapedotomy for otosclerosis. The titanium-clip design is a new development in the evolution of stapes piston prostheses. Surgical introduction, placement, and fixation are not always easy, depending on the anatomy of the middle ear and the thickness of the fixation area on the long process of the incu

Intracochlear misdirected implantation of a cochlear implant

This paper discusses a rare complication of an intracochlear misdirection of the electrode of a cochlear implant in a 55-year-old male. The patient received a cochlear implant using the mastoid-saving surgical approach. Intraoperative measurements showed impedance and NRT reactions suggesting a reasonable function of the inner ear and the implant. Postoperatively our patient suffered from passing vertigo. Postoperative CT scans revealed a misdirection implantation of the cochlear implant into the vestibular part of the inner ear. A deformed implant was removed and a reimplantation was successfully performed after enlarging and reshaping the cochleostomy. Our patient now enjoys all the benefits of an optimal functioning cochlear implant. Intracochlear misdirection of the electrode can occur even when intraoperative measurements seem to be normal. When a patient suffers from unexplained vertigo after cochlear implantation with a poor function of the implant a misdirection of the active electrode must be considered. New high resolution peroperative three-dimensional imaging techniques can probably help to avoid such insertion failure

What to do with the other ear after cochlear implantation

Unilateral cochlear implantation has become a widely accepted surgical intervention for both deaf children and adults. It is a reliable and effective method to rehabilitate profound deafness. Recently the benefits of the use of a contralateral hearing aid (bimodal stimulation) with a cochlear implant became clear. Bilateral cochlear implantation benefits bilateral input into the auditory system for adults and children. To provide the binaural advantages experienced by normal hearing subjects bilateral cochlear implantation or bimodal stimulation is probably indicated. Whether to choose between both possibilities depends on many factors. Cortical auditory evoked potential (CAEP) measurements can be an important tool to decide bilateral implantation in young children. Enough residual hearing in the non-implanted ear might benefit from bimodal stimulation. New protocols are needed for the audiological management for recipients of cochlear implant

How i do it : Modified Todd's meatoplasty

Background: Chronic otorrhoea after canal wall down mastoidectomy can be a clinical challenge. Basic principles for canal wall down surgery include establishing a large meatus. Several meatoplasty techniques have been reported. This paper describes this new indication for Todd's meatoplasty with surgical improvements. Study design: Retrospective review. Setting: Academic tertiary referral centre. Methods: Modifications of transposition postauricular flap meatoplasty are reported. This technique was applied in a series of patients with chronic otorrhoea after a canal wall down mastoidectomy. Results: In general, a dry radical cavity was successfully created within six weeks and follow-up visits at the out-patient clinic were reduced. Only minor complications occurred, which are all reported. Conclusion: The postauricular flap meatoplasty is a valuable tool in the management of chronic otorrhoea after an open cavity approach for cholesteatoma