Flow-induced oscillations of vocal-fold replicas with tuned extensibility and material properties.

Human vocal folds are highly deformable non-linear oscillators. During phonation, they stretch up to 50% under the complex action of laryngeal muscles. Exploring the fluid/structure/acoustic interactions on a human-scale replica to study the role of the laryngeal muscles remains a challenge. For that purpose, we designed a novel in vitro testbed to control vocal-folds pre-phonatory deformation. The testbed was used to study the vibration and the sound production of vocal-fold replicas made of (i) silicone elastomers commonly used in voice research and (ii) a gelatin-based hydrogel we recently optimized to approximate the mechanics of vocal folds during finite strains under tension, compression and shear loadings. The geometrical and mechanical parameters measured during the experiments emphasized the effect of the vocal-fold material and pre-stretch on the vibration patterns and sounds. In particular, increasing the material stiffness increases glottal flow resistance, subglottal pressure required to sustain oscillations and vibratory fundamental frequency. In addition, although the hydrogel vocal folds only oscillate at low frequencies (close to 60 Hz), the subglottal pressure they require for that purpose is realistic (within the range 0.5-2 kPa), as well as their glottal opening and contact during a vibration cycle. The results also evidence the effect of adhesion forces on vibration and sound production.

Versatile fiber-reinforced hydrogels to mimic the microstructure and mechanics of human vocal-fold upper layers.

Human vocal folds are remarkable soft laryngeal structures that enable phonation due to their unique vibro-mechanical performances. These properties are tied to their specific fibrous architecture, especially in the upper layers, which comprise a gel-like composite called lamina propria. The lamina propria can withstand large and reversible deformations under various multiaxial loadings. Despite their importance, the relationships between the microstructure of vocal folds and their resulting macroscopic properties remain poorly understood. There is a need for versatile models that encompass their structural complexity while mimicking their mechanical features. In this study, we present a candidate model inspired by histological measurements of the upper layers of human vocal folds. Bi-photonic observations were used to quantify the distribution, orientation, width, and volume fraction of collagen and elastin fibers between histological layers. Using established biomaterials, polymer fiber-reinforced hydrogels were developed to replicate the fibrillar network and ground substance of native vocal fold tissue. To achieve this, jet-sprayed poly(ε-caprolactone) fibrillar mats were successfully impregnated with poly(L-lysine) dendrimers/polyethylene glycol hydrogels. The resulting composites exhibited versatile structural, physical and mechanical properties that could be customized through variations in the chemical formulation of their hydrogel matrix, the microstructural architecture of their fibrous networks (i.e., fiber diameter, orientation and volume fraction) and their assembly process. By mimicking the collagen network of the lamina propria with polymer fibers and the elastin/ground substance with the hydrogel composition, we successfully replicated the non-linear, anisotropic, and viscoelastic mechanical behavior of the vocal-fold upper layers, accounting for inter/intra-individual variations. The development of this mimetic model offers promising avenues for a better understanding of the complex mechanisms involved in voice production. STATEMENT OF SIGNIFICANCE: Human vocal folds are outstanding vibrating soft living tissues allowing phonation. Simple physical models that take into account the histological structure of the vocal fold and recapitulate its mechanical features are scarce. As a result, the relations between tissue components, organisation and vibro-mechanical performances still remain an open question. We describe here the development and the characterization of fiber-reinforced hydrogels inspired from the vocal-fold microstructure. These systems are able to reproduce the mechanics of vocal-fold tissues upon realistic cyclic and large strains under various multi-axial loadings, thus providing a mimetic model to further understand the impact of the fibrous network microstructure in phonation.

Cascading (3D) reconstruction procedure of composite structures from microtomography data.

Reconstruction of three-dimensional (3D) structure from experimental image acquisition (e.g., from micro computed tomography data) is very useful in composite material science. Composite considered are characterized by a dispersion of particles in a continuous phase. Many properties of the composite (e.g., mass transfer properties) depend on its structural assembly. A reliable prediction of these properties requires to well represent this structure and especially, the region at the vicinity of the dispersed phase. (3D) structure generation must thus permit to (1) simplify the real composite structure observed to make it compatible with further modelling tasks (e.g., meshing constraints in finite elements methods, computation time) and (2) keep enough representativeness of the structure of the specimen to produce reliable numerical predictions. This article describes an innovative, cascading (3D) reconstruction procedure of composite material from microtomography data.•First step of this pipeline is the extraction of relevant structural markers from microtomography images using image analysis.•Second step is the modelling of the distribution of the structural markers selected (statistical laws).•Third and final step is the reconstruction of the (3D) structures based on the pre-determined distribution laws in a RVE (representative volume element) of the composite.

Hybrid Silver Nanowire-CMC Aerogels: From 1D Nanomaterials to 3D Electrically Conductive and Mechanically Resistant Lightweight Architectures.

The directed assembly of nanomaterials into 3D architectures is a powerful tool to produce macroscopic materials with tailored physical properties. We show in this article that such a process can be advantageously performed for the fabrication of lightweight electrically conductive materials. Silver nanowire aerogels (AgNWAs) with very low densities (down to ∼6 mg cm-3) were ice-templated and freeze-dried, leading to 3D shaped cellular materials based on one-dimensional nanoscopic building blocks. Due to their intrinsic moderate mechanical resistance, the potential use of pure AgNWAs in real life applications appears rather limited. We demonstrate that the addition of carboxymethylcellulose (CMC) in a 1:1 weight ratio leads to the fabrication of hybrid aerogels with highly improved mechanical properties. The molecular weight of the CMC is shown to be a critical parameter to ensure a good dispersion of the AgNWs, and thus to reach excellent performances such as a very low resistivity (0.9 ± 0.2 Ω·cm at 99.2 vol % porosity). The combination of silver nanowires with CMC-700k results in a gain higher than 7100% of the Young's modulus, from 10.4 ± 0.9 kPa (at very low density, i.e., 12 mg cm-3) for the AgNWAs to 740 ± 40 kPa for the AgNW:CMC aerogel. Electromechanical characterizations allowed us to quantify the piezoelectric properties of these hybrid aerogels. The very good elasticity and the piezoelectric behavior stability up to 100 cycles of compression under high (50%) deformation were revealed, which may be of interest for various applications such as pressure sensors.

A micro-mechanical model for the fibrous tissues of vocal folds.

Composed of collagen, elastin and muscular fibrous networks, vocal folds are soft laryngeal multi-layered tissues owning remarkable vibro-mechanical performances. However, the impact of their histological features on their overall mechanical properties still remains elusive. Thereby, this study presents a micro-mechanical hyperelastic model able to describe the 3D fibrous architecture and the surrounding matrices of the vocal-fold sublayers, and to predict their mechanical behavior. For each layer, the model parameters were identified using available histo-mechanical data, including their quasi-static response for key physiological loading paths, i.e., longitudinal tension, transverse compression and longitudinal shear. Regardless of the loading path, it is shown how macroscale nonlinear, anisotropic tissue responses are inherited from the fiber scale. Scenarios of micro-mechanisms are predicted, highlighting the major role of 3D fiber orientation in tension, steric hindrance in compression, and matrix contribution in shear. Finally, combining these predictions to vibrating hyperelastic Timoshenko beam's theory, the impact of the fibrous architecture of the upper layers on vocal-fold vibratory properties is emphasized.

Individual fibre separation in 3D fibrous materials imaged by X-ray tomography.

Modelling the physical behaviour of fibrous materials still remains a great challenge because it requires to evaluate the inner structure of the different phases at the phase scale (fibre or matrix) and the at constituent scale (fibre). X-ray computed tomography (CT) imaging can help to characterize and to model these structures, since it allows separating the phases, based on the grey level of CT scans. However, once the fibrous phase has been isolated, automatically separating the fibres from each other is still very challenging. This work aims at proposing a method which allows separating the fibres and localizing the fibre-fibre contacts for various fibres geometries, that is: straight or woven fibres, with circular or non-circular cross sections, in a way that is independent of the fibres orientations. This method uses the local orientation of the structure formed by the fibrous phase and then introduces the misorientation angle. The threshold of this angle is the only parameter required to separate the fibres. This paper investigates the efficiency of the proposed algorithm in various conditions, for instance by changing the image resolution or the fibre tortuosity on synthetic images. Finally, the proposed algorithm is applied to real images or samples made up of synthetic solid fibres.

Mechanics of gelatin-based hydrogels during finite strain tension, compression and shear.

Introduction: Among the biopolymers used to make hydrogels, gelatin is very attractive due to its biocompatibility, biodegradability and versatile physico-chemical properties. A proper and complete characterization of the mechanical behavior of these hydrogels is critical to evaluate the relevance of one formulation over another for a targeted application, and to optimise their processing route accordingly. Methods: In this work, we manufactured neat gelatin and gelatin covalently cross-linked with glutaraldehyde at various concentrations, yielding to hydrogels with tunable mechanical properties that we characterized under finite strain, cyclic tension, compression and shear loadings. Results and Discussion: The role of both the chemical formulation and the kinematical path on the mechanical performances of the gels is highlighted. As an opening towards biomedical applications, the properties of the gels are confronted to those of native soft tissues particularly complicated to restore, the human vocal folds. A specific cross-linked hydrogel is selected to mimic vocal-fold fibrous tissues.

Mechanics of human vocal folds layers during finite strains in tension, compression and shear.

During phonation, human vocal fold tissues are subjected to combined tension, compression and shear loading modes from small to large finite strains. Their mechanical behaviour is however still not well understood. Herein, we complete the existing mechanical database of these soft tissues, by characterising, for the first time, the cyclic and finite strains behaviour of the lamina propria and vocalis layers under these loading modes. To minimise the inter or intra-individual variability, particular attention was paid to subject each tissue sample successively to the three loadings. A non-linear mechanical behaviour is observed for all loading modes: a J-shape strain stiffening in longitudinal tension and transverse compression, albeit far less pronounced in shear, stress accommodation and stress hysteresis whatever the loading mode. In addition, recorded stress levels during longitudinal tension are much higher for the lamina propria than for the vocalis. Conversely, the responses of the lamina propria and the vocalis in transverse compression as well as transverse and longitudinal shears are of the same orders of magnitude. We also highlight the strain rate sensitivity of the tissues, as well as their anisotropic properties.

Does the Knowledge of the Local Thickness of Human Ascending Thoracic Aneurysm Walls Improve Their Mechanical Analysis?

Ascending thoracic aortic aneurysm (ATAA) ruptures are life threatening phenomena which occur in local weaker regions of the diseased aortic wall. As ATAAs are evolving pathologies, their growth represents a significant local remodeling and degradation of the microstructural architecture and thus their mechanical properties. To address the need for deeper study of ATAAs and their failure, it is required to analyze the mechanical behavior at the sub-millimeter scale by making use of accurate geometrical and kinematical measurements during their deformation. For this purpose, we propose a novel methodology that combined an accurate tool for thickness distribution measurement of the arterial wall, digital image correlation to assess local strain fields and bulge inflation to characterize the physiological and failure response of flat unruptured human ATAA specimens. The analysis of the heterogeneity of the local thickness and local physiological stress and strain was carried out for each investigated subject. At the subject level, our results state the presence of a non-consistent relationship between the local wall thickness and the local physiological strain field and high heterogeneity of the variables. At the inter-subject level, thicknesses were studied in relation to physiological strain and stress and load at rupture. The rupture pressure was correlated with neither the average thickness nor the lowest thickness of the specimens. Our results confirm that intrinsic material strength (hence structure) differs a lot from a subject to another and even within the same subject.

3D multiscale imaging of human vocal folds using synchrotron X-ray microtomography in phase retrieval mode.

Human vocal folds possess outstanding abilities to endure large, reversible deformations and to vibrate up to more than thousand cycles per second. This unique performance mainly results from their complex specific 3D and multiscale structure, which is very difficult to investigate experimentally and still presents challenges using either confocal microscopy, MRI or X-ray microtomography in absorption mode. To circumvent these difficulties, we used high-resolution synchrotron X-ray microtomography with phase retrieval and report the first ex vivo 3D images of human vocal-fold tissues at multiple scales. Various relevant descriptors of structure were extracted from the images: geometry of vocal folds at rest or in a stretched phonatory-like position, shape and size of their layered fibrous architectures, orientation, shape and size of the muscle fibres as well as the set of collagen and elastin fibre bundles constituting these layers. The developed methodology opens a promising insight into voice biomechanics, which will allow further assessment of the micromechanics of the vocal folds and their vibratory properties. This will then provide valuable guidelines for the design of new mimetic biomaterials for the next generation of artificial larynges.

Cellulose crystals plastify by localized shear.

Cellulose microfibrils are the principal structural building blocks of wood and plants. Their crystalline domains provide outstanding mechanical properties. Cellulose microfibrils have thus a remarkable potential as eco-friendly fibrous reinforcements for structural engineered materials. However, the elastoplastic properties of cellulose crystals remain poorly understood. Here, we use atomistic simulations to determine the plastic shear resistance of cellulose crystals and analyze the underpinning atomic deformation mechanisms. In particular, we demonstrate how the complex and adaptable atomic structure of crystalline cellulose controls its anisotropic elastoplastic behavior. For perfect crystals, we show that shear occurs through localized bands along with noticeable dilatancy. Depending on the shear direction, not only noncovalent interactions between cellulose chains but also local deformations, translations, and rotations of the cellulose macromolecules contribute to the response of the crystal. We also reveal the marked effect of crystalline defects like dislocations, which decrease both the yield strength and the dilatancy, in a way analogous to that of metallic crystals.

Patient-specific simulation of endovascular repair surgery with tortuous aneurysms requiring flexible stent-grafts.

The rate of post-operative complications is the main drawback of endovascular repair, a technique used to treat abdominal aortic aneurysms. Complex anatomies, featuring short aortic necks and high vessel tortuosity for instance, have been proved likely prone to these complications. In this context, practitioners could benefit, at the preoperative planning stage, from a tool able to predict the post-operative position of the stent-graft, to validate their stent-graft sizing and anticipate potential complications. In consequence, the aim of this work is to prove the ability of a numerical simulation methodology to reproduce accurately the shapes of stent-grafts, with a challenging design, deployed inside tortuous aortic aneurysms. Stent-graft module samples were scanned by X-ray microtomography and subjected to mechanical tests to generate finite-element models. Two EVAR clinical cases were numerically reproduced by simulating stent-graft models deployment inside the tortuous arterial model generated from patient pre-operative scan. In the same manner, an in vitro stent-graft deployment in a rigid polymer phantom, generated by extracting the arterial geometry from the preoperative scan of a patient, was simulated to assess the influence of biomechanical environment unknowns in the in vivo case. Results were validated by comparing stent positions on simulations and post-operative scans. In all cases, simulation predicted stents deployed locations and shapes with an accuracy of a few millimetres. The good results obtained in the in vitro case validated the ability of the methodology to simulate stent-graft deployment in very tortuous arteries and led to think proper modelling of biomechanical environment could reduce the few local discrepancies found in the in vivo case. In conclusion, this study proved that our methodology can achieve accurate simulation of stent-graft deployed shape even in tortuous patient specific aortic aneurysms and may be potentially helpful to help practitioners plan their intervention.

Reversible dilatancy in entangled single-wire materials.

Designing structures that dilate rapidly in both tension and compression would benefit devices such as smart filters, actuators or fasteners. This property however requires an unusual Poisson ratio, or Poisson function at finite strains, which has to vary with applied strain and exceed the familiar bounds: less than 0 in tension and above 1/2 in compression. Here, by combining mechanical tests and discrete element simulations, we show that a simple three-dimensional architected material, made of a self-entangled single long coiled wire, behaves in between discrete and continuum media, with a large and reversible dilatancy in both tension and compression. This unusual behaviour arises from an interplay between the elongation of the coiled wire and rearrangements due to steric effects, which, unlike in traditional discrete media, are hysteretically reversible when the architecture is made of an elastic fibre.

Patient-specific numerical simulation of stent-graft deployment: Validation on three clinical cases.

Endovascular repair of abdominal aortic aneurysms faces some adverse outcomes, such as kinks or endoleaks related to incomplete stent apposition, which are difficult to predict and which restrain its use although it is less invasive than open surgery. Finite element simulations could help to predict and anticipate possible complications biomechanically induced, thus enhancing practitioners' stent-graft sizing and surgery planning, and giving indications on patient eligibility to endovascular repair. The purpose of this work is therefore to develop a new numerical methodology to predict stent-graft final deployed shapes after surgery. The simulation process was applied on three clinical cases, using preoperative scans to generate patient-specific vessel models. The marketed devices deployed during the surgery, consisting of a main body and one or more iliac limbs or extensions, were modeled and their deployment inside the corresponding patient aneurysm was simulated. The numerical results were compared to the actual deployed geometry of the stent-grafts after surgery that was extracted from postoperative scans. We observed relevant matching between simulated and actual deployed stent-graft geometries, especially for proximal and distal stents outside the aneurysm sac which are particularly important for practitioners. Stent locations along the vessel centerlines in the three simulations were always within a few millimeters to actual stents locations. This good agreement between numerical results and clinical cases makes finite element simulation very promising for preoperative planning of endovascular repair.

Deployment of stent grafts in curved aneurysmal arteries: toward a predictive numerical tool.

The mechanical behavior of aortic stent grafts plays an important role in the success of endovascular surgery for aneurysms. In this study, finite element analysis was carried out to simulate the expansion of five marketed stent graft iliac limbs and to evaluate quantitatively their mechanical performances. The deployment was modeled in a simplified manner according to the following steps: (i) stent graft crimping and insertion in the delivery sheath, (ii) removal of the sheath and stent graft deployment in the aneurysm, and (iii) application of arterial pressure. In the most curved aneurysm and for some devices, a decrease of stent graft cross-sectional area up to 57% was found at the location of some kinks. Apposition defects onto the arterial wall were also clearly evidenced and quantified. Aneurysm inner curve presented significantly more apposition defects than outer curve. The feasibility of finite element analysis to simulate deployment of marketed stent grafts in curved aneurysm models was demonstrated. The study of the influence of aneurysm tortuosity on stent graft mechanical behavior shows that increasing vessel curvature leads to stent graft kinks and inadequate apposition against the arterial wall. Such simulation approach opens a very promising way toward surgical planning tools able to predict intra and/or post-operative short-term stent graft complications.

Mechanical behaviour of a fibrous scaffold for ligament tissue engineering: finite elements analysis vs. X-ray tomography imaging.

The use of biodegradable scaffolds seeded with cells in order to regenerate functional tissue-engineered substitutes offers interesting alternative to common medical approaches for ligament repair. Particularly, finite element (FE) method enables the ability to predict and optimise both the macroscopic behaviour of these scaffolds and the local mechanic signals that control the cell activity. In this study, we investigate the ability of a dedicated FE code to predict the geometrical evolution of a new braided and biodegradable polymer scaffold for ligament tissue engineering by comparing scaffold geometries issued from FE simulations and from X-ray tomographic imaging during a tensile test. Moreover, we compare two types of FE simulations the initial geometries of which are issued either from X-ray imaging or from a computed idealised configuration. We report that the dedicated FE simulations from an idealised reference configuration can be reasonably used in the future to predict the global and local mechanical behaviour of the braided scaffold. A valuable and original dialog between the fields of experimental and numerical characterisation of such fibrous media is thus achieved. In the future, this approach should enable to improve accurate characterisation of local and global behaviour of tissue-engineering scaffolds.

Finite element analysis of the mechanical performances of 8 marketed aortic stent-grafts.

PURPOSE: To assess numerically the flexibility and mechanical stresses undergone by stents and fabric of currently manufactured stent-grafts. METHODS: Eight marketed stent-graft limbs (Aorfix, Anaconda, Endurant, Excluder, Talent, Zenith Flex, Zenith LP, and Zenith Spiral-Z) were modeled using finite element analysis. A numerical benchmark combining bending up to 180° and pressurization at 150 mmHg of the stent-grafts was performed. Stent-graft flexibility, assessed by the calculation of the luminal reduction rate, maximal stresses in stents, and maximal strains in fabric were assessed. RESULTS: The luminal reduction rate at 90° was <20% except for the Talent stent-graft. The rate at 180° was higher for Z-stented models (Talent, Endurant, Zenith, and Zenith LP; range 39%-78%) than spiral (Aorfix, Excluder, and Zenith Spiral-Z) or circular-stented (Anaconda) devices (range 14%-26%). At 180°, maximal stress was higher for Z-stented stent-grafts (range 370-622 MPa) than spiral or circular-stented endografts (range 177-368 MPa). At 90° and 180°, strains in fabric were low and did not differ significantly among the polyester stent-grafts (range 0.5%-7%), while the expanded polytetrafluoroethylene fabric of the Excluder stent-graft underwent higher strains (range 11%-18%). CONCLUSION: Stent design strongly influences mechanical performances of aortic stent-grafts. Spiral and circular stents provide greater flexibility, as well as lower stress values than Z-stents, and thus better durability.

Severe bending of two aortic stent-grafts: an experimental and numerical mechanical analysis.

Stent-grafts (SGs) are commonly used for treating abdominal aortic aneurysms (AAAs) and numerical models tend to be developed for predicting the biomechanical behavior of these devices. However, due to the complexity of SGs, it is important to validate the models. In this work, a validation of the numerical model developed in Demanget et al. (J. Mech. Behav. Biomed. Mater. 5:272-282, 2012) is presented. Two commercially available SGs were subjected to severe bending tests and their 3D geometries in undeformed and bent configurations were imaged from X-ray microtomography. Dedicated image processing subroutines were used in order to extract the stent centerlines from the 3D images. These skeletons in the undeformed configurations were used to set up SG numerical models that are subjected to the boundary conditions measured experimentally. Skeletons of imaged and deformed stents were then quantitatively compared to the numerical simulations. A good agreement is found between experiments and simulations. This validation offers promising perspectives to implementing the numerical models in a computer-aided tool and simulating the endovascular treatments.