Amir K. Miri

Rapid Continuous Multimaterial Extrusion Bioprinting

The development of a multimaterial extrusion bioprinting platform is reported. This platform is capable of depositing multiple coded bioinks in a continuous manner with fast and smooth switching among different reservoirs for rapid fabrication of complex constructs, through digitally controlled extrusion of bioinks from a single printhead consisting of bundled capillaries synergized with programmed movement of the motorized stage.

Effects of dehydration on the viscoelastic properties of vocal folds in large deformations.

Dehydration may alter vocal fold viscoelastic properties, thereby hampering phonation. The effects of water loss induced by an osmotic pressure potential on vocal fold tissue viscoelastic properties were investigated. Porcine vocal folds were dehydrated by immersion in a hypertonic solution, and quasi-static and low-frequency dynamic traction tests were performed for elongations of up to 50%. Digital image correlation was used to determine local strains from surface deformations. The elastic modulus and the loss factor were then determined for normal and dehydrated tissues. An eight-chain hyperelastic model was used to describe the observed nonlinear stress-stretch behavior. Contrary to the expectations, the mass history indicated that the tissue absorbed water during cyclic extension when submerged in a hypertonic solution. During loading history, the elastic modulus was increased for dehydrated tissues as a function of strain. The response of dehydrated tissues was much less affected when the load was released. This observation suggests that hydration should be considered in micromechanical models of the vocal folds. The internal hysteresis, which is often linked to phonation effort, increased significantly with water loss. The effects of dehydration on the viscoelastic properties of vocal fold tissue were quantified in a systematic way. A better understanding of the role of hydration on the mechanical properties of vocal fold tissue may help to establish objective dehydration and phonotrauma criteria.

Nonlinear laser scanning microscopy of human vocal folds.

The purpose of this work was to apply nonlinear laser scanning microscopy (NLSM) for visualizing the morphology of extracellular matrix proteins within human vocal folds. This technique may potentially assist clinicians in making rapid diagnoses of vocal fold tissue disease or damage. Microstructural characterization based on NLSM provides valuable information for better understanding molecular mechanisms and tissue structure.

Mechanical characterization of vocal fold tissue: a review study.

Human vocal folds undergo self-sustaining oscillations during phonation. The phonatory functions of the vocal folds depend on their mechanical properties. This article presents a review of various mechanical testing methods and constitutive models that are currently in use for the characterization of mechanical properties of the vocal fold tissue. Special attention is given to tissue deformation under mechanical loading at different length scales. The wide range of elastic modulus values reported in the literature is discussed and justified using a multiscale perspective. This study aims to provide a better understanding of mechanical properties that can be used to build computational simulations of vocal fold vibrations and pave the way for the design of biomaterials to restore biomechanical properties in damaged vocal folds.

Indentation of poroviscoelastic vocal fold tissue using an atomic force microscope.

The elastic properties of the vocal folds (VFs) vary as a function of depth relative to the epithelial surface. The poroelastic anisotropic properties of porcine VFs, at various depths, were measured using atomic force microscopy (AFM)-based indentation. The minimum tip diameter to effectively capture the local properties was found to be 25µm, based on nonlinear laser scanning microscopy data and image analysis. The effects of AFM tip dimensions and AFM cantilever stiffness were systematically investigated. The indentation tests were performed along the sagittal and coronal planes for an evaluation of the VF anisotropy. Hertzian contact theory was used along with the governing equations of linear poroelasticity to calculate the diffusivity coefficient of the tissue from AFM indentation creep testing. The permeability coefficient of the porcine VF was found to be 1.80±0.32×10(-15)m(4)/Ns.

Microstructural characterization of vocal folds toward a strain-energy model of collagen remodeling

Collagen fibrils are believed to control the immediate deformation of soft tissues under mechanical load. Most extracellular matrix proteins remain intact during frozen sectioning, which allows them to be scanned using atomic force microscopy (AFM). Collagen fibrils are distinguishable because of their periodic roughness wavelength. In the present study, the shape and organization of collagen fibrils in dissected porcine vocal folds were quantified using nonlinear laser scanning microscopy data at the micrometer scale and AFM data at the nanometer scale. Rope-shaped collagen fibrils were observed. The geometric characteristics for the fibrils were fed into a hyperelastic model to predict the biomechanical response of the tissue. The model simulates the micrometer-scale unlocking behavior of collagen bundles when extended from their unloaded configuration. Force spectroscopy using AFM was used to estimate the stiffness of collagen fibrils (1±0.5MPa). The presence of rope-shaped fibrils is postulated to change the slope of the force-deflection response near the onset of nonlinearity. The proposed model could ultimately be used to evaluate changes in elasticity of soft tissues that result from the collagen remodeling.

Quantitative assessment of the anisotropy of vocal fold tissue using shear rheometry and traction testing

The human vocal folds are layered structures with intrinsically anisotropic elastic properties. Most testing methods assume isotropic behavior. Biaxial testing of vocal folds is strictly difficult because the very soft tissue tends to delaminate under transverse traction loads. In the present study, a linear transversely isotropic model was used to characterize the tissue in-vitro. Shear rheometry was used in conjunction with traction testing to quantify the elasticity of porcine vocal fold tissue. Uniaxial traction testing along with optical measurements were used to obtain the longitudinal modulus. The alternate vocal fold of each animal was subjected to a test-specific sample preparation and concurrently tested using dynamic shear rheometry. The stiffness ratio (i.e., the ratio of the longitudinal modulus and the transverse modulus) varied between ∼5 and ∼7 at low frequencies. The proposed methodology can be applied to other soft tissues.

Acoustic Radiation Force on a Spherical Contrast Agent Shell Near a Vessel Porous Wall – Theory

Contrast agent microshells (CAMSs) are under intensive investigation for their wide applications in biomedical imaging and drug delivery. In drug delivery applications, CAMSs are guided to the targeted site before fragmentation by high-intensity ultrasound waves leading to the drug release. Prediction of the acoustic radiation force used to nondestructively guide a CAMS to the suspected site is becoming increasingly important and gaining attention particularly because it increases the system efficiency. The goal of this work is to present a theoretical model for the time-averaged (static) acoustic radiation force experienced by a CAMS near a blood vessel wall. An exact solution for the scattering of normal incident plane acoustic waves on an air-filled elastic spherical shell immersed in a nonviscous fluid near a porous and nonrigid boundary is employed to evaluate the radiation force function (which is the radiation force per unit energy density per unit cross-sectional surface). A particular example is chosen to illustrate the behavior of the time-averaged (static) radiation force on an elastic polyethylene spherical shell near a porous wall, with particular emphasis on the relative thickness of the shell and the distance from its center to the wall. This proposed model allows obtaining a priori information on the static radiation force that may be used to advantage in related as drug delivery and contrast agent imaging. This study should assist in the development of improved models for the evaluation of the time-averaged acoustic radiation force on a cluster of CAMSs in viscous and heat-conducting fluids.

Microstructural and mechanical characterization of scarred vocal folds

The goal of this study was to characterize the vocal folds microstructure and elasticity using nonlinear laser scanning microscopy and atomic force microscopy-based indentation, respectively. As a pilot study, the vocal folds of fourteen rats were unilaterally injured by full removal of lamina propria; the uninjured folds of the same animals served as controls. The area fraction of collagen fibrils was found to be greater in scarred tissues two months after injury than the uninjured controls. A novel mathematical model was also proposed to relate collagen concentration and tissue bulk modulus. This work presents a first step towards systematic investigation of microstructural and mechanical characteristics in scarred vocal fold tissue.

Nanoscale viscoelasticity of extracellular matrix proteins in soft tissues: A multiscale approach.

It is hypothesized that the bulk viscoelasticity of soft tissues is determined by two length-scale-dependent mechanisms: the time-dependent response of the extracellular matrix (ECM) proteins at the nanometer scale and the biophysical interactions between the ECM solid structure and interstitial fluid at the micrometer scale. The latter is governed by poroelasticity theory assuming free motion of the interstitial fluid within the porous ECM structure. In a recent study (Heris, H.K., Miri, A.K., Tripathy, U., Barthelat, F., Mongeau, L., 2013. J. Mech. Behav. Biomed. Mater.), atomic force microscopy was used to measure the response of porcine vocal folds to a creep loading and a 50-nm sinusoidal oscillation. A constitutive model was calibrated and verified using a finite element model to accurately predict the nanoscale viscoelastic moduli of ECM. A generally good correlation was obtained between the predicted variation of the viscoelastic moduli with depth and that of hyaluronic acids in vocal fold tissue. We conclude that hyaluronic acids may regulate vocal fold viscoelasticity. The proposed methodology offers a characterization tool for biomaterials used in vocal fold augmentations.