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The modeling of the viability decay of viruses in sessile droplets is addressed considering a droplet sitting on a smooth surface characterized by a specific contact angle. To investigate, at prescribed temperature, how surface energy of the material and ambient humidity cooperate to determine the virus viability, we propose a model which involves the minimum number of thermodynamically relevant parameters. In particular, by considering a saline water droplet (one salt) as the simplest approximation of real solutions (medium and natural/artificial saliva), the evaporation is described by a first-order time-dependent nonlinear differential equation properly rearranged to obtain the contact angle evolution as the sole unknown function. The analyses were performed for several contact angles and two typical droplet sizes of interest in real situations by assuming constant ambient temperature and relative humidity in the range 0–100%. The results of the simulations, given in terms of time evolution of salt concentration, vapor pressure, and droplet volume, elucidate some previously not yet well-understood dynamics, demonstrating how three main regimes—directly implicated in nontrivial trends of virus viability and to date only highlighted experimentally—can be recognized as the function of relative humidity. By recalling the concept of cumulative dose of salts (CD), to account for the effect of the exposition of viruses to salt concentration on virus viability, we show how the proposed approach could suggest a chart of a virus fate by predicting its survival time at a given temperature as a function of the relative humidity and contact angle. We found a good agreement with experimental data for various enveloped viruses and predicted in particular for the Phi6 virus, a surrogate of coronavirus, the characteristic U-shaped dependence of viability on relative humidity. Given the generality of the model and once experimental data are available that link the vulnerability of a certain virus, such as SARS-CoV-2, to the concentrations of salts or other substances in terms of CD, it is felt that this approach could be employed for antivirus strategies and protocols for the prediction/reduction of human health risks associated with SARS-CoV-2 and other viruses.

Wrinkling has recently attracted an increasing interest by suggesting a number of unforeseeable applications in many emerging material science and engineering fields. If guided and somehow designed, wrinkles could be in fact used as an alternative printing way for realizing complex surface geometries and thus employed as an innovative bottom-up process in the fabrication of nano- and micro-devices. For these reasons, the prediction of wrinkles of films adhering on flat as well as on structured substrata is a challenging task, genesis and development of the phenomenon being not yet completely understood both when thin membranes are coupled with soft supports and in cases where the geometry of the surfaces are characterized by complex three-dimensional profiles. Here we investigate the experimental formation of new intriguing and somehow unforeseeable wrinkled patterns achieved on periodic structures, by showing prediction through a new hybrid analytical-numerical strategy capable to overcome some common obstacles encountered in modeling film wrinkling on flat and 3D-shaped substrata. The proposed approach, which drastically reduces the computational effort, furnishes a helpful way for predicting both qualitative and quantitative results in terms of wrinkling patterns, magnitude and wavelength, by also allowing to follow the onset of film instabilities and the progressive evolution of the phenomenon until its final stage. Keywords: Thin film, Wrinkling, PDMS substrates, Lithium niobate crystals, FEM simulations

Total Hip Arthroplasty has been one of the most successful surgical procedure in terms of patient outcomes and satisfaction. However, due to increase in life expectancy and the related incidence of age-dependent bone diseases, a growing number of cases of intra-operative fractures lead to revision surgery with high rates of morbidity and mortality. Surgeons choose the type of the implant, either cemented or cementless prosthesis, on the basis of the age, the quality of the bone and the general medical conditions of the patients. Generally, no quantitative measures are available to assess the intra-operative fracture risk. Consequently, the decision-making process is mainly based on surgical operators’ expertise and qualitative information obtained from imaging. Motivated by this scenario, we here propose a mechanical-supported strategy to assist surgeons in their decisions, by giving intelligible maps of the risk fracture which take into account the interplay between the actual mechanical strength distribution inside the bone tissue and its response to the forces exerted by the implant. In the presented study, we produce charts and patient-specific synthetic “traffic-light” indicators of fracture risk, by making use of ad hoc analytical solutions to predict the stress levels in the bone by means of Computed Tomography-based mechanical and geometrical parameters of the patient. We felt that if implemented in a friendly software or proposed as an app, the strategy could constitute a practical tool to help the medical decision-making process, in particular with respect to the choice of adopting cemented or cementless implant.

In this paper, the recently proposed structural optimization strategy, the Galilei-Optimization (GO), is adapted for improving the toughness response of a holed two-dimensional lattice system made of a network of micro-beams whose geometrical arrangement was prescribed. By taking advantage of the possibility of minimizing stress gradients and stress peaks around the hole via GO, we redesigned the cross sections of the lattice beam elements, equalizing the stresses over the entire domain. Consequently, the resulting optimized microstructure highlighted a significant enhancement of the overall toughness due to a drastic decrease of the stress concentration factor in the hole proximity, preserving the initial stiffness and lowering the total overall weight. To validate the robustness of the procedure and the numerical Finite Element outcomes, two non-optimized and optimized structures were actually built up through 3D printing and tested in the laboratory under the same boundary conditions used for the simulations. This evidence confirmed the effectiveness of the proposed method in obtaining optimized beam-like plates with high toughness, which could pave the way for designing new light materials with extreme mechanical performance well beyond the sole stiffness and strength.

Recently, non-local configurations have been proposed by adding beyond nearest neighbour couplings among elements in lattices to obtain roton-like dispersion relations and phase and group velocities with opposite signs. Even though the introduction of non-local elastic links in metamaterials has unlocked unprecedented possibilities, literature models and prototypes seem neither to provide criteria to compare local and non-local lattices nor to discuss any related rules governing the transition between the two configurations. A physically reasonable principle that monoatomic one-dimensional chains must obey to pass from single- to multi-connected systems is here proposed through a mass conservation law for elastic springs thereby introducing a suitable real dimensionless parameter [Formula: see text] to tune stiffness distribution. Therefore, the dispersion relations as a function of [Formula: see text] and of the degree of non-locality [Formula: see text] are derived analytically, demonstrating that the proposed principle can be rather interpreted as a general mechanical consistency condition to preserve proper dynamics, involving the spring-to-bead mass ratio. Finally, after discussing qualitative results and deriving some useful inequalities, numerical simulations and two-dimensional FFTs are performed for some paradigmatic examples to highlight key dynamics features exhibited by chains with finite length as the parameters [Formula: see text] and [Formula: see text] vary.This article is part of the theme issue 'Current developments in elastic and acoustic metamaterials science (Part 2)'.

Cell membranes, mediator of many biological mechanisms from adhesion and metabolism up to mutation and infection, are highly dynamic and heterogeneous environments exhibiting a strong coupling between biochemical events and structural re-organisation. This involves conformational changes induced, at lower scales, by lipid order transitions and by the micro-mechanical interplay of lipids with transmembrane proteins and molecular diffusion. Particular attention is focused on lipid rafts, ordered lipid microdomains rich of signalling proteins, that co-localise to enhance substance trafficking and activate different intracellular biochemical pathways. In this framework, the theoretical modelling of the dynamic clustering of lipid rafts implies a full multiphysics coupling between the kinetics of phase changes and the mechanical work performed by transmembrane proteins on lipids, involving the bilayer elasticity. This mechanism produces complex interspecific dynamics in which membrane stresses and chemical potentials do compete by determining different morphological arrangements, alteration in diffusive walkways and coalescence phenomena, with a consequent influence on both signalling potential and intracellular processes. Therefore, after identifying the leading chemo-mechanical interactions, the present work investigates from a modelling perspective the spatio-temporal evolution of raft domains to theoretically explain co-localisation and synergy between proteins' activation and raft formation, by coupling diffusive and mechanical phenomena to observe different morphological patterns and clustering of ordered lipids. This could help to gain new insights into the remodelling of cell membranes and could potentially suggest mechanically based strategies to control their selectivity, by orienting intracellular functions and mechanotransduction., (© 2023. The Author(s).)

In this work, starting from an approach previously proposed by the Authors, we put forward an extension to the large deformation regime of the dimensionally-reduced formulation for peridynamic thin plates, including both hyperelasticity and fracture. In particular, the model, validated against numerical simulations, addresses the problem of the peeling in nonlocal thin films, which when attached to a soft substrate highlights how nonlocality of the peeled-off layer might greatly influence the whole structural response and induce some unforeseen mechanical behaviours that could be useful for engineering applications. Through a key benchmark example, we in fact demonstrate that de-localization of damage and less destructive failure modes take place, these effects suggesting the possibility of ad hoc  conceiving specific networks of nonlocal interactions between material particles, corresponding to lattice-equivalent structure of the nonlocal model treated, of interest in designing new material systems and interfaces with enhanced toughness and adhesive properties., Competing Interests: Conflict of interestThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© The Author(s) 2024.)

Equilibrium bifurcation in natural systems can sometimes be explained as a route to stress shielding for preventing failure. Although compressive buckling has been known for a long time, its less-intuitive tensile counterpart was only recently discovered and yet never identified in living structures or organisms. Through the analysis of an unprecedented all-in-one paradigm of elastic instability, it is theoretically and experimentally shown that coexistence of two curvatures in human finger joints is the result of an optimal design by nature that exploits both compressive and tensile buckling for inducing luxation in case of traumas, so realizing a unique mechanism for protecting tissues and preventing more severe damage under extreme loads. Our findings might pave the way to conceive complex architectured and bio-inspired materials, as well as next generation artificial joint prostheses and robotic arms for bio-engineering and healthcare applications.

We study the equilibrium configurations related to the growth of an elastic fibre in a confining flexible ring. This system represents a paradigm for a variety of biological, medical, and engineering problems. We consider a simplified geometry in which initially the container is a circular ring of radius R . Quasi-static growth is then studied by solving the equilibrium equations as the fibre length l increases, starting from l = 2 R . Considering both the fibre and the ring as inextensible and unshearable, we find that beyond a critical length, which depends on the relative bending stiffness, the fibre buckles. Furthermore, as the fibre grows further it folds, distorting the ring until it induces a break in mirror symmetry at l > 2π R . We get that the equilibrium shapes depend only on two dimensionless parameters: the length ratio μ = l / R and the bending stiffnesses ratio κ . These findings are also supported by finite element simulation. Finally we experimentally validate the theoretical results showing a very good quantitative prediction of the observed buckling and folding regimes at variable geometrical parameters.

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., (© 2022. The Author(s).)

Bone is an extraordinary biological material that continuously adapts its hierarchical microstructure to respond to static and dynamic loads for offering optimal mechanical features, in terms of stiffness and toughness, across different scales, from the sub-microscopic constituents within osteons-where the cyclic activity of osteoblasts, osteoclasts, and osteocytes redesigns shape and percentage of mineral crystals and collagen fibers-up to the macroscopic level, with growth and remodeling processes that modify the architecture of both compact and porous bone districts. Despite the intrinsic complexity of the bone mechanobiology, involving coupling phenomena of micro-damage, nutrients supply driven by fluid flowing throughout hierarchical networks, and cells turnover, successful models and numerical algorithms have been presented in the literature to predict, at the macroscale, how bone remodels under mechanical stimuli, a fundamental issue in many medical applications such as optimization of femur prostheses and diagnosis of the risk fracture. Within this framework, one of the most classical strategies employed in the studies is the so-called Stanford's law, which allows uploading the effect of the time-dependent load-induced stress stimulus into a biomechanical model to guess the bone structure evolution. In the present work, we generalize this approach by introducing the bone poroelasticity, thus incorporating in the model the role of the fluid content that, by driving nutrients and contributing to the removal of wastes of bone tissue cells, synergistically interacts with the classical stress fields to change homeostasis states, local saturation conditions, and reorients the bone density rate, in this way affecting growth and remodeling. Through two paradigmatic example applications, i.e. a cylindrical slice with internal prescribed displacements idealizing a tract of femoral diaphysis pushed out by the pressure exerted by a femur prosthesis and a bone element in a form of a bent beam, it is highlighted that the present model is capable to catch more realistically both the transition between spongy and cortical regions and the expected non-symmetrical evolution of bone tissue density in the medium-long term, unpredictable with the standard approach. A real study case of a femur is also considered at the end in order to show the effectiveness of the proposed remodeling algorithm., (© 2022. The Author(s).)

Grounded in the interdisciplinary crosstalk among physics and biological sciences, precision medicine-based diagnosis and treatment strategies have recently gained great attention for the actual applicability of new engineered approaches in many medical fields, particularly in oncology. Within this framework, the use of ultrasounds employed to attack cancer cells in tumors to induce possible mechanical damage at different scales has received growing attention from scholars and scientists worldwide. With these considerations in mind, on the basis of ad hoc elastodynamic solutions and numerical simulations, we propose a pilot study for in silico modeling of the propagation of ultrasound waves inside tissues, with the aim of selecting proper frequencies and powers to be irradiated locally through a new teragnostic platform based on Lab-on-Fiber technology, baptized as a hospital in the needle and already the object of a patent. It is felt that the outcomes and the related biophysical insights gained from the analyses could pave the way for envisaging new integrated diagnostic and therapeutic approaches that might play a central role in future applications of precise medicine, starting from the growing synergy among physics, engineering and biology., (© 2022. The Author(s).)

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., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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 AFM ∈M AFM ≠C FM ∈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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 Elsevier Ltd. All rights reserved.)

Background: The aim of the study was to compare the bone mineral density changes between unmatched patients undergoing total hip arthroplasty receiving uncemented and cemented type of implants. Previous studies have used DEXA or a two dimensional analysis to estimate the bone quality following total joint replacement, whereas this study presents the changes in three dimensions., Methods: Fifty subjects both male and females receiving both cemented and uncemented type of implant were recruited. Two CT scans were taken of each subject, the first at 24 h post surgery and the second one 1 year after surgery. The scans were calibrated using a phantom converting the Hounsfield units to bone mineral density values in g/cm 3 . The two scans were registered together using anatomical landmarks and resliced to compare the two femurs in the identical frame of reference. The bone density gain and loss was calculated by comparing density values between the two sets of scans., Findings: The results showed that most of the bone loss was located around the Lesser Trochanter and some bone density gain at the distal tip of the implant. The three dimensional density changes occur differently between individuals and the study showed no correlation of bone loss with age., Interpretation: The bone loss occurred mostly at the proximal femur, which is in agreement with previously presented studies. By carrying out three dimensional analysis on the bone gain and loss on the femur, it is possible to identify the patients that are showing high degree of bone loss., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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.

Adhesive attachment systems consisting of multiple tapes or strands are commonly found in nature, for example in spider web anchorages or in mussel byssal threads, and their structure has been found to be ingeniously architected in order to optimize mechanical properties: in particular, to maximize dissipated energy before full detachment. These properties emerge from the complex interplay between mechanical and geometric parameters, including tape stiffness, adhesive energy, attached and detached lengths and peeling angles, which determine the occurrence of three main mechanisms: elastic deformation, interface delamination and tape fracture. In this paper, we introduce a formalism to evaluate the mechanical performance of multiple tape attachments in different parameter ranges, where an optimal (not maximal) adhesion energy emerges. We also introduce a numerical model to simulate the multiple peeling behaviour of complex structures, illustrating its predictions in the case of the staple-pin architecture. Finally, we present a proof-of-principle experiment to illustrate the predicted behaviour. We expect the presented formalism and the numerical model to provide important tools for the design of bioinspired adhesive systems with tuneable or optimized detachment properties.

Ischemic mitral regurgitation (IMR) occurs as an adverse consequence of left ventricle remodeling post-myocardial infarction. A change in mitral valve configuration with an imbalance between closing and tethering forces underlie this pathological condition. These abnormalities lead to impaired leaflet coaptation and a variable degree of mitral regurgitation, which can in turn influence the ventricular filling status, the heart rhythm and the afterload regardless of the residual ischemic insult. The IMR correction can be pursued through under-sizing mitral annuloplasty and papillary muscle approximation to restore the mitral valve and left ventricle physiological geometry to, consequently, achieve normalization of the engaged physical forces. Because the structures involved undergo extremely large deformations, a biomechanics model based on the Euler's Elastica -the mitral leaflet- interlaced with nonlinear chordae tendineae anchored on papillary muscles has been constructed to elucidate the interactions between closing and tethering forces. The model takes into account the actual updated geometrical and mechanical features of the valvular and subvalvular apparatuses in physiological and IMR conditions, as well as in case of papillary muscle approximation, finally furnishing ad hoc geometry-based mathematical relations that could be utilised to support-and optimize-the relevant choices in cardiac surgery.

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., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Total hip arthroplasty is a ubiquitously successful orthopedic surgical procedure, whose prevalence is rising worldwide. While many investigations focus on characterizing periprosthetic pathophysiology, the objective of our research is to develop and describe multi-metric assemblies as a first step toward creating a patient-specific mobility index that rehabilitators and orthopedic surgeons can utilize for prescribing their respective procedures. In total, 48 total hip arthroplasty patients (both cemented and uncemented) undergoing unilateral, primary surgery went through computed tomographic scans and gait analysis measurements both before and 1 year following their surgery. Altogether, the reported quantitative metrics include 11 spatial and temporal gait parameters, muscle density, and electromyography signals from the rectus femoris, vastus lateralis, and vastus medialis, and bone mineral density values from bioimage analysis around the implant stem. We found that measured parameters from a subgroup were sensitive to changes observed during patient recovery, implicating the predictive sensitivity of these patient conditions. Most post-operative gait parameters changed significantly, while electromyography data indicated few significant differences. Moreover, results from bioimage analyses indicate a general reduction of periprosthetic bone mineral density after 1 year, in association with increasing density of the quadriceps muscles. Furthermore, this work identifies which quantitative metrics undergo the greatest variation after total hip arthroplasty and demonstrates the clinical feasibility of a multimodal approach to mobility assessment that may ultimately support decision-making for post-surgical rehabilitation protocols.

Total Hip Arthroplasty requires pre-surgical evaluation between un-cemented and cemented prostheses. A Patient with intra-operative periprosthetic fracture and another with a successful outcome were recruited, and their finite element models were constructed by processing CT data, assuming elastic-plastic behavior of the bone as function of the local density. To resemble the insertion of the prosthesis into the femur, a fictitious thermal dilatation is applied to the broach volume. Strain-based fracture risk factor is estimated, depicting results in terms of the total mechanical strain expressed using a simple "traffic lights" color code to provide immediate, concise, and intelligible pre-operative information to surgeons.

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.

The development of techniques able to characterize and map the pressure field is crucial for the widespread use of acoustofluidic devices in biotechnology and lab-on-a-chip platforms. In fact, acoustofluidic devices are powerful tools for driving precise manipulation of microparticles and cells in microfluidics in non-contact modality. Here, we report a full and accurate characterization of the movement of particles subjected to acoustophoresis in a microfluidic environment by holographic imaging. The particle displacement along the direction of the ultrasound wave propagation, coinciding with the optical axis, is observed and investigated. Two resonance frequencies are explored, varying for each the amplitude of the applied signal. The trajectories of individual tracers, accomplished by holographic measurements, are fitted with the theoretical model thus allowing the retrieval of the acoustic energy densities and pressure amplitudes through full holographic analysis. The absence of prior calibration, being independent of the object shape and the possibility of implementing automatic analysis make the use of holography very appealing for applications in devices for biotechnologies.

The integration of digital holography (DH) imaging and the acoustic manipulation of micro-particles in a microfluidic environment is investigated. The ability of DH to provide efficient 3D tracking of particles inside a microfluidic channel is exploited to measure the position of multiple objects moving under the effect of stationary ultrasound pressure fields. The axial displacement provides a direct verification of the numerically computed positions of the standing wave's node, while the particles' transversal movement highlights the presence of nodes in the planar direction. Moreover, DH is used to follow the aggregation dynamics of trapped spheres in such nodes by using aggregation rate metrics.

Ischemic mitral regurgitation (IMR) is a form of mitral insufficiency that is characterized by papillary muscle (PM) displacement, leaflet tethering, reduced closing forces, and different degree of annular dilatation. Treatment of this condition includes mitral valve replacement or mitral valve repair with restrictive annuloplasty. Recent evidences in mitral valve repair showed that addressing only the annulus and neglecting the subvalvular apparatus provides a suboptimal operation with poor long-term results. However, the complexity of the geometrical aberrances occurring in IMR demands for more accurate analysis also involving the biomechanics underlying the failing mitral valve and subvalvular apparatus. Finite element analysis (FEA) is a powerful tool in this context and we developed a biomechanical model of mitral valve and subvalvular unit using 3D geometry of the leaflets, annulus, chordae and PM. After the application of structural properties of materials to these elements and simulation of systemic pressure loading, FEA could be used to directly determine biomechanical changes and geometry variations. We believe this approach can provide valuable information to better address the surgical treatment of IMR and answer some of the questions still pending in IMR management., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

The failure of mitral valve repair procedures revealed in the outcomes of the recent randomized studies is suggesting the necessity for a better understanding of the biomechanical mechanisms underlying the failure of the surgical approaches. Use of biomechanical modelling and finite element analysis (FEA) in cardiovascular research is an important aid in this context. In our group we developed a biomechanical model taking into account all the component of the mitral valve functional unit including the valve leaflets, the annulus, the papillary muscles, the chordae tendinea and the ventricular geometry. The two-dimensional mathematical model was capable to predict some of the actual geometrical and mechanical features of the valvular and subvalvular apparatuses in physiological and pathological conditions providing the engineering quantitative relations between closing and tethering forces and the mechanisms governing the mitral valve unit function. This model might further become patient-specific by means of 3D reconstruction of clinical imaging. Images are first converted in a standard vector format (DICOM, etc.), then automatically translated in a "structural" finite element model and finally implemented in a finite element code. This allows for in silico simulations to virtually explore the effects of different surgical approaches at an early stage after the procedure, to help the operative decision processes, or to optimize the design of surgical implants., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Objective: The symmetry of mitral valve tethering and regional left ventricle wall dysfunction are reported to play a fundamental role in the outcomes and long-term durability of surgical repair in ischemic mitral regurgitation (IMR). We recently demonstrated in a randomized clinical trial (the Papillary Muscle Approximation trial) the superiority of papillary muscle approximation (PMA) in combination with standard restrictive annuloplasty (RA) in severe IMR over annuloplasty alone in terms of adverse left ventricular remodeling and mitral regurgitation (MR) recurrence. This approach, however, failed to produce a survival advantage and was still plagued by a high incidence of reoperation. We therefore performed a subanalysis of the PMA trial on the basis of preoperative parameters to elucidate the value of subvalvular surgery in certain subcategories of patients with the aim of creating a decisional algorithm on the best operative strategy., Methods: We performed a subanalysis of PMA trial, evaluating 96 patients with severe IMR and eligible for myocardial revascularization randomized to PMA + RA (n = 48) versus RA alone (n = 48) in association with coronary artery bypass grafting. Endpoints included left ventricular remodeling, MR recurrence, overall mortality, reoperation, and a composite cardiac endpoint (cardiac death, stroke, reintervention, hospitalization for heart failure, or New York Heart Association class worsening). Stratification variables were preoperative symmetry of mitral valve tethering and regional wall motion abnormality., Results: PMA improved ventricular remodeling and recurrence of MR in both preoperative symmetric and asymmetric tethering and in case of inferior wall dyskinesia but did not produce an additional benefit in anterolateral wall dysfunction., Conclusions: Preoperative symmetric and asymmetric tethering and isolated inferior wall dyskinesia are an indication for subvalvular apparatus surgery in IMR., (Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

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., (© 2016 Wiley Periodicals, Inc.)

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., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

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.

Background: In patients with ischemic mitral regurgitation, leaflet prolapse requires an accurate evaluation since surgical approach depends on valvular and subvalvular characteristics. This study aims to describe a cohort of patients over a long-term follow up, analyzing survival, reoperation and predictive factors of surgical outcomes., Methods and Results: From March 1994 to June 2011, 75 patients with ischemic mitral regurgitation and leaflet prolapse underwent surgical myocardial revascularization and mitral valve repair (90.7%) or replacement (9.3%). Our cohort was followed up until April 2015, with a mean follow up of 7 ± 3 years. Cardiac-related deaths occurred in 26 patients, with a mean survival of 114.2 months, including eight patients with in-hospital mortality. Reoperation was performed in 14 patients, due to valve repair failure. Twenty-six patients experienced moderate-to-severe mitral regurgitation. A preoperative LVEDD > 62 mm, LVESD > 52 mm, previous anteroseptal myocardial infarction, diffuse coronary artery disease, papillary anatomy type 1, partial rupture of the papillary muscle, A1-A2 scallop prolapse and postoperative mitral valve configuration (tenting area, tenting height, alfa-1 angle and alfa-2 angle) were identified as independent predictors of poor outcome. An index quantifying the stress on the annulus imparted by annuloplasty was elaborated and predicted endpoints., Conclusion: Leaflet prolapse is an important entity in patients with ischemic mitral regurgitation, and its pathogenic mechanism mostly relies on papillary muscle lesion or elongation. Perioperative parameters describing geometric features of left ventricle, valvular and subvalvular components should be considered to provide a tailored approach for mitral valve repair, or to opt for immediate replacement in case of unfavorable geometry., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Computed tomography (CT) provides both anatomical and density information about tissues. Bone is segmented by raw images and Finite Element Method (FEM) voxel-based meshing technique is achieved by matching each CT voxel to a single finite element (FE). As a consequence of the automated model reconstruction, unstable elements - i.e. elements insufficiently anchored to the whole model and thus potentially involved in partial rigid body motion - can be generated, a crucial problem in obtaining consistent FE models, hindering mechanical analyses. Through the classification of instabilities on topological connections between elements, a numerical procedure is proposed in order to avoid unconstrained models.