Development of Mathematical Models of a Human Virtual Ear

L’orecchio umano è un complesso sistema biomeccanico deputato alla ricezione e percezione del suono. Il presente lavoro di tesi verte sull’analisi delle parti esterna o media. Sono introdotti alcuni cenni di anatomia dell’orecchio esterno e medio ed una indagine di letteratura rivolta alla modellazione. È stato sviluppato un modello ad elementi finiti standard e generalizzati del canale uditivo e della membrana timpanica, a seguito di un approfondito confronto tra modelli di letteratura della membrana timpanica. Per la catena ossiculare, comprensiva di giunti, legamenti e tendini muscolari che la supportano, è stato adottato un approccio di tipo multibody. Il modello ad elementi finiti della membrana timpanica è stato combinato con il modello multibody della catena ossiculare al fine di ottenere un modello ibrido dell’orecchio medio. L’elaborazione dell’informazione nel sistema uditivo è un tema centrale della psicoacustica, una branca dell’acustica concernente la correlazione quantitativa delle grandezze fisiche e della percezione del suono. Un approccio psicoacustico è stato applicato in un’attività sperimentale e teorica per la valutazione del rumore da alzacristalli elettrici, nell’ambito di un progetto in collaborazione con un’azienda del territorio. The present thesis mainly focuses on the outer and middle parts of the human ear, which is a complex biomechanical system, devoted to sound reception and perception. The anatomy in brief and a model-oriented review of outer and middle ear are introduced. A model including the auditory canal and the tympanic membrane was developed applying standard and generalized finite element methods, following a thorough comparison between literature finite element models of the tympanic membrane. The multibody approach was adopted for the ossicular chain and supporting structures (joints, ligaments and muscle tendons). The tympanic membrane finite element model and the ossicular chain multibody model were combined in a hybrid finite element-multibody model of the middle ear. The information processing in the auditory system is a central issue of the psychoacoustics, a branch of acoustics concerning the quantitative correlation between the physical characteristics of sounds and their perceptual attributes. The psychoacoustic approach was applied in an experimental and theoretical activity on power window noise evaluation, within a project in collaboration with a local enterprise

Regenerative therapies for tympanic membrane

It is estimated that by 2050 one in every ten people will be suffering from disabling hearing loss. Perforated tympanic membranes (TMs) are the most common injury to the human ear, resulting in a partial or complete hearing loss due to inept sound conduction. Commonly known as the eardrum, the TM is a thin, concave tissue of the middle ear that captures sound pressure waves from the environment and transmits them as mechanical vibrations to the inner ear. Microsurgical placement of autologous tissue graft has been the “gold standard” for treating damaged TMs; however, the incongruent structural and mechanical properties of these autografts often impair an optimal hearing restoration following recovery. Moreover, given the lack of available tissues for transplantations, regenerative medicine has emerged as a promising alternative. Several tissue engineered approaches applying bio-instructive scaffolds and stimuli have been reported for the TM regeneration, which can be broadly classified into TM repair and TM reconstruction. This review evaluates the current advantages and challenges of both strategies with a special focus on the use of recent biofabrication technologies for advancing TM tissue engineering

"Race for the Surface" : Competition between Bacteria and Host Cells in Implant Colonization Process

Prosthetic infection represents a major problem in the outcome of patients after implantation of a foreign body. The presence of biomaterial in the body provides a substratum to host either tissue-cell integration or bacterial colonization. In obliteration of an infected bone, artificial bone substitutes and rigid fixation materials are usually necessary to fill bone cavity and to restore the properties of the bone respectively. This study attempted to discover the effect of bioactive glass bone substitute granules (BAG) S53P4 on bacterial and human-cell adhesion on other implant used simultaneously (I, II). During development of new infection-resistant biomaterials, adherence and colonization of either bacterial cells or tissue cells on biomaterials must be evaluated in parallel. A methodology allowing study of the simultaneous growth of bacteria and tissue cells on the same biomaterial surface was developed. This will allow discovery of the effect of various bacterial concentrations on host-cell viability and integration with an implant surface, and their relation to increasing reactive oxygen species (ROS) levels and cell apoptosis (III). Finally, considering our first results and that microorganisms frequently infect an implant surface during surgery and start to compete for the surface before tissue integration, it was hypothesized that incubation of implants with host cells before implantation may be one way to reduce the bacterial living space available and would prevent bacterial adhesion and consequently the infection of biomaterials (IV). Bacterial and human osteoblast-like osteosarcoma cells (SaOS-2) or primary osteoblast (hOB) cells were incubated for 4.5 hours, 2 days, or 4 days at 37°C. As substratum, titanium (Ti), polytetrafluoroethylene (PTFE), polydimethyl-siloxane (PDMS), or bioactive glass plates (IV) were used. The study was done separately (I, II), in competition with SaOS-2 or hOB (III), or in competition with SaOS-2 after 24-hour pre-incubation with SaOS-2 (IV). The effect of BAG S53P4 on bacteria (I) and cell (II) adhesion was studied in either a normal atmosphere or in hypoxia-simulating atmospheric conditions of the middle ear, mastoid cavity, or sinuses. Human osteoblast-like SaOS-2 cells or primary osteoblast (hOB) cells (III) (both, 1x105cells/mL), and collection strains of Staphylococcus aureus and Staphylococcus epidermidis (I) [108 colony forming units (CFU) (I) or (serial 1:10 dilutions of 108 CFU (III, IV)] were employed. The bacteria and cell proliferation, cytotoxicity (III, IV), and production of reactive oxygen species (ROS) (III) were evaluated by colorimetric (MTT, LDH, and crystal violet) (III, IV) as well as by fluorometric methods (fluorescent microscopy and flow cytometry) (III). Bacterial cell viability was studied by use of a drop-plate method after sonication. Effects of BAG S53P4 on cell adhesion were linked intimately with modifications of cellular attachment organs (vinculin containing focal adhesions), rearrangement of the actin cytoskeleton, and cellular spreading. The presence of bioglass under normoxic and hypoxic conditions prevented bacterial and biofilm adhesion for most of the materials and promoted integration of SaOS-2 cells with various biomaterial surfaces, especially under hypoxic conditions, in which S53P4 granules cause increased pH (I, II). In the competitive study, the presence of bacteria resulted in reduced adherence of human cells to the surface of the biomaterials, increased production of ROS, and increased apoptosis. The presence of either type of human cell was associated with a reduction in bacteria compared with that for the materials incubated with S. aureus only (III). Pretreatment with human cells was also associated with a reduction in bacterial colonization of the biomaterial compared with that of the non-pretreated materials, but the presence of bacteria produced a decrease in viable human cells for all materials (IV). In conclusion, the presence of S53P4 granules may both protect implants from bacterial colonization and promote their osteointegration. In the presence of bacteria and cells, colonization of the surface by one reduces colonization by the other. The bacteria produce cellular oxidative stress in human cells, which may be related to the cellular death. The preoperative incubation of prostheses with host cells could be a new way to prevent infection of biomaterials and lessen the risk for bacterial antibiotic resistance

Determination of The Mechanical Properties of Guinea Pig Tympanic Membrane Using Combined Fringe Projection and Simulations

Measurement of the mechanical properties of guinea pig tympanic membrane (TM) with fringe projection and simulation. Fringe projection technique was used to provide optic access for measurement of the volume displacement of TM under different pressure levels. FEM model with hyperelastic constitute law was built to simulate the experimental procedure. Experimental data and simulation result were fitted to obtain the hyperelastic parameters of guinea pig TM. Hardening effects was observed through pressure- volume displacement curve. The stress- strain curve plotted based on the estimated mechanical properties was also reflect such phenomenon. Comparison between the positive and negative pressure loading from middle ear cavity indicate that, such hardening effect is stronger as negative pressure applied. The observation of the section profile of 3-D surface reconstruction of TM with Fringe projection technique shows that, the displacement around umbo is asymmetric. It means that the malleus tend to rotate rather than translate at high pressure level. The experimental design was compared with other research group. Full-field mechanical properties measured with the designed experiment were validated by comparison to existed data in literature.Mechanical & Aerospace Engineerin

Hearing Loss

Authored by 17 international researchers and research teams, the book provides up-to-date insights on topics in five different research areas related to normal hearing and deafness. Techniques for assessment of hearing and the appropriateness of the Mongolian gerbil as a model for age-dependent hearing loss in humans are presented. Parental attitudes to childhood deafness and role of early intervention for better treatment of hearing loss are also discussed. Comprehensive details are provided on the role of different environmental insults including injuries in causing deafness. Additionally, many genes involved in hearing loss are reviewed and the genetics of recessively inherited moderate to severe and progressive deafness is covered for the first time. The book also details established and evolving therapies for treatment of deafness

Modeling and Extraction of Transport Parameters to Simulate Drug Delivery in the Murine Cochlea

The usage of 1D and 3D models to simulate drug transport through the inner ear is a prominent method in cochlear fluid pharmacokinetics. However, the data used to create these models, is often based on invasive sampling methods that limit the spatial resolution given the size of the cochlear compartments within which solute can be measured. In this work by leveraging 3-D registered micro-Computed Tomography (μCT) scans of the murine cochlea that have been taken as iodinated contrast agent is delivered to it, we extract transport parameters and simulate a forward 1D model that allows variable and pulsatile delivery profiles over time and can be extended to the use of other drugs. Our 1D model may be used to simulate transport of a compound within the primary scalae or compartments of the cochlea namely: scala tympani (ST), scala vestibuli (SV) and scala media (SM). We investigate extracting transport parameters of the 1D model for the iodinated contrast agent (Iopamidol), such as the concentration dependent diffusion coefficient, along with permeabilities across membranes that represent transfer between the primary scalae and clearance out to blood. Flow rates that change over time are also learned, to account for leakage due to experimental set up. Dimensions of cochlear structures considered in the model, and empirical concentration profiles are extracted non-invasively over regional cross sections of a set of registered μCT scans of the mouse cochlea while an Iodinated contrast agent (Iopamidol) is delivered to it. Given initial estimates of the transport parameters, we use a simple iterative gradient descent approach to minimize the mean-squared error between our predicted concentrations from the 1D model and those derived empirically. We put forth a method to illustrate that once these parameters are learned for the contrast agent, they can be adjusted to simulate the delivery of other compounds, and can also be used to study various infusion paradigms to maintain a suitable therapeutic window for optimal, effective and safe administration of a drug. The results are important in the development of such paradigms for the prevention and treatment of acute and chronic types of hearing loss

Update On Hearing Loss

Update on Hearing Loss encompasses both the theoretical background on the different forms of hearing loss and a detailed knowledge on state-of-the-art treatment for hearing loss, written for clinicians by specialists and researchers. Realizing the complexity of hearing loss has highlighted the importance of interdisciplinary research. Therefore, all the authors contributing to this book were chosen from many different specialties of medicine, including surgery, psychology, and neuroscience, and came from diverse areas of expertise, such as neurology, otolaryngology, psychiatry, and clinical and experimental audiology