Search

Abstract Poromechanics plays a key role in modelling hard and soft tissue behaviours, by providing a thermodynamic framework in which chemo-mechanical mutual interactions among fluid and solid constituents can be consistently rooted, at different scale levels. In this context, how different biological species (including cells, extra-cellular components and chemical metabolites) interplay within complex environments is studied for characterizing the mechanobiology of tumor growth, governed by intratumoral residual stresses that initiate mechanotransductive processes deregulating normal tissue homeostasis and leading to tissue remodelling. Despite the coupling between tumor poroelasticity and interspecific competitive dynamics has recently highlighted how microscopic cells and environment interactions influence growth-associated stresses and tumor pathophysiology, the nonlinear interlacing among biochemical factors and mechanics somehow hindered the possibility of gaining qualitative insights into cells dynamics. Motivated by this, in the present work we recover the linear poroelasticity in order to benefit of a reduced complexity, so first deriving the well-known Lyapunov stability criterion from the thermodynamic dissipation principle and then analysing the stability of the mechanical competition among cells fighting for common space and resources during cancer growth and invasion. At the end, the linear poroelastic model enriched by interspecific dynamics is also exploited to show how growth anisotropy can alter the stress field in spherical tumor masses, by thus indirectly affecting cell mechano-sensing. GraphicAbstract

Langmuir monolayers at gas/liquid interfaces provide a rich framework to investigate the interplay between multiscale geometry and mechanics. Monolayer collapse is investigated at a topological and geometric level by building a scale space M from experimental imaging data. We present a general lipid monolayer collapse phase diagram, which shows that wrinkling, folding, crumpling, shear banding, and vesiculation are a continuous set of mechanical states that can be approached by either tuning monolayer composition or temperature. The origin of the different mechanical states can be understood by investigating the monolayer geometry at two scales: fluorescent vs atomic force microscopy imaging. We show that an interesting switch in continuity occurs in passing between the two scales, C

The mechanical performance of reinforced composites is strongly influenced at different scales by the stress transferred at the matrix-fibre interfaces and at any surface where material discontinuity occurs. In particular, the mechanical response of elastomeric composites where the reinforcement is composed by cords with helically wound fibres is heavily compromised by fatigue and delamination phenomena occurring at cord-rubber as well as at the ply interfaces, since rubber and polymeric matrices are mainly vulnerable to the accumulation of deviatoric energy due to the shear stresses transferred across the surfaces. Despite the large diffusion of composites in a vast field of applications and the mature knowledge of their behaviour, some key mechanical aspects underlying failure mechanisms are still partially unclear. For example, stress amplification and strain localization are often difficult to predict by means of analytical solutions and averaging techniques that usually conceal stress gradients. In this work, we analyse coupling between torsional and tensile loads in twisted cords, which are adopted in many cases to reinforce composites and rubbers in tire applications. We provide a model characterized by an enriched cord-matrix mechanical interplay able to theoretically explain and predict actual stress distributions responsible for the onset of delamination and fatigue-guided phenomena that are experimentally observed in these composites. In particular, we demonstrate that the assumption of a monoclinic/trigonal behaviour for the mechanical response of the hierarchical strands allows to estimate, by means of analytical formulas and a homogenization approach, hitherto neglected shear stresses at the matrix-reinforcement interface. These stresses are transferred to the neighbouring regions, leading to post-elastic behaviour and failure events. Finite Element simulation results for rubber/cord composites under various boundary conditions highlight the discrepancies in mechanical behaviour between the proposed model and standard approaches in the literature, while experimental tests performed on composite rubber pads confirm theoretical predictions, providing qualitative evidence of the onset of cracks.

Growing biological media develop residual stresses to make compatible elastic and inelastic growth-induced deformations, which in turn remodel the tissue properties modifying the actual elastic moduli and transforming an initially isotropic and homogeneous material into a spatially inhomogeneous and anisotropic one. This process is crucial in solid tumor growth mechanobiology, the residual stresses directly influencing tumor aggressiveness, nutrients walkway, necrosis and angiogenesis. With this in mind, we here analyze the problem of a hyperelastic sphere undergoing finite heterogeneous growth, in cases of different boundary conditions and spherical symmetry. By following an analytical approach, we obtain the explicit expression of the tangent elasticity tensor at any point of the material body as a function of the prescribed growth, by involving a small-on-large procedure and exploiting exact solutions for layered media. The results allowed to gain several new insights into how growth-guided mechanical stresses and remodeling processes can influence the solid tumor development. In particular, we highlight that— under hypotheses consistent with mechanical and physiological conditions—auxetic (negative Poisson ratio) transformations of the elastic response of selected growing mass districts could occur and contribute to explain some not yet completely understood phenomena associated to solid tumors. The general approach proposed in the present work could be also helpfully employed to conceive composite materials where ad hoc pre-stress distributions can be designed to obtain auxetic or other selected mechanical properties.

Langmuir monolayers at gas/liquid interfaces provide a rich framework to investigate the interplay between multiscale geometry and mechanics. Monolayer collapse is investigated at a topological and geometric level by building a scale space M from experimental imaging data. We present a general lipid monolayer collapse phase diagram, which shows that wrinkling, folding, crumpling, shear banding, and vesiculation are a continuous set of mechanical states that can be approached by either tuning monolayer composition or temperature. The origin of the different mechanical states can be understood by investigating the monolayer geometry at two scales: fluorescent vs atomic force microscopy imaging. We show that an interesting switch in continuity occurs in passing between the two scales, C A F M ∈ M A F M ≠ C F M ∈ M . Studying the difference between monolayers that fold vs shear band, we show that shear banding is correlated to the persistence of a multi-length scale microstructure within the monolayer at all surface pressures. A detailed analytical geometric formalism to describe this microstructure is developed using the theory of structured deformations. Lastly, we provide the first ever finite element simulation of lipid monolayer collapse utilizing a direct mapping from the experimental image space M into a simulation domain P . We show that elastic dissipation in the form of bielasticity is a necessary and sufficient condition to capture loss of in-plane stability and shear banding.

Composites are experiencing a new era. The spatial resolution at which is to date possible to build up complex architectured microstructures through additive manufacturing-based and sintering of powder metals 3D printing techniques, as well as the recent improvements in both filament winding and automated fiber deposition processes, are opening new unforeseeable scenarios for applying optimization strategies to the design of high-performance structures and metamaterials that could previously be only theoretically conceived. Motivated by these new possibilities, the present work, by combining computational methods, analytical approaches and experimental analysis, shows how finite element Design Optimization algorithms can be ad hoc rewritten by identifying as design variables the orientation of the reinforcing fibers in each ply of a layered structure for redesigning fiber-reinforced composites exhibiting at the same time high stiffness and toughening, two features generally in competition each other. To highlight the flexibility and the effectiveness of the proposed strategy, after a brief recalling of the essential theoretical remarks and the implemented procedure, selected example applications are finally illustrated on laminated plates under different boundary conditions, cylindrical layered shells with varying curvature subjected to point loads and composite tubes made of carbon fiber-reinforced polymers, recently employed as structural components in advanced aerospace engineering applications.

The progressive falling of barriers among disciplines is opening unforeseen scenarios in diagnosis and treatment of cancer diseases. By sharing models and mature knowledge in physics, engineering, computer sciences and molecular biology, synergistic efforts have in fact contributed in the last years to re-think still unsolved problems, shedding light on key roles of mechanobiology in tumors and envisaging new effective strategies for a precise medicine. The use of ultrasounds for altering cancer cells’ program is one of the most attracting grounds to be explored in oncophysics, although how to administer mechanical energy to impair selected cell structures and functions simultaneously overcoming the critical trade-off between the impact of the cure and the patient risk still remains an open issue. Within this framework, by starting from the theoretical possibility of selectively attacking malignant cells by exploiting the stiffness discrepancies between tumor and healthy single cells, first proposed by Fraldi et al. (2015), we here investigate the in-frequency response of an overall spherical close-packing of geometrically equal polyhedral cells to gain insights into how mechanical resonance and vibration-induced failure phenomena can be oriented to destroy specific target units when both the cell populations coexist, as it happens for in vivo cases. Inspired by the dynamic action of earthquakes – which fracture only selected elements among adjacent ones in the same structure or damage individual constructions in contiguous buildings – we study the harmonic response of hierarchically architectured cell agglomerates, inhabited by both tumor and healthy cells that interact mutually throughout the extra-cellular matrix and whose cytoskeleton is modeled as a nonlinear soft-tensegrity structure. Numerical Finite Element results show that, at frequencies compatible with low intensity therapeutic ultrasounds, mechanical resonance and possible fatigue cycles of the pre-stressed actin filaments and microtubules can be selectively induced in cancer cells as a function of the global volume fraction of the cell species, paving the way for future engineered treatment protocols.

The stability of equilibrium is a fundamental topic in mechanics and applied sciences. Apart from its central role in most engineering fields, it also arises in many natural systems at any scale, from folding/unfolding processes of macromolecules and growth-induced wrinkling in biological tissues to meteorology and celestial mechanics. As such, a few key models represent essential benchmarks in order to gain significant insights into more complex physical phenomena. Among these models, a cornerstone is represented by a structure made of two straight axially deformable bars, connected by an elastic hinge and simply supported at the ends, which are capable of buckling under a compressive axial force. This classical example has been proposed and analysed in some depth by Feodosyev but the attention is here focused on an apparently paradoxical result given by this model, i.e. the existence of a lower bound for the axial-to-flexural stiffness ratio in order for the bifurcation to take place. This enigma is solved theoretically by showing that, differently from other classical stability problems, constitutive and geometric nonlinearities cannot be a priori disconnected and an ideal linearized axial constitutive law cannot be employed in this case. The theory is validated with an experiment, and post-buckling and energy extrema of the proposed solution are discussed as well, highlighting possible snap-back and snap-through phenomena. Finally, the results are extended to the complementary case of tensile buckling.

Adherent cells are able to actively generate internal forces, channelled by cytoskeletal protein filaments and transmitted through transmembrane receptors to the surrounding environment by means of focal adhesions. Cells also dynamically interact with extracellular matrix by sensing external chemo-mechanical stimuli and then inducing formation of stress fibres mediated by polymerization/de-polymerization processes which continuously redesign the interplay between structural organization and contractility activities in the cytoskeleton, so orchestrating selected signal pathways at the basis of many important cell’s physiological functions like adhesion, migration and division. Despite chemo- and duro-taxis have been intensively studied in the last years to understand how cells move on a substrate, their polarization and reorientation – observed during gastrulation, wound healing and morphogenesis – are only partially understood. By starting from the evidence highlighted in some recent studies that cells reorient in response to substrata deformation by essentially obeying a pure mechanical interaction, we propose to interpret the seeming overall cells’ rotation resulting from the reconfiguration of their cytoskeleton – here named mechanotropism – as a nonlinear optimization problem in which the adherent cell aims to align along directions leading it to minimize a physically coherent measure of work spent to deform the elastic substrate while retaining a prescribed level of homeostatic contractile force. To do this, the single-cell is simply modelled as a finite size contractile force dipole that acts on the boundary of a half-space perturbed by applied point loads. The effects of fences of forces acting orthogonally and tangentially on the boundary of the adhesion medium and encircling the cell are then investigated, so obtaining solutions that predict multiple non-trivial cell polarizations as functions of number, direction, relative magnitude and distance from the cell-dipole of the forces, as well as of the substrate’s Poisson ratio, with unprecedented outcomes under the hypothesis of auxetic (i.e. negative Poisson ratio) materials. The results lead to envisage that the proposed theoretical model might contribute to unveil the mechanobiological principles ruling in vivo cells orientation processes by guiding the design of novel experimental strategies and to conceive new mechanics-based markers for guessing cells’ pathological conditions from their mechanotropism.

Complex mechanical behaviours are generally met in macroscopically homogeneous media as effects of inelastic responses or as results of unconventional material properties, which are postulated or due to structural systems at the meso/micro-scale. Examples are strain localization due to plasticity or damage and metamaterials exhibiting negative Poisson’s ratios resulting from special porous, eventually buckling, sub-structures. In this work, through ad hoc conceived mechanical paradigms, we show that several non-standard behaviours can be obtained simultaneously by accounting for kinematical discontinuities, without invoking inelastic laws or initial voids. By allowing mutual sliding among rigid tesserae connected by pre-stressed hyperelastic links, we find several unusual kinematics such as localized shear modes and tensile buckling-induced instabilities, leading to deck-of-cards deformations—uncapturable with classical continuum models—and unprecedented ‘bulky’ auxeticity emerging from a densely packed, geometrically symmetrical ensemble of discrete units that deform in a chiral way. Finally, after providing some analytical solutions and inequalities of mechanical interest, we pass to the limit of an infinite number of tesserae of infinitesimal size, thus transiting from discrete to continuum, without the need to introduce characteristic lengths. In the light of the theory of structured deformations, this result demonstrates that the proposed architectured material is nothing else than the first biaxial paradigm of structured continuum —a body that projects, at the macroscopic scale, geometrical changes and disarrangements occurring at the level of its sub-macroscopic elements.

Extreme adhesion mechanisms are shown in a wide number of situations in nature, from structures of single cells and spider web anchorages to hierarchical organization of ends and pads of insects and reptiles. With this in mind, we here propose a general formulation of multiple peeling theory accounting for geometrical and constitutive nonlinearities, i.e. large deformations and hyperelasticity. Pre-stress of adherent tracts and different initial V-shaped configurations of the tapes have been also included in the modelling. By following an analytical approach, closed-form solutions and explicit formulas were given for predicting pull-off critical forces and optimality conditions maximizing the adhesion strength, as well as for tracing the evolution of the delamination process, from the detaching onset to its progressive behaviour. Kendall and previous constitutively linear multiple peeling theory approaches were all recovered as limit cases, gaining insights into the role played by nonlinearities and pre-stress and also demonstrating – with mathematically rigorous arguments – the asymptotic character of the detaching phenomenon observed experimentally. Example applications and simple key tests were provided to show the effectiveness of the approach, which could help to interpret peeling in nature and to design materials with enhanced adhesive properties.

The evolution of species is governed by complex phenomena in which biological and environmental features may interact dynamically. Subterranean mammals dig tunnels whose diameter minimizes energetic costs during excavations and display anatomical adaptations in order to burrow structurally stable tunnels according to specific features of the soil. These animals weight from less than 50 g up to 1–2 kg, and dig tunnels with diameters from 3 to 15 cm. The use of allometric laws has enabled these data to be correlated. However, since tunnels need to be stable with respect to the geomechanical characteristics of the resident soils, a mathematical treatment linking the admissible dimensions of tunnels to the environment here suggests a mechanically grounded correlation between the body mass of subterranean mammals and the maximum dimensions of tunnels. Remarkably, such theoretical findings reflect very well the empirical allometric relationship and contribute to explain the wide differences observed in body sizes of subterranean mammals. In this respect, a far from ancillary role of environmental mechanics on the morphological evolution of subterranean mammals can be hypothesized.

In the last years, due to their exceptional mechanical properties (elastic modulus of about 1 TPa and tensile strength of 130–150 GPa), single and multi-wall carbon nanotubes (CNTs and MWCNTs) have encountered an increasing interest among scientists. More recently, a number of studies have also envisaged the possibility of building up a new generation of composites with elastomeric or polymeric matrix, reinforced with MWCNTs, to gain high mechanical performances and other physical properties. However, independently from problems related to accuracy and costs associated to the processing and the production of MWCNTS and some difficulties in exactly controlling their dimensions, distribution and geometry, a detailed micromechanical description of the overall elastic response of these complex structures—that appear to be constituted by several layers organized as hollow cylindrical phases wrapped around a central core—is still at the center of a vivid debate, because it is expected that their chirality induces an anisotropic (e.g. trigonal/monoclinic) elastic behavior, which is characterized by a coupling between torsion and axial deformations. This is a relevant aspect for the developing of stresses inside the reinforcements and, importantly, for predicting the actual stress regimes at the interfaces and in turn the overall mechanical behavior of these composites, with transferring of spurious shear stresses and size effects. In this framework, due to the difficulties of deriving analytical results for the mechanical response of these multi-wall elastically monoclinic cylinders, the vast majority of the literature efforts have presented numerical results, for example by performing Finite Element (FE) analyses or by estimating the stiffness of these structures, at different scale levels, through molecular dynamics (MD) strategies. The present contribution is therefore aimed to furnish new closed-form elastic solutions for general compound cylinders, made by n hallow monoclinic/trigonal phases and a possible central core, under prescribed boundary conditions of interest for applications, to be implemented in computational FE algorithms for faithfully replicating the actual mechanical response of composites reinforced with MWCNTs.

Clustering of ligand-binding receptors of different types on thickened isles of the cell membrane, namely lipid rafts, is an experimentally observed phenomenon. Although its influence on cell's response is deeply investigated, the role of the coupling between mechanical processes and multiphysics involving the active receptors and the surrounding lipid membrane during ligand-binding has not yet been understood. Specifically, the focus of this work is on G-protein-coupled receptors (GPCRs), the widest group of transmembrane proteins in animals, which regulate specific cell processes through chemical signalling pathways involving a synergistic balance between the cyclic Adenosine Monophosphate (cAMP) produced by active GPCRs in the intracellular environment and its efflux, mediated by the Multidrug Resistance Proteins (MRPs) transporters. This paper develops a multiphysics approach based on the interplay among energetics, multiscale geometrical changes and mass balance of species, i.e. active GPCRs and MRPs, including diffusion and kinetics of binding and unbinding. Because the obtained energy depends upon both the kinematics and the changes of species densities, balance of mass and of linear momentum are coupled and govern the space-time evolution of the cell membrane. The mechanobiology involving remodelling and change of lipid ordering of the cell membrane allows to predict dynamics of transporters and active receptors -in full agreement with experimentally observed cAMP levels- and how the latter trigger rafts formation and cluster on such sites. Within the current scientific debate on Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) and on the basis of the ascertained fact that lipid rafts often serve as an entry port for viruses, it is felt that approaches accounting for strong coupling among mechanobiological aspects could even turn helpful in better understanding membrane-mediated phenomena such as COVID-19 virus-cell interaction.

Mechanical stress accumulating during growth in solid tumors plays a crucial role in the tumor mechanobiology. Stresses arise as a consequence of the spatially inhomogeneous tissue growth due to the different activity of healthy and cancer cells inhabiting the various districts of the tissue, an additional piling up effect, induced by stress transferring across the scales, contributing to determine the total stress occurring at the macroscopic level. The spatially inhomogeneous growth rates accompany nonuniform and time-propagating stress profiles, which constitute mechanical barriers to nutrient transport and influence the intratumoral interstitial flow, in this way deciding the starved/feeded regions, with direct aftereffects on necrosis, angiogenesis, cancer aggressiveness and overall tumor mass size. Despite their ascertained role in tumor mechanobiology, stresses cannot be directly appraised neither from overall tumor size nor through standard non-invasive measurements. To date, the sole way for qualitatively revealing their presence within solid tumors is ex vivo, by engraving the excised masses and then observing opening between the cut edges. Therefore, to contribute to unveil stresses and their implications in tumors, it is first proposed a multiscale model where Volterra-Lotka (predator/prey-like) equations describing the interspecific (environment-mediated) competitions among healthy and cancer cells are coupled with equations of nonlinear poroelasticity. Then, an experimental study on mice injected subcutaneously with a suspension of two different cancer cell lines (MiaPaCa-2 and MDA.MB231) was conducted to provide experimental evidences that gave qualitative and some new quantitative confirmations of the theoretical model predictions.

OBJECTIVES Reinforcements for the pulmonary autograft (PA) in the Ross operation have been introduced to avoid the drawback of conduit expansion and failure. With the aid of an in silico simulation, the biomechanical boundaries applied to a healthy PA during the operation were studied to tailor the best implant technique to prevent reoperation. METHODS Follow-up echocardiograms of 66 Ross procedures were reviewed. Changes in the dimensions and geometry of reinforced and non-reinforced PAs were evaluated. Miniroot and subcoronary implantation techniques were used in this series. Mechanical stress tests were performed on 36 human pulmonary and aortic roots explanted from donor hearts. Finite element analysis was applied to obtain high-fidelity simulation under static and dynamic conditions of the biomechanical properties and applied stresses on the PA root and leaflet and the similar components of the native aorta. RESULTS The non-reinforced group showed increases in the percentages of the mean diameter that were significantly higher than those in the reinforced group at the level of the Valsalva sinuses (3.9%) and the annulus (12.1%). The mechanical simulation confirmed geometrical and dimensional changes detected by clinical imaging and demonstrated the non-linear biomechanical behaviour of the PA anastomosed to the aorta, a stiffer behaviour of the aortic root in relation to the PA and similar qualitative and quantitative behaviours of leaflets of the 2 tissues. The annulus was the most significant constraint to dilation and affected the distribution of stress and strain within the entire complex, with particular strain on the sutured regions. The PA was able to evenly absorb mechanical stresses but was less adaptable to circumferential stresses, potentially explaining its known dilatation tendency over time. CONCLUSIONS The absence of reinforcement leads to a more marked increase in the diameter of the PA. Preservation of the native geometry of the PA root is crucial; the miniroot technique with external reinforcement is the most suitable strategy in this context.

Tensegrity structures are special architectures made by floating compressed struts kept together by a continuous system of tensioned cables. Their existence in a mechanically stable form is decided by the possibility of finding geometrical configurations such that pre-stressed tendons and bars can ensure self-equilibrium of the forces transmitted through the elastic network, the overall stiffness of which finally depends on both the rigidity of the compressed elements and the cables’ pre-stress. The multiplicity of shapes that tensegrity structures can assume and their intrinsic capability to be deployable and assembled, so storing (and releasing) elastic energy, have motivated their success as paradigm –pioneeringly proposed three decades ago by the intuition of Donald E. Ingber– to explain some underlying mechanisms regulating dynamics of living cells. The interlaced structure of the cell cytoskeleton, constituted by actin microfilaments, intermediate filaments and microtubules which continuously change their spatial organization and pre-stresses through polymerization/depolymerization processes, seems in fact to steer migration, adhesion and cell division by obeying the tensegrity construct. Even though rough calculations lead to estimate discrepancies of less than one order of magnitude when comparing axial stiffness of actin filaments (cables) and microtubules (struts) and recent works have shown bent microtubules among stretched filaments, no one has yet tried to remove the standard hypothesis of rigid struts in tensegrity structures when used to idealize the cell cytoskeleton mechanical response. With reference to the 30-element tensegrity cell paradigm, we thus introduce both compressibility and bendability of the struts and accordingly rewrite the theory to simultaneously take into account geometrical non-linearity (i.e. large deformations) and hyper-elasticity of both tendons and bars, so abandoning the classical linear stress-strain constitutive assumptions. By relaxing the hypothesis of rigidity of the struts, we demonstrate that some quantitative confirmations and many related extreme and somehow counter-intuitive mechanical behaviors actually exploited by cells for storing/releasing energy, resisting to applied loads and deforming by modulating their overall elasticity and shape through pre-stress changes and instability-guided configurational switching, can be all theoretically found. It is felt that the proposed new soft-strut tensegrity model could pave the way for a wider use of engineering models in cell mechanobiology and in designing bio-inspired materials and soft robots.

The pulmonary artery autograft (PA) is the ideal substitute for aortic valve disease in children and young adult. However, it is harnessed by the issue of long-term dilation and regurgitation, often requiring surgery. PA implanted in aortic position during the growth phase in children undergoes a process of mechanical remodeling. We previously developed a semiresorbable armored prosthesis able to mechanically sustain the neoaorta preventing dilation and to gradually integrate with the PA wall inducing a progressive arterial-like tissue positive remodeling. We also described the mechanisms of growth, remodeling and stress shielding of the reinforced PA through a mathematical model. We sought to demonstrate the biological counterpart and the potential molecular mechanisms underlying this histological and mechanical remodeling. A specific mathematical model was developed to describe mechanical behavior of the PA. Mallory trichrome red staining and immunohistochemistry for MMP-9 were performed to elucidate extracellular matrix remodeling phenomena. Apoptosis and cell proliferation were determined by TUNEL assay and immunohistochemistry for Ki67, respectively. An histological remodeling phenomenon sustained by increased level of MMP-9, augmented cell proliferation and reduced apoptosis in the reinforced PA was demonstrated. The mathematical model predicted the biomechanical behavior subtended by the histological changes of the PA in these settings. Changes in metalloproteinases (MMP-9), cell proliferation and apoptosis are the main actors in the remodeling process occurring after transposition of the PA into systemic regimens. Use of semiresorbable reinforcements might induce a positive remodeling of the PA in the context of Ross operation. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2785-2793, 2016.

Growth of biological tissues has been recently treated within the framework of Continuum Mechanics, by adopting heterogeneous poroelastic models where the interaction between soft matrix and interstitial fluid flow is coupled with inelastic effects ad hoc introduced to simulate the macroscopic volumetric growth determined by cells division, cells growth and extracellular matrix changes occurring at the micro-scale level. These continuum models seem to overcome some limitations intrinsically associated to other alternative approaches based on mass balances in multiphase systems, because the crucial role played by residual stresses accompanying growth and nutrients walkway is preserved. Nevertheless, when these strategies are applied to analyze solid tumors, mass growth is usually assigned in a prescribed form that essentially copies the in vitro measured intrinsic growth rates of the cell species. As a consequence, some important cell-cell dynamics governing mass evolution and invasion rates of cancer cells, as well as their coupling with feedback mechanisms associated to in situ stresses, are inevitably lost and thus the spatial distribution and the evolution with time of the growth inside the tumor –which would be results rather than inputs– are forced to enter in the model simply as data. In order to solve this paradox, it is here proposed an enhanced multi-scale poroelastic model undergoing large deformations and embodying inelastic growth, where the net growth terms directly result from the “interspecific” predator-prey (Volterra/Lotka-like) competition occurring at the micro-scale level between healthy and abnormal cell species. In this way, a system of fully-coupled non-linear PDEs is derived to describe how the fight among cell species to grab the available common resources, stress field, pressure gradients, interstitial fluid flows driving nutrients and inhomogeneous growth all simultaneously interact to decide the tumor fate.

Tensegrity systems occur when self-equilibrated states are achieved through the interplay of pretensed (cables) and precompressed (struts) elements. The principles that govern these types of structures have been widely observed in many living systems across the scales and recently recognized, with soft or buckling bars, in the cytoskeleton as well as within single protein architectures as associated with key cellular and subcellular processes. To properly model these mechanical phenomena, some limitations dictated by the mostly linear approaches –used in literature when dealing with tensegrity structures – needto be overcome. To this aim, the present work provides a novel 2-element soft-tensegrity paradigm that includes, for the first time, (neo-Hookean) finite hyperelasticity for cable and strut, the latter potentially undergoing both contraction and buckling at each prestressed equilibrium stage. It is finally shown that constitutive properties, instability and bar deformability cooperate to determine unusual form-finding results, providing peculiar overall mechanical responses as external forces are applied.

In recent years, experimental evidences have suggested important direct implications of viscoelasticity of human cells and cell cytoskeleton dynamics on some relevant collective and single-cell behaviors such as migration, adhesion, and morphogenesis. Consequently, the mechanical properties of single cells and how cells respond to mechanical stimuli have been at the center of a vivid debate in the scientific community. By referencing important experimental findings from the literature that have shown that human metastatic tumor cells are approximately 70% softer than benign cells, independently from the cell lines examined, the present authors have very recently theoretically demonstrated that these differences in stiffness might be exploited to mechanically discriminate healthy and cancer cells, for example, through low-intensity therapeutic ultrasound. In particular, by using a generalized viscoelastic paradigm combining classical and fractional derivative-based models, it has been found that selected frequencies (from tens to hundreds of kilohertz) are associated with resonancelike phenomena that are prevailing on thermal fluctuations and hence could be, at least in principle, helpfully utilized for both targeting and selectively attacking tumor cells. With the aim of investigating the effect of the prestress (for instance, induced in protein filaments during cell adhesion) on the overall cell stiffness and, in turn, on its in-frequency response, a simple multiscale scheme is proposed in this paper to bottom-up enrich the spring-pot-based viscoelastic single-cell models by incorporating finite elasticity and thereby determining through sensitivity analyses the role played by the stretched state of the cytoskeletal elements on the cell vibration.

Mechanical characterization and modeling of elastomers under different load conditions have attracted the interest of the scientific community in the last 50 years; despite the wide literature and the related scientific and industrial activity in this field, many different phenomena are to date not yet well understood. In order to fill in some of these gaps, a hybrid approach has been here used by integrating the use of forefront techniques like the Digital Image Correlation with mechanical testing machines able to perform non-standard biaxial tests in static and dynamic loading conditions. In a first part of the work, some components of a planar biaxial testing device (BiaxTester, developed by Coesfeld GmbH.) able to perform mechanical testing on elastomeric materials have been partially redesigned, in order to optimize reliability of the results obtained in terms of stress-strain curves. As shown, control of the boundary conditions through adequate optimization of the clamping system and of the specimen shape may lead in fact to more homogeneous strain fields, thus excluding, or at least reducing, edge effects such as shear strains or compressive phenomena around the clamps. Successively, the aforementioned system optimization led to investigate the arise of different phenomena connected to the Mullins effect in filled elastomers, which emerge as a consequence of the complex network interactions among the elastomeric matrix and the rigid reinforcement particles, finally resulting in a combination of stress softening, permanent set, hysteresis and induced anisotropy. The BiaxTester, together with the instruments of Digital Image Correlation and proper mechanical modeling strategies, have all shown to be invaluable instruments to control the actual stress and strain fields in complex loading conditions, so allowing to gain crucial information and new insights for predicting with high accuracy static and dynamic mechanical behaviors of elastomers.

The pulmonary artery autograft (PA) is the ideal substitute for aortic valve disease in children and young adult. However, it is harnessed by the issue of long-term dilation and regurgitation, often requiring surgery. PA implanted in aortic position during the growth phase in children undergoes a process of mechanical remodeling. We previously developed a semiresorbable armored prosthesis able to mechanically sustain the neoaorta preventing dilation and to gradually integrate with the PA wall inducing a progressive arterial-like tissue positive remodeling. We also described the mechanisms of growth, remodeling and stress shielding of the reinforced PA through a mathematical model. We sought to demonstrate the biological counterpart and the potential molecular mechanisms underlying this histological and mechanical remodeling. A specific mathematical model was developed to describe mechanical behavior of the PA. Mallory trichrome red staining and immunohistochemistry for MMP-9 were performed to elucidate extracellular matrix remodeling phenomena. Apoptosis and cell proliferation were determined by TUNEL assay and immunohistochemistry for Ki67, respectively. An histological remodeling phenomenon sustained by increased level of MMP-9, augmented cell proliferation and reduced apoptosis in the reinforced PA was demonstrated. The mathematical model predicted the biomechanical behavior subtended by the histological changes of the PA in these settings. Changes in metalloproteinases (MMP-9), cell proliferation and apoptosis are the main actors in the remodeling process occurring after transposition of the PA into systemic regimens. Use of semiresorbable reinforcements might induce a positive remodeling of the PA in the context of Ross operation. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2785-2793, 2016.

Synthetic grafts are often satisfactory employed in cardiac and vascular surgery, including expanded poly(ethylene terephthalate) or expanded poly(tetrafluoroethylene). However, accumulating evidences suggest the emergence of worrisome issues concerning the long-term fate of prosthetic grafts as large vessel replacement. Disadvantages related to the use of synthetic grafts can be traced in their inability of mimicking the elasto-mechanical characteristics of the native vascular tissue, local suture overstress leading to several prosthesis-related complications and retrograde deleterious effects on valve competence, cardiac function and perfusion. Motivated by this, in the present work it is analyzed - by means of both elemental biomechanical paradigms and more accurate in silico Finite Element simulations - the physical interaction among aorta, autograft and widely adopted synthetic (Dacron) prostheses utilized in transposition of pulmonary artery, highlighting the crucial role played by somehow unexpected stress fields kindled in the vessel walls and around suture regions, which could be traced as prodromal to the triggering of anomalous remodelling processes and alterations of needed surgical outcomes. Theoretical results are finally compared with histological and surgical data related to a significant experimental animal campaign conducted by performing pulmonary artery transpositions in 30 two-month old growing lambs, followed up during growth for six months. The in vivo observations demonstrate the effectiveness of the proposed biomechanical hypothesis and open the way for possible engineering-guided strategies to support and optimize surgical procedures.

Breast Capsular Contracture (BCC) is one of the adverse complications occurring with greater incidence in breast augmentation surgical procedures. Its formation can be interpreted as the conclusive result of the physiological process known as response to a foreign body. From a biochemical standpoint, the formation of the peri-prosthetic capsule is certainly a multifactorial process: many hypotheses concerning its etiology have been suggested in the literature and a number of related pharmacological protocols have been consequently proposed to clinically treat this pathology with the aim to prevent further complications and avoid future re-interventions. However, the vast majority of these theories seems to be only partially supported by clinical outcomes and thus a shared opinion on this matter is still absent among specialists. Within this framework, by starting from clinical observations which highlighted an unexpected correlation between histo-morphological features of fibrotic capsules and overall size of breast implants, the present study investigates the hypothesis that the biomechanical interaction between prosthesis and host tissue may play a crucial role in the biological processes governing the pathological phenomenon at hand. Therefore, to shed light on the underlying mechanisms which could trigger the breast capsular contracture, both simple analytical solutions, in which elasticity and growth are simultaneously taken into account, and more accurate geometrically faithful Finite Element-based numerical simulations have been exploited. The theoretical findings demonstrate that somehow counter-intuitive radial and hoop stress fields occur at the capsula-implant interface in a way such that their combined action, independently from other possible concurrent factors, results significantly amplified for small-size breast prostheses, localized stress peaks in these cases promoting detaching and rippling phenomena actually observed in BCC clinical complications.

Ross operation, i.e., the use of autologous pulmonary artery to replace diseased aortic valve, has been recently at the center of a vivid debate regarding its unjust underuse in the surgical practice. Keystone of the procedure regards the use of an autologous biologically available graft which would preserve the anticoagulative and tissue homeostatic functions normally exerted by the native leaflets and would harmoniously integrate in the vascular system, allowing for progressive somatic growth of aortic structures. With this respect, recently, some of the authors have successfully pioneered a large animal model of transposition of pulmonary artery in systemic pressure load in order to reproduce the clinical scenario in which this procedure might be applied and allow for the development and testing of different devices or techniques to improve the pulmonary autograft (PA) performance, by testing a bioresorbable mesh for PA reinforcement. In the present work, to support and supplement the in vivo animal experimentation, a mathematical model is developed in order to simulate the biomechanical changes in pulmonary artery subjected to systemic pressure load and reinforced with a combination of resorbable and auxetic synthetic materials. The positive biological effects on vessel wall remodeling, the regional somatic growth phenomena and prevention of dilatative degeneration have been analyzed. The theoretical outcomes show that a virtuous biomechanical cooperation between biological and synthetic materials takes place, stress-shielding guiding the physiological arterialization of vessel walls, consequently determining the overall success of the autograft system.