A Viscoelastic Constitutive Framework for Aging Muscular and Elastic Arteries.

The evolution of arterial biomechanics and microstructure with age and disease plays a critical role in understanding the health and function of the cardiovascular system. Accurately capturing these adaptative processes and their effects on the mechanical environment is critical for predicting arterial responses. This challenge is exacerbated by the significant differences between elastic and muscular arteries, which have different structural organizations and functional demands. In this study, we aim to shed light to these adaptive processes by comparing the viscoelastic mechanics of autologous thoracic aortas (TA) and femoropopliteal arteries (FPA) in different age groups. We have extended our fractional viscoelastic framework, originally developed for FPA, to both types of arteries. To evaluate this framework, we analyzed experimental mechanical data from TA and FPA specimens from 21 individuals aged 13 to 73 years. Each specimen was subjected to a multi-ratio biaxial mechanical extension and relaxation test complemented by bidirectional histology to quantify the structural density and microstructural orientations. Our new constitutive model accurately captured the mechanical responses and microstructural differences of the tissues and closely matched the experimentally measured densities. It was found that the viscoelastic properties of collagen and smooth muscle cells (SMCs) in both the FPA and TA remained consistent with age, but the viscoelasticity of the SMCs in the FPA was twice that of the TA. Additionally, changes in collagen nonlinearity with age were similar in both TA and FPA. This model provides valuable insights into arterial mechanophysiology and the effects of pathological conditions on vascular biomechanics. STATEMENT OF SIGNIFICANCE: Developing durable treatments for arterial diseases necessitates a deeper understanding of how mechanical properties evolve with age in response to mechanical environments. In this work, we developed a generalized viscoelastic constitutive model for both elastic and muscular arteries and analyzed both the thoracic aorta (TA) and the femoropopliteal artery (FPA) from 21 donors aged 13 to 73. The derived parameters correlate well with histology, allowing further examination of how viscoelasticity evolves with age. Correlation between the TA and FPA of the same donors suggest that the viscoelasticity of the FPA may be influenced by the TA, necessitating more detailed analysis. In summary, our new model proves to be a valuable tool for studying arterial mechanophysiology and exploring pathological impacts.

Flexoelectric Enhancement of Strain Gradient Elasticity Across a Ferroelectric-to-Paraelectric Phase Transition.

We study the temperature dependent elastic properties of Ba0.8Sr0.2TiO3 freestanding membranes across the ferroelectric-to-paraelectric phase transition using an atomic force microscope. The bending rigidity of thin membranes can be stiffer compared to stretching due to strain gradient elasticity (SGE). We measure the Young's modulus of freestanding Ba0.8Sr0.2TiO3 drumheads in bending and stretching dominated deformation regimes on a variable temperature platform, finding a peak in the difference between the two Young's moduli obtained at the phase transition. This demonstrates a dependence of SGE on the dielectric properties of a material and alludes to a flexoelectric origin of an effective SGE.

Nonlinear Elasticity of Blood Vessels and Vascular Grafts.

The transplantation of vascular grafts has emerged as a prevailing approach to address vascular disorders. However, the development of small-diameter vascular grafts is still in progress, as they serve in a more complicated mechanical environment than their counterparts with larger diameters. The biocompatibility and functional characteristics of small-diameter vascular grafts have been well developed; however, mismatch in mechanical properties between the vascular grafts and native arteries has not been accomplished, which might facilitate the long-term patency of small-diameter vascular grafts. From a point of view in mechanics, mimicking the nonlinear elastic mechanical behavior exhibited by natural blood vessels might be the state-of-the-art in designing vascular grafts. This review centers on elucidating the nonlinear elastic behavior of natural blood vessels and vascular grafts. The biological functionality and limitations associated with as-reported vascular grafts are meticulously reviewed and the future trajectory for fabricating biomimetic small-diameter grafts is discussed. This review might provide a different insight from the traditional design and fabrication of artificial vascular grafts.

Uniformity of anti-plane stresses inside a nonlinear elastic elliptical or parabolic inhomogeneity.

We study the anti-plane strain problem associated with a p-Laplacian nonlinear elastic elliptical inhomogeneity embedded in an infinite linear elastic matrix subjected to uniform remote anti-plane stresses. A full-field exact solution is derived using complex variable techniques. It is proved that the stress field inside the elliptical inhomogeneity is nevertheless uniform. The uniformity of stresses is also observed inside a p-Laplacian nonlinear elastic parabolic inhomogeneity.

Accretion-ablation mechanics.

In this paper, we formulate a geometric nonlinear theory of the mechanics of accreting-ablating bodies. This is a generalization of the theory of accretion mechanics of Sozio & Yavari (Sozio & Yavari 2019 J. Nonlinear Sci. 29, 1813-1863 (doi:10.1007/s00332-019-09531-w)). More specifically, we are interested in large deformation analysis of bodies that undergo a continuous and simultaneous accretion and ablation on their boundaries while under external loads. In this formulation, the natural configuration of an accreting-ablating body is a time-dependent Riemannian [Formula: see text]-manifold with a metric that is an unknown a priori and is determined after solving the accretion-ablation initial-boundary-value problem. In addition to the time of attachment map, we introduce a time of detachment map that along with the time of attachment map, and the accretion and ablation velocities, describes the time-dependent reference configuration of the body. The kinematics, material manifold, material metric, constitutive equations and the balance laws are discussed in detail. As a concrete example and application of the geometric theory, we analyse a thick hollow circular cylinder made of an arbitrary incompressible isotropic material that is under a finite time-dependent extension while undergoing continuous ablation on its inner cylinder boundary and accretion on its outer cylinder boundary. The state of deformation and stress during the accretion-ablation process, and the residual stretch and stress after the completion of the accretion-ablation process, are computed. This article is part of the theme issue 'Foundational issues, analysis and geometry in continuum mechanics'.

Buckling of Thin-Walled Cylinders from Three Dimensional Nonlinear Elasticity.

The famous bifurcation analysis performed by Flügge on compressed thin-walled cylinders is based on a series of simplifying assumptions, which allow to obtain the bifurcation landscape, together with explicit expressions for limit behaviours: surface instability, wrinkling, and Euler rod buckling. The most severe assumption introduced by Flügge is the use of an incremental constitutive equation, which does not follow from any nonlinear hyperelastic constitutive law. This is a strong limitation for the applicability of the theory, which becomes questionable when is utilized for a material characterized by a different constitutive equation, such as for instance a Mooney-Rivlin material. We re-derive the entire Flügge's formulation, thus obtaining a framework where any constitutive equation fits. The use of two different nonlinear hyperelastic constitutive equations, referred to compressible materials, leads to incremental equations, which reduce to those derived by Flügge under suitable simplifications. His results are confirmed, together with all the limit equations, now rigorously obtained, and his theory is extended. This extension of the theory of buckling of thin shells allows for computationally efficient determination of bifurcation landscapes for nonlinear constitutive laws, which may for instance be used to model biomechanics of arteries, or soft pneumatic robot arms.

A viscoelastic constitutive model for human femoropopliteal arteries.

High failure rates present challenges for surgical and interventional therapies for peripheral artery disease of the femoropopliteal artery (FPA). The FPA's demanding biomechanical environment necessitates complex interactions with repair devices and materials. While a comprehensive understanding of the FPA's mechanical characteristics could improve medical treatments, the viscoelastic properties of these muscular arteries remain poorly understood, and the constitutive model describing their time-dependent behavior is absent. We introduce a new viscoelastic constitutive model for the human FPA grounded in its microstructural composition. The model is capable of detailing the contributions of each intramural component to the overall viscoelastic response. Our model was developed utilizing fractional viscoelasticity and tested using biaxial experimental data with hysteresis and relaxation collected from 10 healthy human subjects aged 57 to 65 and further optimized for high throughput and automation. The model accurately described the experimental data, capturing significant nonlinearity and hysteresis that were particularly pronounced circumferentially, and tracked the contribution of passive smooth muscle cells to viscoelasticity that was twice that of the collagen fibers. The high-throughput parameter estimation procedure we developed included a specialized objective function and modifications to enhance convergence for the common exponential-type fiber laws, facilitating computational implementation. Our new model delineates the time-dependent behavior of human FPAs, which will improve the fidelity of computational simulations investigating device-artery interactions and contribute to their greater physical accuracy. Moreover, it serves as a useful tool to investigate the contribution of arterial constituents to overall tissue viscoelasticity, thereby expanding our knowledge of arterial mechanophysiology. STATEMENT OF SIGNIFICANCE: The demanding biomechanical environment of the femoropopliteal artery (FPA) necessitates complex interactions with repair devices and materials, but the viscoelastic properties of these muscular arteries remain poorly understood with the constitutive model describing their time-dependent behavior being absent. We hereby introduce the first viscoelastic constitutive model for the human FPA grounded in its microstructures. This model was tested using biaxial mechanical data collected from 10 healthy human subjects between the ages of 57 to 65. It can detail the contributions of each intramural component to the overall viscoelastic response, showing that the contribution of passive smooth muscle cells to viscoelasticity is twice that of collagen fibers. The usefulness of this model as tool to better understand arterial mechanophysiology was demonstrated.

Local response and emerging nonlinear elastic length scale in biopolymer matrices.

Nonlinear stiffening is a ubiquitous property of major types of biopolymers that make up the extracellular matrices (ECM) including collagen, fibrin, and basement membrane. Within the ECM, many types of cells such as fibroblasts and cancer cells have a spindle-like shape that acts like two equal and opposite force monopoles, which anisotropically stretch their surroundings and locally stiffen the matrix. Here, we first use optical tweezers to study the nonlinear force-displacement response to localized monopole forces. We then propose an effective-probe scaling argument that a local point force application can induce a stiffened region in the matrix, which can be characterized by a nonlinear length scale R* that increases with the increasing force magnitude; the local nonlinear force-displacement response is a result of the nonlinear growth of this effective probe that linearly deforms an increasing portion of the surrounding matrix. Furthermore, we show that this emerging nonlinear length scale R* can be observed around living cells and can be perturbed by varying matrix concentration or inhibiting cell contractility.

Strain energy density as a Gaussian process and its utilization in stochastic finite element analysis: application to planar soft tissues.

Data-based approaches are promising alternatives to the traditional analytical constitutive models for solid mechanics. Herein, we propose a Gaussian process (GP) based constitutive modeling framework, specifically focusing on planar, hyperelastic and incompressible soft tissues. The strain energy density of soft tissues is modeled as a GP, which can be regressed to experimental stress-strain data obtained from biaxial experiments. Moreover, the GP model can be weakly constrained to be convex. A key advantage of a GP-based model is that, in addition to the mean value, it provides a probability density (i.e. associated uncertainty) for the strain energy density. To simulate the effect of this uncertainty, a non-intrusive stochastic finite element analysis (SFEA) framework is proposed. The proposed framework is verified against an artificial dataset based on the Gasser-Ogden-Holzapfel model and applied to a real experimental dataset of a porcine aortic valve leaflet tissue. Results show that the proposed framework can be trained with limited experimental data and fits the data better than several existing models. The SFEA framework provides a straightforward way of using the experimental data and quantifying the resulting uncertainty in simulation-based predictions.

Recent Advances in Tissue-Engineered Cardiac Scaffolds-The Progress and Gap in Mimicking Native Myocardium Mechanical Behaviors.

Heart failure is the leading cause of death in the US and worldwide. Despite modern therapy, challenges remain to rescue the damaged organ that contains cells with a very low proliferation rate after birth. Developments in tissue engineering and regeneration offer new tools to investigate the pathology of cardiac diseases and develop therapeutic strategies for heart failure patients. Tissue -engineered cardiac scaffolds should be designed to provide structural, biochemical, mechanical, and/or electrical properties similar to native myocardium tissues. This review primarily focuses on the mechanical behaviors of cardiac scaffolds and their significance in cardiac research. Specifically, we summarize the recent development of synthetic (including hydrogel) scaffolds that have achieved various types of mechanical behavior-nonlinear elasticity, anisotropy, and viscoelasticity-all of which are characteristic of the myocardium and heart valves. For each type of mechanical behavior, we review the current fabrication methods to enable the biomimetic mechanical behavior, the advantages and limitations of the existing scaffolds, and how the mechanical environment affects biological responses and/or treatment outcomes for cardiac diseases. Lastly, we discuss the remaining challenges in this field and suggestions for future directions to improve our understanding of mechanical control over cardiac function and inspire better regenerative therapies for myocardial restoration.

Mechanics of tensegrity cell units incorporating asymmetry and insights into mollitaxis.

The mechanical response of a contractile cell anchored to the substrate through focal adhesions is studied by means of an asymmetric pre-strained tensegrity structure obeying a neo-Hookean stress-strain law. The aim is to assess the influence of overall asymmetric contraction on the cell durotaxis and on the growth of the focal adhesion plaque. The asymmetric kinematics of the system is obtained in two ways, that is by assuming a gradient of the substrate stiffness and through asymmetric buckling. Equivalent springs are purposely considered to represent the stiffness of the ensemble formed by the substrate, the focal adhesion plaque and the integrin ligands. Then, contraction results from elastic strains induced by competing polymerization and actomyosin contraction. The cell mechanical response in terms of durotaxis and its coupling with focal adhesion plaque growth is finally analysed with respect to the effects of asymmetry, gaining some insights into how this asymmetry could participate to redirect cell migration, both in terms of durotaxis and mollitaxis.

Pre-strains and buckling in mechanosensitivity of contractile cells and focal adhesions: A tensegrity model.

We demonstrate that several key aspects of the contractile activity of a cell interacting with the substrate can be captured by means of a non linear elastic tensegrity mechanical system made of a tensile element in parallel with a buckling-prone component, and exchanging forces with the surroundings through an extracellular matrix-focal adhesion complex. Mechanosensitivity of the focal adhesion plaque is triggered by pre-strain-driven buckling of the system induced either by pre-contraction or pre-polymerization of the constituents. The impact of pre-polymerization on the mechanical force and the implications of using linear and nonlinear elasticity for the focal adhesion plaque are assessed.

Exponents of the one-term Ogden model: insights from simple shear.

Isotropic one-term Ogden models are widely used to predict the mechanical response of both incompressible elastomers and soft tissue. Even though the exponent might be chosen to yield excellent agreement with some aspects of mechanical response, there is no guarantee that these models will be physically realistic in all situations. We show here that, in particular, the predictions of models with either negative or large positive exponents do not seem physically realistic in simple shear. The mechanical response of materials in shear should be physically realistic to ensure rational and reliable predictions for complex geometries and boundary conditions. We suggest that for problematic values of exponents of one-term models that extra Ogden invariants should necessarily be included in the model. This article is part of the theme issue 'The Ogden model of rubber mechanics: Fifty years of impact on nonlinear elasticity'.

Linear, weakly nonlinear and fully nonlinear models for soft tissues: which ones provide the most reliable estimations of the stiffness?

Benign and malignant lesions in tissues or organs can be detected by elastographic investigations in which pathological regions are spotted from local alterations of the stiffness. As is known, the shear modulus provides a measure of the stiffness of an elastic material. Based on the classical theory of linear elasticity, an elastogram yields estimations of the linear shear modulus from measurements of the speed of small-amplitude transverse waves propagating in the medium tested. In this paper, we show that the estimation of the shear modulus can be improved significantly by employing the fourth-order weakly nonlinear theory of elasticity (FOE), and indicate how the stiffness can be assessed more precisely with the use of FOE. We discuss also why FOE provides more reliable results than the fully nonlinear theory of elasticity. This article is part of the theme issue 'The Ogden model of rubber mechanics: Fifty years of impact on nonlinear elasticity'.

Coupling solid and fluid stresses with brain tumour growth and white matter tract deformations in a neuroimaging-informed model.

Brain tumours are among the deadliest types of cancer, since they display a strong ability to invade the surrounding tissues and an extensive resistance to common therapeutic treatments. It is therefore important to reproduce the heterogeneity of brain microstructure through mathematical and computational models, that can provide powerful instruments to investigate cancer progression. However, only a few models include a proper mechanical and constitutive description of brain tissue, which instead may be relevant to predict the progression of the pathology and to analyse the reorganization of healthy tissues occurring during tumour growth and, possibly, after surgical resection. Motivated by the need to enrich the description of brain cancer growth through mechanics, in this paper we present a mathematical multiphase model that explicitly includes brain hyperelasticity. We find that our mechanical description allows to evaluate the impact of the growing tumour mass on the surrounding healthy tissue, quantifying the displacements, deformations, and stresses induced by its proliferation. At the same time, the knowledge of the mechanical variables may be used to model the stress-induced inhibition of growth, as well as to properly modify the preferential directions of white matter tracts as a consequence of deformations caused by the tumour. Finally, the simulations of our model are implemented in a personalized framework, which allows to incorporate the realistic brain geometry, the patient-specific diffusion and permeability tensors reconstructed from imaging data and to modify them as a consequence of the mechanical deformation due to cancer growth.

Nonlinear Elasticity Assessment with Optical Coherence Elastography for High-Selectivity Differentiation of Breast Cancer Tissues.

Soft biological tissues, breast cancer tissues in particular, often manifest pronounced nonlinear elasticity, i.e., strong dependence of their Young's modulus on the applied stress. We showed that compression optical coherence elastography (C-OCE) is a promising tool enabling the evaluation of nonlinear properties in addition to the conventionally discussed Young's modulus in order to improve diagnostic accuracy of elastographic examination of tumorous tissues. The aim of this study was to reveal and quantify variations in stiffness for various breast tissue components depending on the applied pressure. We discussed nonlinear elastic properties of different breast cancer samples excised from 50 patients during breast-conserving surgery. Significant differences were found among various subtypes of tumorous and nontumorous breast tissues in terms of the initial Young's modulus (estimated for stress < 1 kPa) and the nonlinearity parameter determining the rate of stiffness increase with increasing stress. However, Young's modulus alone or the nonlinearity parameter alone may be insufficient to differentiate some malignant breast tissue subtypes from benign. For instance, benign fibrous stroma and fibrous stroma with isolated individual cancer cells or small agglomerates of cancer cells do not yet exhibit significant difference in the Young's modulus. Nevertheless, they can be clearly singled out by their nonlinearity parameter, which is the main novelty of the proposed OCE-based discrimination of various breast tissue subtypes. This ability of OCE is very important for finding a clean resection boundary. Overall, morphological segmentation of OCE images accounting for both linear and nonlinear elastic parameters strongly enhances the correspondence with the histological slices and radically improves the diagnostic possibilities of C-OCE for a reliable clinical outcome.

Actomyosin contractility and buckling of microtubules in nucleation, growth and disassembling of focal adhesions.

Building up and maintenance of cytoskeletal structure in living cells are force-dependent processes involving a dynamic chain of polymerization and depolymerization events, which are also at the basis of cells' remodelling and locomotion. All these phenomena develop by establishing cell-matrix interfaces made of protein complexes, known as focal adhesions, which govern mechanosensing and mechanotransduction mechanisms mediated by stress transmission between cell interior and external environment. Within this framework, by starting from a work by Cao et al. (Biophys J 109:1807-1817, 2015), we here investigate the role played by actomyosin contractility of stress fibres in nucleation, growth and disassembling of focal adhesions. In particular, we propose a tensegrity model of an adherent cell incorporating nonlinear elasticity and unstable behaviours, which provides a new kinematical interpretation of cellular contractile forces and describes how stress fibres, microtubules and adhesion plaques interact mechanobiologically. The results confirm some experimental evidences and suggest how the actomyosin contraction level could be exploited by cells to actively control their adhesion, eventually triggering cytoskeleton reconfigurations and migration processes observed in both physiological conditions and diseases.

Nanofibrous tissue engineering scaffold with nonlinear elasticity created by controlled curvature and porosity.

Micro-crimped fibers have been widely used in the field of tissue repair to mimic the natural tissue structure and mechanical properties. However, the electrospun nanofibrous membrane is a kind of dense structure, which cannot meet the requirements of mechanical properties and permeability. In this study, we prepared nanofibrous scaffold with controllable porosity and crimpness by sacrificing fiber components and releasing residual stress. The results show that the crimpness of the fiber is positively related to the porosity, and with the increase of porosity, the fiber crimpness increases greatly. Meanwhile, the scaffold modulus was reduced by 86% and the elongation at break doubled, which is similar to natural blood vessels. Moreover, it is found that the porous micro-crimped fiber scaffold promotes the adhesion and diffusion of endothelial cells, and facilitates the rapid endothelialization of the scaffold, which has a great potential for practical application.

A Nonlinear Elastic Model for Compressible Aluminum Alloys with Finite Element Implementation.

In this paper, a three-dimensional model of nonlinear elastic material is proposed. The model is formulated in the framework of Green elasticity, which is based on the specific elastic energy potential. Equivalently, this model can be associated to the deformation theory of plasticity. The constitutive relationship, derived from the assumed specific energy, divides the material's behavior into two stages: the first one starts with an initial almost linear stress-strain relation which, for higher strain, smoothly turns into the second stage of hardening. The proposed relation mimics the experimentally observed response of ductile metals, aluminum alloys in particular. In contrast to the classic deformation theory of plasticity or the plastic flow theory, the presented model can describe metal compressibility in both stages of behavior. The constitutive relationship is non-reversible expressing stress as a function of strain. Special attention is given to the calibration process, in which a one-dimensional analog of the three-dimensional model is used. Various options of calibration based on uniaxial stress test are extensively discussed. A finite element code is written and verified in order to validate the model. Solutions of selected problems, obtained via ABAQUS, confirm the correctness of the model and its usefulness in numerical simulations, especially for buckling.

Structure-Elastic Properties Relationships in Gelling Carrageenans.

Gelling carrageenans are polysaccharides extracted from the Gigartinales order of red algae. These are additives used essentially in the food industry for texturizing, stabilizing or gelling various formulations. Although a consensual gel mechanism has been reached which encompasses a coil-to-helix transition followed by the self-assembling of helices in a network, the structure-elastic relationships in the network are still to be clearly established. This paper reviews the reports in which carrageenan gel structures have been systematically compared with gel elastic properties. The focus is on the sizes documented for structural units, such as strands, aggregates, voids or network meshes, as well as on the reported linear and nonlinear elastic characteristics. The insufficient rationalization of carrageenan gel elasticity by models which take on board mechanically relevant structural features is underlined. After introducing selected linear and nonlinear elastic models, preliminary results comparing such models to structural and rheological data are presented. In particular, the concentration scaling of the strain hardening exhibited by two types of carrageenan gels is discussed.