DS04 - Vie, santé et bien-être

From soft tissue's fibrous Microstructure to Voice biomechanics : towards the material design of a new biomimetic oscillator – MicroVoice

From soft tissue's fibrous Microstructure to Voice biomechanics : towards the material design of a new biomimetic oscillator

MicroVoice’s objective is to gain an in-depth understanding of the link between the micromechanics of vocal-fold tissues and their unique vibratory performances, and take the next step towards the development of new biomimetic oscillators. In the long term, MicroVoice will provide a solid framework for the innovative design of fibrous phonatory implants.

Phonatory biomechanics: a field of research to be developed

The study of human vocal production is complex because it involves many coupled phenomena, e.g. acoustic, aerodynamic and biomechanical phenomena. Today, compared to the knowledge acquired on the aero-acoustic characterization of human voice, the histological and biomechanical specificities of the vocal tissue are barely studied, and their impact on the remarkable vibratory properties of the vocal folds remains an open question. <br />In case of dysphonia, rehabilitation treatments in speech therapy are built on a strong know-how of the practitioners, continuously expecting an increase in fundamental knowledge to improve their clinical plans. Today, the durable restoration of the phonatory abilities of patients by injected biomaterials or artificial implants able to mimic the vibrations of the vocal folds remains a scientific, clinical and societal challenge. <br /> <br />Several issues explain the difficulty associated with the biomechanical study of vocal folds. Protected by laryngeal cartilages, they are indeed difficult to access by current medical imaging techniques. Due to their very small dimensions (<15mm), the implementation of ex vivo mechanical tests remains very delicate. There are in vitro simulators of the phonatory system, made up of artificial replicas of the vocal folds. But most of the model materials used are made up of homogeneous elastomers with isotropic microstructures and mechanical responses far from those experienced by the vocal folds. Thus, the different theoretical approaches to model the mechanical properties of laryngeal tissues have remained rather far from the physiological reality. Few theoretical proposals are made at the level of the constitutive fibers of the vocal tissue (collagen, elastin, muscle fibers). This multi-scale approach is essential to better understand the vibro-mechanical performance of vocal folds, and to develop the design of future biomimetic oscillators. The overall goal of the MicroVoice project is to fill this gap.

Since 2010, a few authors have started to investigate and model the vocal-tissue collagenous fibrous microstructure, opening a new insight into voice biomechanics. Based on these prior results, some clinical and mechanical arguments, MicroVoice’s key hypothesis is that the vibro-mechanical performances of vocal tissues are highly related to their fibrous microstructures and their surrounding matrices, and specifically: (i) to the nature of the major constitutive materials (collagen, elastin and muscle fibers, hyaluronic acid matrix), (ii) to the nature of their interactions, (iii) to their deformation and rearrangement micromechanisms.

Therefore, MicroVoice’s strategy is to develop a fibre’s scale approach to gain a better understanding of the link between the micromechanics of vibrating tissues and their macroscale performances. Several steps are planned in order to solve current issues:

i. to investigate the vocal-fold 3D fibrous architecture and micromechanics using synchrotron X-ray in situ microtomography, 2-photon microscopy and comparative histological analyses;
ii. to use these data for the mimetic design and process of new fibrous polymeric biomaterials with tailoring structural and biomechanical properties;
iii. to characterize the small/finite strains vibro-mechanical properties of the new composites at different scales (macro/micro) and frequencies (low/high), using Dynamic Mechanical Analysis and Laser Doppler Vibrometry.
iv. to validate their oscillating properties under “realistic” aero-acoustical and biophysic conditions using in vitro and ex vivo testbeds.

From an experimental point of view, promising data has recently been obtained on the 3D fibrous architecture of the vocal fold, thanks to high resolution images obtained by X-ray synchrotron microtomography at the ESRF (beamline ID19, Grenoble), and 2-photon confocal microscopy (Léon Bérard Research Center, Lyon). The comparison of these images with 2D histological sections validated both types of imaging and highlighted their complementarity.

Thanks to the bi-photonic microscopy, it was possible to differentiate, without staining, the networks of collagen and elastin on samples at rest. The distribution and organization of the two fibrillar proteins could thus be mapped over the length of the vocal cords (depth of 100 µm) showing their structural properties at zero load: preferential orientations, undulations, size, density.

Thanks to X-ray microtomography, tensile tests of vocal folds have also been imaged in situ. The analysis of these histomechanical data revealed: (i) at the tissue scale, a strongly nonlinear mechanical response, large anisotropic deformations induced by the hydro-mechanical couplings involved, and mechanical phenomena auxetic; (ii) at the level of the fibrous networks of the vocal muscle, a local rearrangement of the initially quasi-aligned fibrous structures, subjected to multiaxial deformations inducing fibre rotations and translations, which could be at the origin of the auxetic phenomena to the upper scale; (iii) at the level of the collagen / elastin networks of the upper layers (lamina propria), a deployment of the initially wavy fibers and a progressive reorientation in the direction of loading.

In parallel, first fibrous-reinforced hydrogels (based on gelatin, or polyethylene glycol and lysine dendrimers) have been proposed and are currently being evaluated.

Regarding the «biochemical formulations and shaping of materials« aspects, the composites proposed today within the framework of the project are elaborated in idealized geometries, to characterize the effect of the properties of the hydrogels (composition, molecular weight of the polymers) and fibrous reinforcements (diameter, porosity) on the mechanical behavior of the composites. As soon as a series of potential candidates is identified to reproduce the mechanical behavior of the vocal fold as closely as possible, the formulation of the composites in a realistic 3D form will be studied.

Regarding the «mechanical« aspects, the MicroVoice project is now focusing on the optimization of tools and methods for the vibratory study of soft composites with fibrous reinforcements at high and medium frequencies, a field of research still requiring experimental and theoretical developments.

T. Cochereau, H. Yousefi-Mashouf, L. Bailly, J. Sohier, L. Orgéas, N. Henrich Bernardoni, S. Rolland du Roscoat, A. McLeer-Florin, O. Guiraud (2019). “Vocal-fold 3D micro-architecture and micro-mechanics: a multimodal imaging study”. The 13th International Conference on Advances in Quantitative Laryngology, Voice and Speech Research, Jun 2019, Montréal, Canada.

A. Terzolo, T. Cochereau, L. Bailly, L. Orgéas, N. Henrich Bernardoni (2019). “Vocal fold visco-hyperelastic properties: characterization and multiscale modeling upon finite strains”. The 13th International Conference on Advances in Quantitative Laryngology, Voice and Speech Research (AQL 2019), Jun 2019, Montréal, Canada.

L. Bailly, F. Benboujja, L. Mongeau (2019). “Fundamentals of Bomedical Optics and Imaging”. Pre-conference workshop prior to the 13th International Conference on Advances in Quantitative Laryngology, Voice and Speech Research, Jun 2019, Montréal, Canada (invitation).

T. Cochereau, A. Terzolo, L. Bailly, L. Orgéas, N. Henrich Bernardoni, S. Rolland du Roscoat, A. McLeer-Florin (2018). “Human vocal-fold architecture and mechanical properties : 3D multiscale characterization and modelling”. 11th International Conference on Voice Physiology and Biomechanics (ICVPB 2018), Aug 2018, East Lansing, United States.

T. Cochereau (2019). “Human vocal fold structure and mechanics”. PhD Thesis, March 2019, Univ. Grenoble Alpes, France.

MicroVoice’s objective is to gain an in-depth understanding of the link between the micromechanics of vocal-fold tissues and their unique vibratory performances, and take the next step towards the development of new biomimetic oscillators. The strategy is:
i. to investigate the vocal-fold 3D fibrous architecture and micromechanics using unprecedented synchrotron X-ray in situ microtomography;
ii. to use these data to mimic and process fibrous biomaterials with tailored structural and biomechanical properties;
iii. to characterise the vibro-mechanical properties of these biomaterials at different scales (macro/micro) and frequencies (low/high), using Dynamic Mechanical Analysis and Laser Doppler Vibrometry.
iv. to validate their oscillating properties under “realistic” aero-acoustical conditions using in vitro and ex vivo testbeds.
MicroVoice will provide a solid framework for the innovative design of fibrous phonatory implants.

Project coordinator

Madame Lucie Bailly (Sols, solides, structures, risques)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

LADAF - Faculté de Médecine - UGA Laboratoire d'Anatomie des Alpes Françaises
3SR Sols, solides, structures, risques
GIPSA-lab Grenoble Image, Parole, Signal, Automatique
LBTI- CNRS Biologie Tissulaire et Ingénierie Thérapeutique

Help of the ANR 547,866 euros
Beginning and duration of the scientific project: - 48 Months

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