Artificial Eardrum Research Articles

Manufacturing Radially Aligned PCL Nanofibers Reinforced With Sulfated Levan and Evaluation of its Biological Activity for Healing Tympanic Membrane Perforations.

The main objective of this study is to construct radially aligned PCL nanofibers reinforced with levan polymer and investigate their in vitro biological activities thoroughly. First Halomonas levan (HL) polysaccharide is hydrolyzed (hHL) and subjected to sulfation to attain Sulfated hydrolyzed Halomonas levan (ShHL)-based material indicating heparin mimetic properties. Then, optimization studies are carried out to produce coaxially generated radially aligned Poly(caprolactone) (PCL) -ShHL nanofibers via electrospinning. The obtained nanofibers are characterized with Fourier Transform Infrared Spectroscopy (FTIR)and Field Emission Scanning Electron Microscopy with Energy Dispersive X-Ray (FESEM-EDX) analysis, and mechanical, contact angle measurement, biodegradability, and swelling tests as well. Afterward, cytotoxicity of artificial tympanic membranes is analyzed by MTT (3-(4,5-Dimethylthiazol-2-yl) -2,5 Diphenyltetrazolium Bromide) test, and their impacts on cell proliferation, cellular adhesion, wound healing processes are explored. Furthermore, an additional FESEM imaging is performed to manifest the interactions between fibroblasts and nanofibers. According to analytical measurements it is detected that PCL-ShHL nanofibers i) are smaller in fiber diameter, ii) are more biodegradable, iii) are more hydrophilic, and iv) demonstrated superior mechanical properties compared to PCL nanofibers. Moreover, it is also deciphered that PCL-ShHL nanofibers strongly elevated cellular adhesion, proliferation, and in vitro wound healing features compared to PCL nanofibers. According to obtained results it is assumed that newly synthetized levan and PCL mediated nanofibers are very encouraging for healing tympanic membrane perforations.

Multichannel multimodal piezoelectric middle ear implant concept based on MEMS technology for next-generation fully implantable cochlear implant applications

This paper introduces a unique multimode, multichannel piezoelectric vibration sensor for the next-generation fully implantable cochlear implant (FICI) systems. The sensor, which can be implanted on the middle ear chain to collect and filter the ambient sound in eight frequency bands, comprises an array of 4 M-shape multimode and 11 single cantilevers. Finite element (FE) analysis indicates a 2.05-fold improvement in capturing frequency information for the multimodal sensor compared to its single-mode counterpart. Under an acoustic excitation at 100 dB SPL, the sensor, mounted on an artificial tympanic membrane, yielded a peak output voltage of 546.16 mVpp and a peak sensitivity of 285.28 mVpp/Pa at 1613 Hz. The extrapolated acoustic results indicated a dynamic frequency range between 300 Hz and 6 kHz, even at 30 dB SPL. Furthermore, a lightweight titanium coupler, employing a two-sided clipping structure with a maximum wall thickness of 70 μm, is micromachined for surgical attachment of the transducer to the middle ear chain. A commercial accelerometer, implanted on the incus short process (SP) of a cadaver using the titanium coupler, successfully recorded 0.1 g for 100 dB SPL at 500 Hz, revealing the potential feasibility of the coupler for vibration sensor implantation. Moreover, the presented anatomically accurate FE model of the middle ear, exhibiting a high correlation coefficient (R2) of 0.97 with the cadaveric experiment, suggests an efficient numerical approach for evaluating the implantation of middle ear prostheses. In this regard, the study holds great promise for clinical application in the field of implantable hearing aids.

Polyacrylamide/Gel-Based Self-Healing Artificial Tympanic Membrane for Drug Delivery of Otitis Treatment.

One of the bacterial infections caused by tympanic membrane perforation is otitis media (OM). Middle ear inflammation causes continuous pain and can be accompanied by aftereffects such as facial nerve paralysis if repeated chronically. Therefore, it is necessary to develop an artificial tympanic membrane (TM) that can effectively regenerate the eardrum due to the easy implantation and removal of OM inflammation. In this study, we synthesized hydrogel by mixing gelatin and polyacrylamide. Cefuroxime sodium salt was then incorporated into this hydrogel to both regenerate the TM and treat OM. Cytotoxicity experiments confirmed the biocompatibility of hydrogels equipped with antibiotics, and we conducted drug release and antibacterial experiments to examine continuous drug release. Through experiments, we have verified the excellent biocompatibility, drug release ability, and antibacterial effectiveness of hydrogel. It holds the potential to serve as an effective strategy for treating OM and regenerating TM as a drug delivery substance.

Applications of Graphene in Five Senses, Nervous System, and Artificial Muscles.

Graphene remains of great interest in biomedical applications because of biocompatibility. Diseases relating to human senses interfere with life satisfaction and happiness. Therefore, the restoration by artificial organs or sensory devices may bring a bright future by the recovery of senses in patients. In this review, we update the most recent progress in graphene based sensors for mimicking human senses such as artificial retina for image sensors, artificial eardrums, gas sensors, chemical sensors, and tactile sensors. The brain-like processors are discussed based on conventional transistors as well as memristor related neuromorphic computing. The brain-machine interface is introduced for providing a single pathway. Besides, the artificial muscles based on graphene are summarized in the means of actuators in order to react to the physical world. Future opportunities remain for elevating the performances of human-like sensors and their clinical applications.

Acoustic platforms meet MXenes - a new paradigm shift in the palette of biomedical applications.

The wide applicability of acoustics in the life of mankind spread over health, energy, environment, and others. These acoustic technologies rely on the properties of the materials with which they are made of. However, traditional devices have failed to develop into low-cost, portable devices and need to overcome issues like sensitivity, tunability, and applicability in biological in vivo studies. Nanomaterials, especially 2D materials, have already been proven to produce high optical contrast in photoacoustic applications. One such wonder kid in the materials family is MXenes, which are transition metal carbides, that are nowadays flourishing in the materials world. Recently, it has been demonstrated that MXene nanosheets and quantum dots can be synthesized by acoustic excitations. In addition, MXene can be used as a mechanical sensing material for building piezoresistive sensors to realize sound detection as it produces a sensitive response to pressure and vibration. It has also been demonstrated that MXene nanosheets show high photothermal conversion capability, which can be utilized in cancer treatment and photoacoustic imaging (PAI). In this review, we have rendered the role of acoustics in the palette of MXene, including acoustic synthetic strategies of MXenes, applications such as acoustic sensors, PAI, thermoacoustic devices, sonodynamic therapy, artificial ear drum, and others. The review also discusses the challenges and future prospects of using MXene in acoustic platforms in detail. To the best of our knowledge, this is the first review combining acoustic science in MXene research.

Two-stage amplification of an ultrasensitive MXene-based intelligent artificial eardrum.

We report an artificial eardrum using an acoustic sensor based on two-dimensional MXene (Ti3C2Tx), which mimics the function of a human eardrum for realizing voice detection and recognition. Using MXene with a large interlayer distance and micropyramid polydimethylsiloxane arrays can enable a two-stage amplification of pressure and acoustic sensing. The MXene artificial eardrum shows an extremely high sensitivity of 62 kPa−1 and a very low detection limit of 0.1 Pa. Notably, benefiting from the ultrasensitive MXene eardrum, the machine-learning algorithm for real-time voice classification can be realized with high accuracy. The 280 voice signals are successfully classified for seven categories, and a high accuracy of 96.4 and 95% can be achieved by the training dataset and the test dataset, respectively. The current results indicate that the MXene artificial intelligent eardrum shows great potential for applications in wearable acoustical health care devices.

Thin-Film PZT-Based Multi-Channel Acoustic MEMS Transducer for Cochlear Implant Applications

This paper presents a multi-channel acoustic transducer that works within the audible frequency range (250-5500 Hz) and mimics the operation of the cochlea by filtering incoming sound. The transducer is composed of eight thin film piezoelectric cantilever beams with different resonance frequencies. The transducer is well suited to be implanted in middle ear cavity with an active volume of 5 mm <inline-formula> <tex-math notation="LaTeX">$\times5$ </tex-math></inline-formula> mm <inline-formula> <tex-math notation="LaTeX">$\times0.62$ </tex-math></inline-formula> mm and mass of 4.8 mg. Resonance frequencies and piezoelectric outputs of the beams are modeled with Finite Element Method (FEM). Vibration experiments showed that the transducer is capable of generating up to 139.36 mV<inline-formula> <tex-math notation="LaTeX">$_{{\mathrm {pp}}}$ </tex-math></inline-formula> under 0.1 g excitation. Test results are consistent with the FEM model on frequency (97&#x0025;) and output voltage (89&#x0025;) values. Device was further tested with acoustic excitation on an artificial tympanic membrane and flexible substrate. Under acoustic excitation, 50.7 mV<inline-formula> <tex-math notation="LaTeX">$_{{\mathrm {pp}}}$ </tex-math></inline-formula> output voltage generated under 100 dB Sound Pressure Level (SPL). Output voltages observed in acoustical and mechanical characterizations are the highest values reported to the best of our knowledge. Finally, to assess the feasibility of the transducer in daily sound levels, it was excited with a speech sample and output signal was recovered. Time-domain waveforms of the recorded and recovered signals showed close patterns.

Submersion with grommets: contamination is possible at minimal depth, as demonstrated with a novel middle-ear model.

Advice to patients following grommet insertion and waterproofing can vary from clinician to clinician. A laboratory based experiment was performed to determine at what depth water contamination would occur through various grommet tubes. A novel experimental ear model was developed using an artificial tympanic membrane and ventilation tubes. Water contamination was identified using an effervescent solid that reacts when in contact with water. Measures of dispersion were used to describe the results. The average depth of water contamination was: 19.64 mm (range = 11-33 mm, standard deviation = 5.55 mm) using a Shepard grommet; 20.84 mm (range = 18-26 mm, standard deviation = 1.97 mm) with a titanium grommet; and 21.36 mm (range = 18-33 mm, standard deviation = 3.03 mm) using a T-tube. Water contamination was possible at depths of 11-33 mm. The average pressure at water effervescent activation was 0.20 kPa. Submersion underwater at any depth with grommets is likely to lead to middle-ear contamination. These findings are concordant with clinical studies.

Fabrication of tissue-engineered tympanic membrane patches using 3D-Printing technology

In recent years, scaffolds produced in 3D printing technology have become more widespread tool due to providing more advantages than traditional methods in tissue engineering applications. In this research, it was aimed to produce patches for the treatment of tympanic membrane perforations which caused significant hearing loss by using 3D printing method. Polylactic acid(PLA) scaffolds with Chitosan(CS) and Sodium Alginate(SA) added in various ratios were prepared for artificial eardrum patches. Different amounts of chitosan and sodium alginate added to PLA increased the biocompatibility of the produced scaffolds. The created patches were designed by mimicking the thickness of the natural tympanic membrane thanks to the precision provided by the 3D printed method. The produced scaffolds were analyzed separately for chemical, morphological, mechanical and biocompatibility properties. Scanning electron microscope (SEM), Fourier-transform infrared (FT-IR) spectroscopy was performed to observe the surface morphology and chemical structure of the scaffolds. Mechanical, thermal and physical properties, swelling and degradation behaviors were examined to fully analyze whole characteristic features of the samples. Cell culture study was also performed to demonstrate the biocompatibility properties of the fabricated scaffolds with human adipose tissue-derived mesenchymal stem cells (hAD-MSCs). 15 wt % PLA was selected as the control group and among all concentrations of CS and SA, groups containing 3 wt% CS and 3 wt% SA showed significantly superior and favorable features in printing quality. The research continued with these two scaffolds (3 wt% CS, and 3 wt% SA), which showed improved print quality when added to PLA. Overall, these results show that PLA/CS and PLA/SA 3D printed artificial patches have the potential to tissue engineering solutions to repair tympanic membrane perforation for people with hearing loss.

Hydrophilic/Hydrophobic Interphase-Mediated Bubble-like Stretchable Janus Ultrathin Films toward Self-Adaptive and Pneumatic Multifunctional Electronics

As promising candidates for intelligent biomimetic applications similar to living organisms, smart soft materials have aroused extensive interest due to their extraordinarily designable structures and functionality. Herein, a bubble-like elastomer-based electronic skin that can be pneumatically actuated is achieved through hydrophilic/hydrophobic interphase mediated asymmetric functionalization. The asymmetric and controllable introduction of elastic polydimethylsiloxane into the carbon nanotube film at the air/water interface can endow the Janus ultrathin film with tunable conductivity, self-adhesivity, self-adaptivity, and even self-sealing properties. As a result, the Janus films can be employed as multifunctional electronics, including self-adhesive strain sensing/thermal managing devices and even noncontact mechanical sensors as artificial eardrums for tiny air-pressure detection. Significantly, these excellent features can further enable the integration of actuating and sensing functions. As a proof of concept, the Janus film can serve as a self-supported device to simultaneously imitate the controllable contracting/expanding behaviors of the vocal sac of frog and monitor the real-time current change in this process, demonstrating significant potential in smart bionic applications.

Collagen-chitosan-glycerol bio-composite as artificial tympanic membrane for ruptured inner ear organ

WHO data in 2012 shows that 5.3% of world population highly suffers from hearing loss and deafness. One of the deafness causes is rupture of tympanic membrane. Tympanic membrane damage which occurs often is perforated tympanic membrane, and it is also commonly known in medical term as tympanic membrane perforation. The causes, for instance, are high frequency of using earphones, traumatic accidents, noise, bacteria, viruses, and infectious microorganism. Tympanoplasty becomes the only treatment that can be widely accepted despite of deficiencies in postoperative complications. Therefore, this research aims to create artificial tympanic membrane made of natural materials such as type I collagen composited with chitosan and made of addition of glycerol to improve its mechanical strength and biodegradability. The method included the process of dissolving acetic acid in distilled water and mixation with chitosan. The solution is next added with glycerol and stirred to be homogeneous. After that, it was minted in petri dish and aerated before characterized. The sample characterization included tensile strength of which tensile test results showed that the value of the elasticity modulus tended to decrease with an increase in collagen concentration. The elasticity modulus values in a row for the variations of 7: 3, 8: 2, and 9: 1 were 35.10 MPa, 54,52MPa, and 47,45MPa respectively. The morphological test with 1000x, 2500x, and 5000x magnification showed their interaction in the formation of pores. Cytotoxicity results, moreover, showed that those samples were non-toxic and safe for the body due to the percentage of living cells. The sound absorption coefficient was between 1000 Hz - 2000 Hz which means that it could use as sound absorbing material. The antibacterial test results showed that all the sample variations were anti-bacterial due to the diameter of the clear zone. In conclusion, collagen and chitosan composite with addition of glycerol could be used for potential artificial tympanic for to its characterization

Artificial eardrums get real

Three-dimensional printing can fabricate polymer scaffolds that mimic the orientation of collagen in the tympanic membrane.

Artificial eardrums get real

<xhtml:span xmlns:xhtml="http://www.w3.org/1999/xhtml" xml:lang="en">When combined with 3D printing, a decades-old technique can fabricate polymer scaffolds that support the tympanic membrane.</xhtml:span>

Outlook for Tissue Engineering of the Tympanic Membrane.

Tympanic membrane perforation is a common problem leading to hearing loss. Despite the autoregenerative activity of the eardrum, chronic perforations require surgery using different materials, from autologous tissue - fascia, cartilage, fat or perichondrium - to paper patch. However, both, surgical procedures (myringoplasty or tympanoplasty) and the materials employed, have a number of limitations. Therefore, the advances in this field are incorporating the principles of tissue engineering, which includes the use of scaffolds, biomolecules and cells. This discipline allows the development of new biocompatible materials that reproduce the structure and mechanical properties of the native tympanic membrane, while it seeks to implement new therapeutic approaches that can be performed in an outpatient setting. Moreover, the creation of an artificial tympanic membrane commercially available would reduce the duration of the surgery and costs. The present review analyzes the current treatment of tympanic perforations and examines the techniques of tissue engineering, either to develop bioartificial constructs, or for tympanic regeneration by using different scaffold materials, bioactive molecules and cells. Finally, it considers the aspects regarding the design of scaffolds, release of biomolecules and use of cells that must be taken into account in the tissue engineering of the eardrum. The possibility of developing new biomaterials, as well as constructs commercially available, makes tissue engineering a discipline with great potential, capable of overcoming the drawbacks of current surgical procedures.

The Evolution of Mastoidectomy and Tympanoplasty

A.D. 150 Galen describes incising “caries of the auditory meatus” 1363 Guy de Chauliac’s device to inspect ear by direct sunlight 1640 – Banzer uses pig bladder as artificial tympanic membrane 1646 Aural speculum by Hildanus 1653 Light microscope by Antony van Leeuwenhoek 1791 Death of Baron von Berger after mastoid trephination for tinnitus and deafness 1832 “Inspector Auris” by Thomas Buchanan 1846 Ether anesthesia by William Morton 1847Chloroform general anesthesia

Tympanic Membrane Regeneration Using a Water-Soluble Chitosan Patch

Chronic otitis media or tympanic membrane (TM) perforation is one of the most common otologic diseases. Surgical tympanoplasty remains the best treatment option despite the fact that paper patches are frequently used. Although paper patches are not biocompatible or effective, tympanoplasty is an expensive, complex surgery. Tissue engineering techniques offer a new treatment strategy for TM regeneration. In this study, novel tissue-engineered artificial eardrums were fabricated from water-soluble chitosan, which is known to be a good wound-healing biomaterial. The characteristics, cytotoxicity, and healing effects of several water-soluble chitosan patches (WSCPs) made using various concentrations of water-soluble chitosan and glycerol were investigated. The optimal WSCP was fabricated with 3% water-soluble chitosan and 3% glycerol, and it had a thickness of about 35 mum, a tensile strength of 7 MPa, a percent elongation of 101%, a hydrophilic surface, and no cytotoxicity. In vivo studies showed that the WSCPs were more effective than spontaneous healing for the repair of traumatic TM perforations. The healed TMs to which WSCPs were applied had a much higher density of collagen fibers and a better lamina propria layer structure than spontaneously healed TMs.

인조고막용 키토산 패치 지지체의 생체역학적 특성 및 독성 평가

The objectives of this study were to prepare a new artificial eardrum patch using water-insoluble chitosan for healing the tympanic membrane perforations and to investigate biomechanical properties and cyotoxicity of the chitosan patch scaffold (CPS). Tensile strength and elongation at the rupture point of CPSs were 2.49-74.05 MPa and 0.11-107.06%, respectively. As the biomechanical properties or CPSs varied with the concentration of chitosan and glycerol, the proper conditions for the CPS were found out. SEM analysis showed very smooth and uniform surface of CPSs without pores at x1000. The result of MTT test showed that CPSs had no cytotoxicity.

The artificial tympanic membrane (1840-1910): from brilliant innovation to quack device.

To present the rich and checkered history of the artificial eardrum, a widely used device in the 19th century, and to illustrate the behavior of otologists in response to the introduction of a promising new technology. Over 40 published books and articles spanning the years 1821 to 1909 in English, German, and French. DEVICE DESCRIPTIONS: A wide variety of devices were used to improve hearing and, purportedly, to reduce aural discharge. The most popular devices were made of gutta percha attached to a silver wire stem (Toynbee) and cotton balls with extraction cords (Yearsley). Other membranes included India rubber, lint, tin or silver foil, and even the vitelline membrane of an egg. Adhesion to the drum remnant was with saliva, water, petroleum jelly (Vaseline), or glycerin. Some were applied by the physician, whereas others were inserted daily by the patient, much as contact lenses are today. In several cases, the method of positioning an object over the drum remnant was actually invented by clever patients and then later adopted by practitioners. Once introduced, great optimism was generated about the "miraculous" value of this deafness cure. Petty jealousy among early inventors led to very public (and unprofessional) quarrels over the primacy of invention and bickering about whose device was superior. Over the subsequent decades, as more experience demonstrated the device's limited value, enthusiasm waned until otologists largely abandoned these devices around the turn of the last century. In the first two decades of the 20th century, artificial eardrums reached their peak of fame among the public when they were enthusiastically (and dishonestly) marketed by numerous quacks through newspaper advertisements as a universal cure for all forms of deafness. Only with the coming of the Food and Drug Administration did advertisements for US dollars 5 mail-order, medicated eardrums disappear from popular newspapers and magazines.

Diagnostic accuracy, tympanocentesis training performance, and antibiotic selection by pediatric residents in management of otitis media.

To assess the accuracy of pediatric residents in recognizing the physical examination findings of acute otitis media (AOM) and otitis media with effusion (OME), technical competence to perform tympanocentesis, and knowledge of guideline-recommended antibiotic management of AOM. A total of 383 pediatric residents from various programs in the United States viewed 9 different video-recorded pneumatic otoscopic examinations of tympanic membranes during a continuing medical education course. The ability to differentiate AOM, OME, and normal was ascertained. A mannequin of a child was used to assess technical proficiency of performing tympanocentesis on artificial tympanic membranes. A series of questions was posed regarding appropriate, pathogen-directed, second-line antibiotic selection for AOM. The average +/- standard deviation correct diagnosis on the otoscopic video examination was 41% +/- 16% (range: 19%-70%; median: 38%) by pediatric residents, tympanocentesis was optimally performed by 89%, and appropriate antibiotic therapy for drug-resistant Streptococcus pneumoniae was selected by 78% and appropriate therapy for beta-lactamase-producing Haemophilus influenzae was selected by 74%. According to this video-based examination, pediatric residents misdiagnose OME frequently. Pediatric residents have the skills to be trained to perform tympanocentesis. Approximately 75% of pediatric residents have knowledge of the appropriate antibiotics to select for treatment of resistant AOM pathogens. Interactive instruction with simulation technology may enhance skills and lead to improved diagnostic accuracy and treatment paradigms.

Assessing diagnostic accuracy and tympanocentesis skills in the management of otitis media.

The distinction between acute suppurative otitis media (AOM) and otitis media with effusion (OME) is important for antibiotic treatment decisions. Tympanocentesis may be useful in the diagnosis of AOM in selected patients. To assess physician accuracy in diagnosing AOM and OME from physical examination findings and technical competence in performing tympanocentesis. Five hundred fourteen pediatricians and 188 otolaryngologists viewed 9 different videotaped pneumatic otoscopic examinations of tympanic membranes during a continuing medical education course. Diagnostic differentiation of AOM, OME, and a normal tympanic membrane was ascertained. An infant mannequin model was used to assess the technical proficiency of performing tympanocentesis on artificial tympanic membranes. Overall, the average correct diagnosis by pediatricians was 50% (range, 25%-73%) and by otolaryngologists was 73% (range, 48%-88%). Pediatricians and otolaryngologists correctly recognized the absence of normality 89% to 100% and 93% to 100% of the time, respectively, but overdiagnosed AOM in 7% to 53% (mean, 27%) and in 3% to 23% (mean, 10%) of examinations. Performance of tympanocentesis was optimally performed by 89% of otolaryngologists and by 83% of pediatricians. The use of video-presented examinations to assess diagnostic ability suggests that AOM and OME may be misdiagnosed often. Interactive continuing medical education courses with simulation technology may enhance skills and improve diagnostic accuracy and treatment paradigms.