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In this work, we characterize the impact of large-volume processing upon the analytical sensitivity of flow-through paper-based immunoassays. Larger sample volumes feature greater molar quantities of available analyte, but the assay design principles which would enable the rapid collection of this dilute target are ill-defined. We developed a finite-element model to explore the operating conditions under which processing large sample volumes via pressure-driven convective flow would yield an improved binding signal. Our simulation results underscore the importance of establishing a high local concentration of the analyte-binding species within the porous substrate. This elevated abundance serves to enhance the binding kinetics, matching the time scale of target capture to the period during which the sample is in contact with the test zone (i.e., the effective residence time). These findings were experimentally validated using the rcSso7d-cellulose-binding domain (CBD) fusion construct, a bifunctional binding protein which adsorbs to cellulose in high abundance. As predicted by our modeling efforts, the local concentration achieved using the rcSso7d-CBD species is uniquely enabling for sensitivity enhancement through large-volume processing. The rapid analyte depletion which occurs at this high surface density also permits the processing of large sample volumes within practical time scales and flow regimes. Using these findings, we present guidance for the optimal means of processing large sample volumes for enhanced assay sensitivity.

Damage detection and localization in civil engineering constructions using dynamic analysis has become an important topic in recent years. This paper presents a methodology based on non-destructive detection, localization and quantification of multiple damages in simple and continuous beams, and a more complex structure, namely two-dimensional frame structure. The proposed methodology makes used of Firefly Algorithm and Genetic Algorithm as optimization tools and the Coordinate Modal Assurance Criterion as an objective function. The results show that the proposed combination of Coordinate Modal Assurance Criterion and Firefly Algorithm or Genetic Algorithm can be easily used to identify multiple local structural damages in complex structures. However, the convergence rate becomes slower for the case of multiple damages compared to the case of single damage. The effect of noise on the algorithm is further investigated. It is found that the proposed technique is able to detect the damage location and its severity with high accuracy in the presence of noise, although the convergence rate became slower than in the case when no noise is present. It is also found that the convergence rate of Firefly Algorithm is much faster than that of Genetic Algorithm.

The disc-cutter is a finishing tool for the ultrasonic-cutting of paper honeycomb-core material. The cutting state directly affects the machining accuracy and surface quality of the workpiece. The cutting force is an important physical quantity and the cause of ultrasonic cutting defects of the honeycomb-core material. Due to differences in the mechanical properties and cutting performance of honeycomb-core materials and commonly used metal materials, existing metal-cutting-force models cannot be applied to the calculation of ultrasonic cutting forces in the processing of honeycomb-core materials. In response to this problem&mdash, combined with actual working conditions using the ABAQUS finite element analysis software&mdash, a finite element simulation model of the ultrasonic vibration-assisted cutting force of the disc-cutter on the honeycomb-core material was established, and the cutting curves and values were obtained. The experiment of ultrasonic vibration cutting of the disc-cutter proves that from the surface morphology of the honeycomb core, the milling-width has the greatest influence on the cutting force, and the cutting-depth has the smallest influence on the cutting force. The maximum error between the cutting force experimental results and the finite element simulation results under the same cutting conditions was 13.2%, which means that the established cutting-force finite element model is more accurate and can be used to predict the cutting in honeycomb ultrasonic vibration-assisted cutting-force value. Finally, based on the response surface method, a three-dimensional cutting force prediction model of the ultrasonic cutting honeycomb core of the disc-cutter was established by using the simulation model data. The results of this study can provide a useful basis for the improvement of cutting performance and processing efficiency in the processing of paper honeycomb-core materials.

As a basic mechanical component, the sealing ring is widely used in industrial, aerospatial, and other fields. In this study, an elastic metal C-shaped sealing ring with a wave structure was taken as an example, and its performance was analyzed theoretically and measured experimentally. First, an experimental study was performed on the C-ring seal. The proposed method for experimental measurement of the contact stress of the C-ring seal involved innovative use of a universal electronic testing machine and pressure sensitive paper, in conjunction with the hue&ndash, saturation&ndash, brightness (HSB) method. Based on the discoloration of the pressure sensitive paper after contact stress, computer software was used for analysis, the discoloration was digitized, and the contact stress was established. Second, a theoretical calculation model of the C-ring seal was established using ANSYS software, and a finite element theoretical calculation of the mechanical properties of the sealing ring was established. Finally, the contact stress results were compared with the model calculation results of the C-ring seal. The error between the two was small (4.8%), which proved the validity of the calculation model and the scientificity of the experimental method.

Cockling of paper is a common problem occurring in the production, storage and end-use of paper. It is usually induced by a moisture content change. In many cases, cockling is an irreversible phenomenon; i.e. the initial shape is not obtained although the initial moisture content is restored. This kind of moisture content change occurs in copying machines and in the printing process, for example. In this paper, we present a continuum mechanical model, which is used to study the irreversible cockling of paper. In the model, paper is treated as an orthotropic elasto-plastic material and the model takes into account the small-scale variation of fibre orientation. The model is used to show the importance of the through-thickness moisture gradient on the cockling phenomenon during a cyclic moisture content change. The results suggest that the moisture gradient is a crucial factor for the irreversible cockling.

Corner joints are critical points of wooden structures not only in furniture construction but also in traditional wooden architecture, especially in constructions without nails. This study was performed to determine the effects of particular factors such as the axis of assembly, types of material, and adhesive on the tensile performance of various modern and traditional types of wooden corner joints. For this purpose, various corner joint specimens were prepared with three different wooden materials: Scots pine (Pinus sylvestris Lipsky) wood, Lombardy poplar (Populus nigra Lipsky) wood, and Medium Density Fibreboard (MDF) using two different adhesives: polyvinyl acetate (PVAc) and polyurethane (Desmodur-VTKA) glues; and five different wooden joint types: dowel, tongue-and-groove, half-blind dovetail, screw, and eccentric screw joints. Tensile performance tests, vertical and parallel to the axis of assembly, were carried out according to ASTM D 1037 guidelines. Experiments indicated that, while the tensile performance of MDF specimen connected with a screw and PVAc adhesive was the highest under loading parallel to the axis of assembly (4592 N); it was the lowest under loading parallel to the axis of assembly in MDF specimen connected with tongue-and-groove joint and PVAc adhesive (260 N), respectively. As a result, it may be advantageous to apply screwed joints in corners for high tensile strength in parallel to the axis of the assembly., Kutni su spojevi kritične točke drvnih konstrukcija ne samo u proizvodnji namještaja nego i u tradicionalnoj drvnoj arhitekturi, posebice u konstrukcijama bez čavala. Ovo je istraživanje provedeno kako bi se utvrdili učinci specifičnih čimbenika kao što su os montaže, vrsta materijala i vrsta ljepila na vlačna svojstva različitih modernih i tradicionalnih vrsta drvnih kutnih spojeva. Za tu su svrhu pripremljeni različiti uzorci kutnih spojeva od tri vrste drvnog materijala: od drva bijelog bora (Pinus sylvestris Lipsky), drva lombardijske topole (Populus nigra Lipsky) i od srednje guste ploče vlaknatice (MDF), uz uporabu dvaju različitih ljepila: polivinilacetatnoga (PVAc) i poliuretanskoga (Desmodur-VTKA) te uz pet različitih vrsta drvnih spojeva: moždanika, pera i utora, poluzatvorenog lastina repa, vijka i ekscentra. Ispitivanja vlačnih svojstava okomito i paralelno s osi montaže provedena su u skladu s normom ASTM D 1037. Rezultati su pokazali da su najbolja vlačna svojstva MDF uzorka spojenoga vijkom i PVAc ljepilom pod opterećenjem paralelno s osi montaže (4592 N), a najlošijima su se pokazala vlačna svojstva MDF uzorka spojenoga perom i utorom te PVAc ljepilom pod opterećenjem paralelno s osi montaže (260 N). Prema tome, primjena vijaka u kutnim spojevima može biti dobar izbor za postizanje visoke vlačne čvrstoće paralelno s osi montaže.

The effect of repair techniques on the biomechanics of the aorta is poorly understood, resulting in significant levels of postoperative complications for patients worldwide. This study presents a computational analysis of the influence of Nitinol-based devices on the biomechanical performance of a healthy patient-specific human aorta. Simulations reveal that Nitinol stent-grafts stretch the artery wall so that collagen is stretched to a straightened high-stiffness configuration. The high-compliance regime (HCR) associated with low diastolic lumen pressure is eliminated, and the artery operates in a low-compliance regime (LCR) throughout the entire cardiac cycle. The slope of the lumen pressure–area curve for the LCR post-implantation is almost identical to that of the native vessel during systole. This negligible change from the native LCR slope occurs because the stent-graft increases its diameter from the crimped configuration during deployment so that it reaches a low-stiffness unloading plateau. The effective radial stiffness of the implant along this unloading plateau is negligible compared to the stiffness of the artery wall. Provided the Nitinol device unloads sufficiently during deployment to the unloading plateau, the degree of oversizing has a negligible effect on the pressure–area response of the vessel, as each device exerts approximately the same radial force, the slope of which is negligible compared to the LCR slope of the native artery. We show that 10% oversizing based on the observed diastolic diameter in the mid descending thoracic aorta results in a complete loss of contact between the device and the wall during systole, which could lead to an endoleak and stent migration. 20% oversizing reaches the Dacron enforced area limit (DEAL) during the pulse pressure and results in an effective zero-compliance in the later portion of systole.

This paper reports the performance enhancement benefits in diamond turning of the silicon wafer by incorporation of the surface defect machining (SDM) method. The hybrid micromachining methods usually require additional hardware to leverage the added advantage of hybrid technologies such as laser heating, cryogenic cooling, electric pulse or ultrasonic elliptical vibration. The SDM method tested in this paper does not require any such additional baggage and is easy to implement in a sequential micro-machining mode. This paper made use of Raman spectroscopy data, average surface roughness data and imaging data of the cutting chips of silicon for drawing a comparison between conventional single-point diamond turning (SPDT) and SDM while incorporating surface defects in the (i) circumferential and (ii) radial directions. Complementary 3D finite element analysis (FEA) was performed to analyse the cutting forces and the evolution of residual stress on the machined wafer. It was found that the surface defects generated in the circumferential direction with an interspacing of 1 mm revealed the lowest average surface roughness (Ra) of 3.2 nm as opposed to 8 nm Ra obtained through conventional SPDT using the same cutting parameters. The observation of the Raman spectroscopy performed on the cutting chips showed remnants of phase transformation during the micromachining process in all cases. FEA was used to extract quantifiable information about the residual stress as well as the sub-surface integrity and it was discovered that the grooves made in the circumferential direction gave the best machining performance. The information being reported here is expected to provide an avalanche of opportunities in the SPDT area for low-cost machining solution for a range of other nominal hard, brittle materials such as SiC, ZnSe and GaAs as well as hard steels.

Thoracic endovascular aortic repair (TEVAR) has been accepted as the mainstream treatment for type B aortic dissection, but post-TEVAR biomechanical-related complications are still a major drawback. Unfortunately, the stent-graft (SG) configuration after implantation and biomechanical interactions between the SG and local aorta are usually unknown prior to a TEVAR procedure. The ability to obtain such information via personalised computational simulation would greatly assist clinicians in pre-surgical planning. In this study, a virtual SG deployment simulation framework was developed for the treatment for a complicated aortic dissection case. It incorporates patient-specific anatomical information based on pre-TEVAR CT angiographic images, details of the SG design and the mechanical properties of the stent wire, graft and dissected aorta. Hyperelastic material parameters for the aortic wall were determined based on uniaxial tensile testing performed on aortic tissue samples taken from type B aortic dissection patients. Pre-stress conditions of the aortic wall and the action of blood pressure were also accounted for. The simulated post-TEVAR configuration was compared with follow-up CT scans, demonstrating good agreement with mean deviations of 5.8% in local open area and 4.6 mm in stent strut position. Deployment of the SG increased the maximum principal stress by 24.30 kPa in the narrowed true lumen but reduced the stress by 31.38 kPa in the entry tear region where there was an aneurysmal expansion. Comparisons of simulation results with different levels of model complexity suggested that pre-stress of the aortic wall and blood pressure inside the SG should be included in order to accurately predict the deformation of the deployed SG.

The optic nerve (ON) is a recently recognized tractional load on the eye during larger horizontal eye rotations. In order to understand the mechanical behavior of the eye during adduction, it is necessary to characterize material properties of the sclera, ON, and in particular its sheath. We performed tensile loading of specimens taken from fresh postmortem human eyes to characterize the range of variation in their biomechanical properties and determine the effect of preconditioning. We fitted reduced polynomial hyperelastic models to represent the nonlinear tensile behavior of the anterior, equatorial, posterior, and peripapillary sclera, as well as the ON and its sheath. For comparison, we analyzed tangent moduli in low and high strain regions to represent stiffness. Scleral stiffness generally decreased from anterior to posterior ocular regions. The ON had the lowest tangent modulus, but was surrounded by a much stiffer sheath. The low-strain hyperelastic behaviors of adjacent anatomical regions of the ON, ON sheath, and posterior sclera were similar as appropriate to avoid discontinuities at their boundaries. Regional stiffnesses within individual eyes were moderately correlated, implying that mechanical properties in one region of an eye do not reliably reflect properties of another region of that eye, and that potentially pathological combinations could occur in an eye if regional properties are discrepant. Preconditioning modestly stiffened ocular tissues, except peripapillary sclera that softened. The nonlinear mechanical behavior of posterior ocular tissues permits their stresses to match closely at low strains, although progressively increasing strain causes particularly great stress in the peripapillary region.

Bone tissue exhibits piezoelectric properties and thus is capable of transforming mechanical stress into electrical potential. Piezoelectricity has been shown to play a vital role in bone adaptation and remodelling processes. Therefore, to better understand the interplay between mechanical and electrical stimulation during these processes, strain-adaptive bone remodelling models without and with considering the piezoelectric effect were simulated using the Python-based open-source software framework. To discretise numerical attributes, the finite element method (FEM) was used for the spatial variables and an explicit Euler scheme for the temporal derivatives. The predicted bone apparent density distributions were qualitatively and quantitatively evaluated against the radiographic scan of a human proximal femur and the bone apparent density calculated using a bone mineral density (BMD) calibration phantom, respectively. Additionally, the effect of the initial bone density on the resulting predicted density distribution was investigated globally and locally. The simulation results showed that the electrically stimulated bone surface enhanced bone deposition and these are in good agreement with previous findings from the literature. Moreover, mechanical stimuli due to daily physical activities could be supported by therapeutic electrical stimulation to reduce bone loss in case of physical impairment or osteoporosis. The bone remodelling algorithm implemented using an open-source software framework facilitates easy accessibility and reproducibility of finite element analysis made.

There is an increased interest in studying the biomechanics of the facet joints. For in silico studies, it is therefore important to understand the level of reliability of models for outputs of interest related to the facet joints. In this work, a systematic review of finite element models of multi-level spinal section with facet joints output of interest was performed. The review focused on the methodology used to model the facet joints and its associated validation. From the 110 papers analysed, 18 presented some validation of the facet joints outputs. Validation was done by comparing outputs to literature data, either computational or experimental values; with the major drawback that, when comparing to computational values, the baseline data was rarely validated. Analysis of the modelling methodology showed that there seems to be a compromise made between accuracy of the geometry and nonlinearity of the cartilage behaviour in compression. Most models either used a soft contact representation of the cartilage layer at the joint or included a cartilage layer which was linear elastic. Most concerning, soft contact models usually did not contain much information on the pressure-overclosure law. This review shows that to increase the reliability of in silico model of the spine for facet joints outputs, more needs to be done regarding the description of the methods used to model the facet joints, and the validation for specific outputs of interest needs to be more thorough, with recommendation to systematically share input and output data of validation studies.

The shape optimization of mechanical and automotive component plays a crucial role in the development of automotive technology. Presently, the use of derivative-free metaheuristics in combination with finite element analysis for mechanical component design is one of the most focused on topics due to its simplicity and effectiveness. In this research paper, the mine blast algorithm (MBA) is used to solve the problem of shape optimization for a vehicle door hinge to prove how the MBA can be used for solving shape optimization problems in designing electrical vehicles. The results show the advantage of the MBA for designing optimal components in the automotive industry.

Development and application of advanced mechanical models of soft tissues and their growth represent one of the main directions in modern mechanics of solids. Such models are increasingly used to deal with complex biomedical problems. Prediction of in-stent restenosis for patients treated with coronary stents remains a highly challenging task. Using a finite element method, this paper presents a mechanistic approach to evaluate the development of in-stent restenosis in an artery following stent implantation. Hyperelastic models with damage, verified with experimental results, are used to describe the level of tissue damage in arterial layers and plaque caused by such intervention. A tissue-growth model, associated with vessel damage, is adopted to describe the growth behaviour of a media layer after stent implantation. Narrowing of lumen diameter with time is used to quantify the development of in-stent restenosis in the vessel after stenting. It is demonstrated that stent designs and materials strongly affect the stenting-induced damage in the media layer and the subsequent development of in-stent restenosis. The larger the artery expansion achieved during balloon inflation, the higher the damage introduced to the media layer, leading to an increased level of in-stent restenosis. In addition, the development of in-stent restenosis is directly correlated with the artery expansion during the stent deployment. The correlation is further used to predict the effect of a complex clinical procedure, such as stent overlapping, on the level of in-stent restenosis developed after percutaneous coronary intervention.

Lumbar ligaments play a key role in stabilizing the spine, particularly assisting muscles at wide-range movements. Hence, valid ligament force–strain data are required to generate physiological model predictions. These data have been obtained by experiments on single ligaments or functional units throughout the literature. However, contrary to detailed spine geometries, gained, for instance, from CT data, ligament characteristics are often inattentively transferred to multi-body system (MBS) or finite element models. In this paper, we use an elaborated MBS model of the lumbar spine to demonstrate how individualized ligament characteristics can be obtained by reversely reenacting stepwise reduction experiments, where the range of motion (ROM) was measured. We additionally validated the extracted characteristics with physiological experiments on intradiscal pressure (IDP). Our results on a total of in each case 160 ROM and 49 IDP simulations indicated superiority of our procedure (seven and eight outliers) toward the incorporation of classical literature data (on average 71 and 31 outliers).

Objective This brief review essay was triggered by the discovery of two errors that have been perpetuated in the dental literature for the last quarter century and is intended to alert the research community. Methods An extensive search of the published literature, using PubMed and Web of Science search engines, electronic journal resources, and several trips to the library for manual retrievals of articles were used to retrieve hundreds of articles reporting on finite element modeling – finite element analysis (FEM/FEA) involving periodontal ligament (PDL) and gutta percha (GP). Results The literature search revealed that erroneous values for the modulus of elasticity of PDL and GP were introduced in 1980 and in 1983, respectively. The identified errors range between two to three orders of magnitude and have been used in hundreds of FEM/FEA papers. Significance The finding casts serious doubts regarding the validity of the results published in hundreds of papers and highlights the importance of checking the references cited and citing, or at least confirming, primary sources rather than citing citations.

Probing mechanical properties of cells has been identified as a means to infer information on their current state, e.g. with respect to diseases or differentiation. Oocytes have gained particular interest, since mechanical parameters are considered potential indicators of the success of in vitro fertilisation procedures. Established tests provide the structural response of the oocyte resulting from the material properties of the cell’s components and their disposition. Based on dedicated experiments and numerical simulations, we here provide novel insights on the origin of this response. In particular, polarised light microscopy is used to characterise the anisotropy of the zona pellucida, the outermost layer of the oocyte composed of glycoproteins. This information is combined with data on volumetric changes and the force measured in relaxation/cyclic, compression/indentation experiments to calibrate a multi-phasic hyper-viscoelastic model through inverse finite element analysis. These simulations capture the oocyte’s overall force response, the distinct volume changes observed in the zona pellucida, and the structural alterations interpreted as a realignment of the glycoproteins with applied load. The analysis reveals the presence of two distinct timescales, roughly separated by three orders of magnitude, and associated with a rapid outflow of fluid across the external boundaries and a long-term, progressive relaxation of the glycoproteins, respectively. The new results allow breaking the overall response down into the contributions from fluid transport and the mechanical properties of the zona pellucida and ooplasm. In addition to the gain in fundamental knowledge, the outcome of this study may therefore serve an improved interpretation of the data obtained with current methods for mechanical oocyte characterisation.

New treatments for bone diseases require testing in animal models before clinical translation, and the mouse tibia is among the most common models. In vivo micro-Computed Tomography (microCT)-based micro-Finite Element (microFE) models can be used for predicting the bone strength non-invasively, after proper validation against experimental data. Different modelling techniques can be used to estimate the bone properties, and the accuracy associated with each is unclear. The aim of this study was to evaluate the ability of different microCT-based microFE models to predict the mechanical properties of the mouse tibia under compressive load. Twenty tibiae were microCT scanned at 10.4 µm voxel size and subsequently compressed at 0.03 mm/s until failure. Stiffness and failure load were measured from the load–displacement curves. Different microFE models were generated from each microCT image, with hexahedral or tetrahedral mesh, and homogeneous or heterogeneous material properties. Prediction accuracy was comparable among models. The best correlations between experimental and predicted mechanical properties, as well as lower errors, were obtained for hexahedral models with homogeneous material properties. Experimental stiffness and predicted stiffness were reasonably well correlated (R2 = 0.53–0.65, average error of 13–17%). A lower correlation was found for failure load (R2 = 0.21–0.48, average error of 9–15%). Experimental and predicted mechanical properties normalized by the total bone mass were strongly correlated (R2 = 0.75–0.80 for stiffness, R2 = 0.55–0.81 for failure load). In conclusion, hexahedral models with homogeneous material properties based on in vivo microCT images were shown to best predict the mechanical properties of the mouse tibia.

Cardiac growth is an important mechanism for the human body to respond to changes in blood flow demand. Being able to predict the development of chronic growth is clinically relevant, but so far models to predict growth have not reached consensus on the stimulus–effect relation. In a previously published study, we modeled cardiac and hemodynamic function through a lumped parameter approach. We evaluated cardiac growth in response to valve disease using various stimulus–effect relations and observed an unphysiological decline pump function. Here we extend that model with a model of hemodynamic feedback that maintains mean arterial pressure and cardiac output through adaptation of peripheral resistance and circulatory unstressed volume. With the combined model, we obtain stable growth and restoration of pump function for most growth laws. We conclude that a mixed combination of stress and strain stimuli to drive cardiac growth is most promising since it (1) reproduces clinical observations on cardiac growth well, (2) requires only a small, clinically realistic adaptation of the properties of the circulatory system and (3) is robust in the sense that results were fairly insensitive to the exact choice of the chosen mechanics loading measure. This finding may be used to guide the choice of growth laws in more complex finite element models of cardiac growth, suitable for predicting the response to spatially varying changes in tissue load. Eventually, the current model may form a basis for a tool to predict patient-specific growth in response to spatially homogeneous changes in tissue load, since it is computationally inexpensive.

The frictional response of porous and permeable hydrated biological tissues such as articular cartilage is significantly dependent on interstitial fluid pressurization. To model this response, it is common to represent such tissues as biphasic materials, consisting of a binary mixture of a porous solid matrix and an interstitial fluid. However, no computational algorithms currently exist in either commercial or open-source software that can model frictional contact between such materials. Therefore, this study formulates and implements a finite element algorithm for large deformation biphasic frictional contact in the open-source finite element software FEBio. This algorithm relies on a local form of a biphasic friction model that has been previously validated against experiments, and implements the model into our recently-developed surface-to-surface (STS) contact algorithm. Contact constraints, including those specific to pressurized porous media, are enforced with the penalty method regularized with an active–passive augmented Lagrangian scheme. Numerical difficulties specific to challenging finite deformation biphasic contact problems are overcome with novel smoothing schemes for fluid pressures and Lagrange multipliers. Implementation accuracy is verified against semi-analytical solutions for biphasic frictional contact, with extensive validation performed using canonical cartilage friction experiments from prior literature. Essential details of the formulation are provided in this paper, and the source code of this biphasic frictional contact algorithm is made available to the general public.

Finite element head (FE) models are important numerical tools to study head injuries and develop protection systems. The generation of anatomically accurate and subject-specific head models with conforming hexahedral meshes remains a significant challenge. The focus of this study is to present two developmental works: first, an anatomically detailed FE head model with conforming hexahedral meshes that has smooth interfaces between the brain and the cerebrospinal fluid, embedded with white matter (WM) fiber tracts; second, a morphing approach for subject-specific head model generation via a new hierarchical image registration pipeline integrating Demons and Dramms deformable registration algorithms. The performance of the head model is evaluated by comparing model predictions with experimental data of brain–skull relative motion, brain strain, and intracranial pressure. To demonstrate the applicability of the head model and the pipeline, six subject-specific head models of largely varying intracranial volume and shape are generated, incorporated with subject-specific WM fiber tracts. DICE similarity coefficients for cranial, brain mask, local brain regions, and lateral ventricles are calculated to evaluate personalization accuracy, demonstrating the efficiency of the pipeline in generating detailed subject-specific head models achieving satisfactory element quality without further mesh repairing. The six head models are then subjected to the same concussive loading to study the sensitivity of brain strain to inter-subject variability of the brain and WM fiber morphology. The simulation results show significant differences in maximum principal strain and axonal strain in local brain regions (one-way ANOVA test, p

A computational strategy based on the finite element method for simulating the mechanical response of arterial tissues is herein proposed. The adopted constitutive formulation accounts for rotations of the adventitial collagen fibers and introduces parameters which are directly measurable or well established. Moreover, the refined constitutive model is readily utilized in finite element analyses, enabling the simulation of mechanical tests to reveal the influence of microstructural and histological features on macroscopic material behavior. Employing constitutive parameters supported by histological examinations, the results herein validate the model’s ability to predict the micro- and macroscopic mechanical behavior, closely matching previously observed experimental findings. Finally, the capabilities of the adopted constitutive description are shown investigating the influence of some collagen disorders on the macroscopic mechanical response of the arterial tissues.

Head rotational kinematics and tissue deformation metrics obtained from finite element models (FEM) have the potential to be used as traumatic axonal injury (TAI) assessment criteria and headgear evaluation standards. These metrics have been used to predict the likelihood of TAI occurrence; however, their ability in the assessment of the extent of TAI has not been explored. In this study, a pig model of TAI was used to examine a wide range of head loading conditions in two directions. The extent of TAI was quantified through histopathology and correlated to the FEM-derived tissue deformations and the head rotational kinematics. Peak angular acceleration and maximum strain rate of axonal fiber and brain tissue showed relatively good correlation to the volume of axonal injury, with similar correlation trends for both directions separately or combined. These rotational kinematics and tissue deformations can estimate the extent of acute TAI. The relationships between the head kinematics and the tissue strain, strain rate, and strain times strain rate were determined over the experimental range examined herein, and beyond that through parametric simulations. These relationships demonstrate that peak angular velocity and acceleration affect the underlying tissue deformations and the knowledge of both help to predict TAI risk. These relationships were combined with the injury thresholds, extracted from the TAI risk curves, and the kinematic-based risk curves representing overall axonal and brain tissue strain and strain rate were determined for predicting TAI. After scaling to humans, these curves can be used for real-time TAI assessment.

Delayed long bone fracture healing and nonunion continue to be a significant socioeconomic burden. While mechanical stimulation is known to be an important determinant of the bone repair process, understanding how the magnitude, mode, and commencement of interfragmentary strain (IFS) affect fracture healing can guide new therapeutic strategies to prevent delayed healing or nonunion. Mouse models provide a means to investigate the molecular and cellular aspects of fracture repair, yet there is only one commercially available, clinically-relevant, locking intramedullary nail (IMN) currently available for studying long bone fractures in rodents. Having access to alternative IMNs would allow a variety of mechanical environments at the fracture site to be evaluated, and the purpose of this proof-of-concept finite element analysis study is to identify which IMN design parameters have the largest impact on IFS in a murine transverse femoral osteotomy model. Using the dimensions of the clinically relevant IMN as a guide, the nail material, distance between interlocking screws, and clearance between the nail and endosteal surface were varied between simulations. Of these parameters, changing the nail material from stainless steel (SS) to polyetheretherketone (PEEK) had the largest impact on IFS. Reducing the distance between the proximal and distal interlocking screws substantially affected IFS only when nail modulus was low. Therefore, IMNs with low modulus (e.g., PEEK) can be used alongside commercially available SS nails to investigate the effect of initial IFS or stability on fracture healing with respect to different biological conditions of repair in rodents.

Sandwich structures with Miura-ori cores have been studied especially in aerospace industry. However, by removing the face sheets one can obtain esthetical, multifunctional, self-supporting structures for various applications, such as packaging. This study focuses on the mechanical performance of planar, self-supporting Miura-ori structures under compressive loads. Through systematic variations of both origami geometry and base material orientation, this study performs linear stress and stability analyses by utilizing the finite element method. The results reveal the effects of the geometric parameters and the material orthotropy on the structural performance, finally resulting in parameter ranges forming a basis for structural design.

The press-section of a paper machine holds several different types of press rolls. One of the many press roll variants is the Valmet produced press roll, ViscoNip. This press roll utilizes an extended nip in order to increase the amount of water removed. The extended press nip in ViscoNip is special since it is controllable by a pressurized polyurethane press shoe. The press shoe runs through the body of the press roll. Due to limits of the current production process, new manufacturing methods and construction solutions are needed. In cooperation with another thesis, the current design and manufacturing process was reviewed and a plan intended to improve the current solution was formulated. The plan was to, by working together in a project, perform a product development process intended to create concepts able to utilize new methods of manufacturing. By using established methods of concept generation, such as Brainwriting 6-3-5, 11 concepts were created. Some of these concepts involved a redesign of the press shoe, leading to a need for construction and performance analysis. With the other thesis focusing on researching new possible and available manufacturing solutions. The work of this thesis fully committed to the structural and mechanical performance evaluation of the new concepts. This was performed by creating a model of the technical application using Finite Element Modelling in ABAQUS. The model included a hyperelastic material model for the polyurethane material as well as cohesive zone modelling to account for partitioning of the part. The model was then used to simulate the different concepts as they were subjected to a challenging load case. The results of which were used as the basis for structural and performance analysis. The analysis showed proof of sufficient structural stability and mechanical performance for all evaluated concepts. Then, in cooperation with the other thesis, a final concept choice was made. All in all, three different redesigned concepts were deemed as having potential for further development. The current solution was also deemed as having potential for future development but only when new manufacturing methods or techniques were considered.

Mixture theory is a general framework that has been used to model mixtures of solid, fluid, and solute constituents, leading to significant advances in modeling the mechanics of biological tissues and cells. Though versatile and applicable to a wide range of problems in biomechanics and biophysics, standard multiphasic mixture frameworks incorporate neither dynamics of viscous fluids nor fluid compressibility, both of which facilitate the finite element implementation of computational fluid dynamics solvers. This study formulates governing equations for reactive multiphasic mixtures where the interstitial fluid has a solvent which is viscous and compressible. This hybrid reactive multiphasic framework uses state variables that include the deformation gradient of the porous solid matrix, the volumetric strain and rate of deformation of the solvent, the solute concentrations, and the relative velocities between the various constituents. Unlike standard formulations which employ a Lagrange multiplier to model fluid pressure, this framework requires the formulation of a function of state for the pressure, which depends on solvent volumetric strain and solute concentrations. Under isothermal conditions the formulation shows that the solvent volumetric strain remains continuous across interfaces between hybrid multiphasic domains. Apart from the Lagrange multiplier-state function distinction for the fluid pressure, and the ability to accommodate viscous fluid dynamics, this hybrid multiphasic framework remains fully consistent with standard multiphasic formulations previously employed in biomechanics. With these additional features, the hybrid multiphasic mixture theory makes it possible to address a wider range of problems that are important in biomechanics and mechanobiology.

Living soft tissues appear to promote the development and maintenance of a preferred mechanical state within a defined tolerance around a so-called set point. This phenomenon is often referred to as mechanical homeostasis. In contradiction to the prominent role of mechanical homeostasis in various (patho)physiological processes, its underlying micromechanical mechanisms acting on the level of individual cells and fibers remain poorly understood, especially how these mechanisms on the microscale lead to what we macroscopically call mechanical homeostasis. Here, we present a novel computational framework based on the finite element method that is constructed bottom up, that is, it models key mechanobiological mechanisms such as actin cytoskeleton contraction and molecular clutch behavior of individual cells interacting with a reconstructed three-dimensional extracellular fiber matrix. The framework reproduces many experimental observations regarding mechanical homeostasis on short time scales (hours), in which the deposition and degradation of extracellular matrix can largely be neglected. This model can serve as a systematic tool for future in silico studies of the origin of the numerous still unexplained experimental observations about mechanical homeostasis.

The phenomenological model for cell shape deformation and cell migration Chen (BMM 17:1429–1450, 2018), Vermolen and Gefen (BMM 12:301–323, 2012), is extended with the incorporation of cell traction forces and the evolution of cell equilibrium shapes as a result of cell differentiation. Plastic deformations of the extracellular matrix are modelled using morphoelasticity theory. The resulting partial differential differential equations are solved by the use of the finite element method. The paper treats various biological scenarios that entail cell migration and cell shape evolution. The experimental observations in Mak et al. (LC 13:340–348, 2013), where transmigration of cancer cells through narrow apertures is studied, are reproduced using a Monte Carlo framework.

An efficient solver for large-scale linear \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\mu \hbox {FE}$$\end{document}μFE simulations was extended for nonlinear material behavior. The material model included damage-based tissue degradation and fracture. The new framework was applied to 20 trabecular biopsies with a mesh resolution of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${36}\,{{\upmu }\hbox {m}}$$\end{document}36μm. Suitable material parameters were identified based on two biopsies by comparison with axial tension and compression experiments. The good parallel performance and low memory footprint of the solver were preserved. Excellent correlation of the maximum apparent stress was found between simulations and experiments (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$R^2 > 0.97$$\end{document}R2>0.97). The development of local damage regions was observable due to the nonlinear nature of the simulations. A novel elasticity limit was proposed based on the local damage information. The elasticity limit was found to be lower than the 0.2% yield point. Systematic differences in the yield behavior of biopsies under apparent compression and tension loading were observed. This indicates that damage distributions could lead to more insight into the failure mechanisms of trabecular bone.

In many fiber-reinforced tissues, collagen fibers are embedded within a glycosaminoglycan-rich extrafibrillar matrix. Knowledge of the structure–function relationship between the sub-tissue properties and bulk tissue mechanics is important for understanding tissue failure mechanics and developing biological repair strategies. Difficulties in directly measuring sub-tissue properties led to a growing interest in employing finite element modeling approaches. However, most models are homogeneous and are therefore not sufficient for investigating multiscale tissue mechanics, such as stress distributions between sub-tissue structures. To address this limitation, we developed a structure-based model informed by the native annulus fibrosus structure, where fibers and the matrix were described as distinct materials occupying separate volumes. A multiscale framework was applied such that the model was calibrated at the sub-tissue scale using single-lamellar uniaxial mechanical test data, while validated at the bulk scale by predicting tissue multiaxial mechanics for uniaxial tension, biaxial tension, and simple shear (13 cases). Structure-based model validation results were compared to experimental observations and homogeneous models. While homogeneous models only accurately predicted bulk tissue mechanics for one case, structure-based models accurately predicted bulk tissue mechanics for 12 of 13 cases, demonstrating accuracy and robustness. Additionally, six of eight structure-based model parameters were directly linked to tissue physical properties, further broadening its future applicability. In conclusion, the structure-based model provides a powerful multiscale modeling approach for simultaneously investigating the structure–function relationship at the sub-tissue and bulk tissue scale, which is important for studying multiscale tissue mechanics with degeneration, disease, or injury. Electronic supplementary material The online version of this article (10.1007/s10237-019-01246-x) contains supplementary material, which is available to authorized users.

Sagittal craniosynostosis consists of premature fusion (ossification) of the sagittal suture during infancy, resulting in head deformity and brain growth restriction. Spring-assisted cranioplasty (SAC) entails skull incisions to free the fused suture and insertion of two springs (metallic distractors) to promote cranial reshaping. Although safe and effective, SAC outcomes remain uncertain. We aimed hereby to obtain and validate a skull material model for SAC outcome prediction. Computed tomography data relative to 18 patients were processed to simulate surgical cuts and spring location. A rescaling model for age matching was created using retrospective data and validated. Design of experiments was used to assess the effect of different material property parameters on the model output. Subsequent material optimization—using retrospective clinical spring measurements—was performed for nine patients. A population-derived material model was obtained and applied to the whole population. Results showed that bone Young’s modulus and relaxation modulus had the largest effect on the model predictions: the use of the population-derived material model had a negligible effect on improving the prediction of on-table opening while significantly improved the prediction of spring kinematics at follow-up. The model was validated using on-table 3D scans for nine patients: the predicted head shape approximated within 2 mm the 3D scan model in 80% of the surface points, in 8 out of 9 patients. The accuracy and reliability of the developed computational model of SAC were increased using population data: this tool is now ready for prospective clinical application.

It has been proposed that finite element analysis can complement clinical decision making for the appropriate design and manufacture of prosthetic sockets for amputees. However, clinical translation has not been achieved, in part due to lengthy solver times and the complexity involved in model development. In this study, a parametric model was created, informed by variation in (i) population-driven residuum shape morphology, (ii) soft tissue compliance and (iii) prosthetic socket design. A Kriging surrogate model was fitted to the response of the analyses across the design space enabling prediction for new residual limb morphologies and socket designs. It was predicted that morphological variability and prosthetic socket design had a substantial effect on socket-limb interfacial pressure and shear conditions as well as sub-dermal soft tissue strains. These relationships were investigated with a higher resolution of anatomical, surgical and design variability than previously reported, with a reduction in computational expense of six orders of magnitude. This enabled real-time predictions (1.6 ms) with error vs the analytical solutions of

This study analyzes the lethal clinical condition of aortic dissections from a numerical point of view. On the basis of previous contributions by Gültekin et al. (Comput Methods Appl Mech Eng 312:542-566, 2016 and 331:23-52, 2018), we apply a holistic geometrical approach to fracture, namely the crack phase-field, which inherits the intrinsic features of gradient damage and variational fracture mechanics. The continuum framework captures anisotropy, is thermodynamically consistent and is based on finite strains. The balance of linear momentum and the crack evolution equation govern the coupled mechanical and phase-field problem. The solution scheme features the robust one-pass operator-splitting algorithm upon temporal and spatial discretizations. Based on experimental data of diseased human thoracic aortic samples, the elastic material parameters are identified followed by a sensitivity analysis of the anisotropic phase-field model. Finally, we simulate an incipient propagation of an aortic dissection within a multi-layered segment of a thoracic aorta that involves a prescribed initial tear. The finite element results demonstrate a severe damage zone around the initial tear and exhibit a rather helical crack pattern, which aligns with the fiber orientation. It is hoped that the current contribution can provide some directions for further investigations of this disease.

Bulk properties of cortical bone have been well characterized experimentally, and potent toughening mechanisms, e.g., crack deflections, have been identified at the microscale. However, it is currently difficult to experimentally measure local damage properties and isolate their effect on the tissue fracture resistance. Instead, computer models can be used to analyze the impact of local characteristics and structures, but material parameters required in computer models are not well established. The aim of this study was therefore to identify the material parameters that are important for crack propagation in cortical bone and to elucidate what parameters need to be better defined experimentally. A comprehensive material parameter study was performed using an XFEM interface damage model in 2D to simulate crack propagation around an osteon at the microscale. The importance of 14 factors (material parameters) on four different outcome criteria (maximum force, fracture energy, crack length and crack trajectory) was evaluated using ANOVA for three different osteon orientations. The results identified factors related to the cement line to influence the crack propagation, where the interface strength was important for the ability to deflect cracks. Crack deflection was also favored by low interface stiffness. However, the cement line properties are not well determined experimentally and need to be better characterized. The matrix and osteon stiffness had no or low impact on the crack pattern. Furthermore, the results illustrated how reduced matrix toughness promoted crack penetration of the cement line. This effect is highly relevant for the understanding of the influence of aging on crack propagation and fracture resistance in cortical bone. Electronic supplementary material The online version of this article (10.1007/s10237-019-01142-4) contains supplementary material, which is available to authorized users.

Made available in DSpace on 2022-04-29T08:41:17Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-10-01 Dental interfaces are subject to mixed-mode loading. This study provides practical guidance for determining interfacial fracture toughness of dental ceramic systems. We address interfacial fracture of a composite resin cement sandwiched between two dental ceramic materials. Emphasis is placed on sandwich disc specimens with cracks originating from elliptical-shaped flaws near the center, for which analytical fracture mechanics methods fail to predict. The interaction integral method is used to provide accurate finite element solutions for cracks with elliptical-shaped flaws in a Brazil-nut-sandwich specimen. The developed model was first validated with existing experimental data and then used to evaluate the three most widely used dental ceramic systems: polycrystalline ceramics (zirconia), glass-ceramics (lithium disilicate), and feldspathic ceramics (porcelain). Contrary to disc specimens with ideal cracks, those with cracks emanating from elliptical-shaped flaws do not exhibit a monotonic increase in interfacial toughness. Also, interfacial fracture toughness is seen to have a direct relationship with the aspect ratio of elliptical-shaped flaws and an inverse relationship with the modulus ratio of the constituents. The presence of an elliptical-shaped flaw significantly changes the interfacial fracture behavior of sandwich structures. Semi-empirical design equations are provided for fracture toughness and stress intensity factors for interfacial cracks. The developed design equations provide practical guidance for determining interfacial fracture toughness of selected dental ceramic material systems. Those equations take into account four critical factors: size of the elliptical flaw, modulus ratio of constituent materials, loading angle, and applied load. Department of Civil and Environmental Engineering University of Connecticut, 261 Glenbrook Road, U-3037 Department of Dental Materials and Prosthodontics Institute of Science and Technology of Sao Jose dos Campos Sao Paulo State University (UNESP), SP Department of Preventive and Restorative Sciences School of Dental Medicine University of Pennsylvania Department of Dental Materials and Prosthodontics Institute of Science and Technology of Sao Jose dos Campos Sao Paulo State University (UNESP), SP

The sensory hairs of the Venus flytrap (Dionaea muscipula Ellis) detect mechanical stimuli imparted by their prey and fire bursts of electrical signals called action potentials (APs). APs are elicited when the hairs are sufficiently stimulated and two consecutive APs can trigger closure of the trap. Earlier experiments have identified thresholds for the relevant stimulus parameters, namely the angular displacement $$\theta $$ θ and angular velocity $$\omega $$ ω . However, these experiments could not trace the deformation of the trigger hair’s sensory cells, which are known to transduce the mechanical stimulus. To understand the kinematics at the cellular level, we investigate the role of two relevant mechanical phenomena: viscoelasticity and intercellular fluid transport using a multi-scale numerical model of the sensory hair. We hypothesize that the combined influence of these two phenomena and $$\omega $$ ω contribute to the flytrap’s rate-dependent response to stimuli. In this study, we firstly perform sustained deflection tests on the hair to estimate the viscoelastic material properties of the tissue. Thereafter, through simulations of hair deflection tests at different loading rates, we were able to establish a multi-scale kinematic link between $$\omega $$ ω and the cell wall stretch $$\delta $$ δ . Furthermore, we find that the rate at which $$\delta $$ δ evolves during a stimulus is also proportional to $$\omega $$ ω . This suggests that mechanosensitive ion channels, expected to be stretch-activated and localized in the plasma membrane of the sensory cells, could be additionally sensitive to the rate at which stretch is applied.

Healing in soft biological tissues is a chain of events on different time and length scales. This work presents a computational framework to capture and couple important mechanical, chemical and biological aspects of healing. A molecular-level damage in collagen, i.e., the interstrand delamination, is addressed as source of plastic deformation in tissues. This mechanism initiates a biochemical response and starts the chain of healing. In particular, damage is considered to be the stimulus for the production of matrix metalloproteinases and growth factors which in turn, respectively, degrade and produce collagen. Due to collagen turnover, the volume of the tissue changes, which can result either in normal or pathological healing. To capture the mechanisms on continuum scale, the deformation gradient is multiplicatively decomposed in inelastic and elastic deformation gradients. A recently proposed elasto-plastic formulation is, through a biochemical model, coupled with a growth and remodeling description based on homogenized constrained mixtures. After the discussion of the biological species response to the damage stimulus, the framework is implemented in a mixed nonlinear finite element formulation and a biaxial tension and an indentation tests are conducted on a prestretched flat tissue sample. The results illustrate that the model is able to describe the evolutions of growth factors and matrix metalloproteinases following damage and the subsequent growth and remodeling in the respect of equilibrium. The interplay between mechanical and chemo-biological events occurring during healing is captured, proving that the framework is a suitable basis for more detailed simulations of damage-induced tissue response.

Rupture risk assessment of abdominal aortic aneurysms (AAAs) by means of quantifying wall stress is a common biomechanical strategy. However, the clinical translation of this approach has been greatly limited due to the complexity associated with the computational tools required for its implementation. Thus, being able to estimate wall stress using nonbiomechanical markers that can be quantified as a direct outcome of clinical image segmentation would be advantageous in improving the potential implementation of said strategy. In the present work, we investigated the use of geometric indices to predict patient-specific AAA wall stress by means of a novel neural network (NN) modeling approach. We conducted a retrospective review of existing clinical images of two patient groups: 98 asymptomatic and 50 symptomatic AAAs. The images were subject to a protocol consisting of image segmentation, processing, volume meshing, finite element modeling, and geometry quantification, from which 53 geometric indices and the spatially averaged wall stress (SAWS) were calculated. SAWS estimated from finite element analysis was considered the gold standard for the predictions. We developed feed-forward NN models composed of an input layer, two dense layers, and an output layer using Keras, a deep learning library in python. The NN models were trained, tested, and validated independently for both AAA groups using all geometric indices, as well as a reduced set of indices resulting from a variable reduction procedure. We compared the performance of the NN models with two standard machine learning algorithms (MARS: multivariate adaptive regression splines and GAM: generalized additive model) and a linear regression model (GLM: generalized linear model). With the reduced sets of indices, the NN-based approach exhibited the highest mean goodness-of-fit (for the symptomatic group 0.71 and for the asymptomatic group 0.79) and lowest mean relative error (17% for both groups). In contrast, MARS yielded a mean goodness-of-fit of 0.59 for the symptomatic group and 0.77 for the asymptomatic group, with relative errors of 17% for the symptomatic group and 22% for the asymptomatic group. GAM had a mean goodness-of-fit of 0.70 for the symptomatic group and 0.80 for the asymptomatic group, with relative errors of 16% for the symptomatic group and 20% for the asymptomatic group. GLM did not perform as well as the other algorithms, with a mean goodness-of-fit of 0.53 for the symptomatic group and 0.70 for the asymptomatic group, with relative errors of 19% for the symptomatic group and 23% for the asymptomatic group. Nevertheless, the NN models required a reduced set of 15 and 13 geometric indices to predict SAWS for the symptomatic and asymptomatic AAA groups, respectively. This was in contrast to the reduced set of nine and eight geometric indices required to predict SAWS with the MARS and GAM algorithms for each AAA group, respectively. The use of NN modeling represents a promising alternative methodology for the estimation of AAA wall stress using geometric indices as surrogates, in lieu of finite element modeling. The performance metrics of NN models are expected to improve with significantly larger group sizes, given the suitability of NN modeling for “big data” applications.

This paper describes a new method for estimating anisotropic mechanical properties of fibrous soft tissue by imaging shear waves induced by focused ultrasound (FUS) and analyzing their direction-dependent speeds. Fibrous materials with a single, dominant fiber direction may exhibit anisotropy in both shear and tensile moduli, reflecting differences in the response of the material when loads are applied in different directions. The speeds of shear waves in such materials depend on the propagation and polarization directions of the waves relative to the dominant fiber direction. In this study, shear waves were induced in muscle tissue (chicken breast) ex vivo by harmonically oscillating the amplitude of an ultrasound beam focused in a cylindrical tissue sample. The orientation of the fiber direction relative to the excitation direction was varied by rotating the sample. Magnetic resonance elastography (MRE) was used to visualize and measure the full 3D displacement field due to the ultrasound-induced shear waves. The phase gradient (PG) of radially propagating “slow” and “fast” shear waves provided local estimates of their respective wave speeds and directions. The equations for the speeds of these waves in an incompressible, transversely isotropic (TI), linear elastic material were fitted to measurements to estimate the shear and tensile moduli of the material. The combination of focused ultrasound and MR imaging allows noninvasive, but comprehensive, characterization of anisotropic soft tissue.

In this paper, we extend the model of wound healing by Boon et al. (J Biomech 49(8):1388–1401, 2016). In addition to explaining the model explicitly regarding every component, namely cells, signalling molecules and tissue bundles, we categorized fibroblasts as regular fibroblasts and myofibroblasts. We do so since it is widely documented that myofibroblasts play a significant role during wound healing and skin contraction and that they are the main phenotype of cells that is responsible for the permanent deformations. Furthermore, we carried out some sensitivity tests of the model by modifying certain parameter values, and we observe that the model shows some consistency with several biological phenomena. Using Monte Carlo simulations, we found that there is a significant strong positive correlation between the final wound area and the minimal wound area. The high correlation between the wound area after 4 days and the final/minimal wound area makes it possible for physicians to predict the most probable time evolution of the wound of the patient. However, the collagen density ratio at the time when the wound area reaches its equilibrium and minimum, cannot indicate the degree of wound contractions, whereas at the 4th day post-wounding, when the collagen is accumulating from null, there is a strong negative correlation between the area and the collagen density ratio. Further, under the circumstances that we modelled, the probability that patients will end up with 5% contraction is about 0.627.

In this paper, we perform flexible and reliable dynamics simulations on different sizes of two or more particles’ interactive motions, where they encounter positive or negative dielectrophoresis (DEP) forces. The particles with identical or non-identical size are in close proximity suspended freely in a solution under a homogeneous electric field. According to the description of classic dipole moment, DEP forces make the particles form a straight chain. Therefore, dynamics simulation based on Newton’s laws is utilized to understand AC DEP phenomena among multiple particles. To solve the relevant governing equations, Stokes drag and repulsive forces (including wall and particles) are combined with DEP forces to obtain the trajectories of particles. Results show that particles with the same sign of the Clausius–Mossotti (CM) factor revolve clockwise or counterclockwise to attract each other parallel to the electric field direction. Conversely, the particle chain is perpendicular to the field. This programmable advantage is of great benefit to the study of three or four particle motions. Meanwhile, the pearl chain consisting of three or four particles is related not only to an individual CM factor but also to initial spatial configuration. Both the cluster and short chain are dependent on symmetry between the geometric distribution and electric field, while it implies different size particles easily cause the chain structure with less time. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10867-018-9514-7) contains supplementary material, which is available to authorized users.

Background and Purpose To date, proposed in silico models for preclinical cardiac safety testing are limited in their predictability and usability. We previously reported a multi‐scale heart simulation that accurately predicts arrhythmogenic risk for benchmark drugs. Experimental Approach We created a comprehensive hazard map of drug‐induced arrhythmia based on the electrocardiogram (ECG) waveforms simulated under wide range of drug effects using the multi‐scale heart simulator described here, implemented with cell models of human cardiac electrophysiology. Key Results A total of 9075 electrocardiograms constitute the five‐dimensional hazard map, with coordinates representing the extent of the block of each of the five ionic currents (rapid delayed rectifier potassium current (I Kr), fast (I Na) and late (I Na,L) components of the sodium current, L‐type calcium current (I Ca,L) and slow delayed rectifier current (I Ks)), involved in arrhythmogenesis. Results of the evaluation of arrhythmogenic risk based on this hazard map agreed well with the risk assessments reported in the literature. ECG databases also suggested that the interval between the J‐point and the T‐wave peak is a superior index of arrhythmogenicity when compared to the QT interval due to its ability to characterize the multi‐channel effects compared with QT interval. Conclusion and Implications Because concentration‐dependent effects on electrocardiograms of any drug can be traced on this map based on in vitro current assay data, its arrhythmogenic risk can be evaluated without performing costly and potentially risky human electrophysiological assays. Hence, the map serves as a novel tool for use in pharmaceutical research and development.

Critical-sized bone defects are critical healing conditions that, if left untreated, often lead to non-unions. To reduce the risk, critical-sized bone defects are often treated with recombinant human BMP-2. Although enhanced bone tissue formation is observed when BMP-2 is administered locally to the defect, spatial and temporal distribution of callus tissue often differs from that found during regular bone healing or in defects treated differently. How this altered tissue patterning due to BMP-2 treatment is linked to mechano-biological principles at the cellular scale remains largely unknown. In this study, the mechano-biological regulation of BMP-2-treated critical-sized bone defect healing was investigated using a multiphysics multiscale in silico approach. Finite element and agent-based modeling techniques were combined to simulate healing within a critical-sized bone defect (5 mm) in a rat femur. Computer model predictions were compared to in vivo microCT data outcome of bone tissue patterning at 2, 4, and 6 weeks postoperation. In vivo, BMP-2 treatment led to complete healing through periosteal bone bridging already after 2 weeks postoperation. Computer model simulations showed that the BMP-2 specific tissue patterning can be explained by the migration of mesenchymal stromal cells to regions with a specific concentration of BMP-2 (chemotaxis). This study shows how computational modeling can help us to further understand the mechanisms behind treatment effects on compromised healing conditions as well as to optimize future treatment strategies. ispartof: BIOMECHANICS AND MODELING IN MECHANOBIOLOGY vol:20 issue:4 pages:1627-1644 ispartof: location:Germany status: published

Large bone defects remain a clinical challenge because they do not heal spontaneously. 3-D printed scaffolds are a promising treatment option for such critical defects. Recent scaffold design strategies have made use of computer modelling techniques to optimize scaffold design. In particular, scaffold geometries have been optimized to avoid mechanical failure and recently also to provide a distinct mechanical stimulation to cells within the scaffold pores. This way, mechanical strain levels are optimized to favour the bone tissue formation. However, bone regeneration is a highly dynamic process where the mechanical conditions immediately after surgery might not ensure optimal regeneration throughout healing. Here, we investigated in silico whether scaffolds presenting optimal mechanical conditions for bone regeneration immediately after surgery also present an optimal design for the full regeneration process. A computer framework, combining an automatic parametric scaffold design generation with a mechano-biological bone regeneration model, was developed to predict the level of regenerated bone volume for a large range of scaffold designs and to compare it with the scaffold pore volume fraction under favourable mechanical stimuli immediately after surgery. We found that many scaffold designs could be considered as highly beneficial for bone healing immediately after surgery; however, most of them did not show optimal bone formation in later regenerative phases. This study allowed to gain a more thorough understanding of the effect of scaffold geometry changes on bone regeneration and how to maximize regenerated bone volume in the long term. Supplementary Information The online version contains supplementary material available at 10.1007/s10237-021-01472-2.

The compliance of the proximal aortic wall is a major determinant of cardiac afterload. Aortic compliance is often estimated based on cross-sectional area changes over the pulse pressure, under the assumption of a negligible longitudinal stretch during the pulse. However, the proximal aorta is subjected to significant axial stretch during cardiac contraction. In the present study, we sought to evaluate the importance of axial stretch on compliance estimation by undertaking both an in silico and an in vivo approach. In the computational analysis, we developed a 3-D finite element model of the proximal aorta and investigated the discrepancy between the actual wall compliance to the value estimated after neglecting the longitudinal stretch of the aorta. A parameter sensitivity analysis was further conducted to show how increased material stiffness and increased aortic root motion might amplify the estimation errors (discrepancies between actual and estimated distensibility ranging from − 20 to − 62%). Axial and circumferential aortic deformation during ventricular contraction was also evaluated in vivo based on MR images of the aorta of 3 healthy young volunteers. The in vivo results were in good qualitative agreement with the computational analysis (underestimation errors ranging from − 26 to − 44%, with increased errors reflecting higher aortic root displacement). Both the in silico and in vivo findings suggest that neglecting the longitudinal strain during contraction might lead to severe underestimation of local aortic compliance, particularly in the case of women who tend to have higher aortic root motion or in subjects with stiff aortas.

Pressure ulcers are localized sites of tissue damage which form due to the continuous exposure of skin and underlying soft tissues to sustained mechanical loading, by bodyweight forces or because a body site is in prolonged contact with an interfacing object. The latter is the common cause for the specific sub-class of pressure ulcers termed 'medical device-related pressure ulcers', where the injury is known to have been caused by a medical device applied for a diagnostic or therapeutic purpose. Etiological research has established three key contributors to pressure ulcer formation, namely direct cell and tissue deformation, inflammatory edema and ischemic damage which are typically activated sequentially to fuel the injury spiral. Here, we visualize and analyze the above etiological mechanism using a new cell-scale modeling framework. Specifically, we consider here the deformation-inflicted and inflammatory contributors to the damage progression in a medical device-related pressure ulcer scenario, forming under a continuous positive airway pressure ventilation mask at the microarchitecture of the nasal bridge. We demonstrate the detrimental effects of exposure to high-level continuous external strains, which causes deformation-inflicted cell damage almost immediately. This in turn induces localized edema, which exacerbates the cell-scale mechanical loading state and thereby progresses cell damage further in a nonlinear, escalating pattern. The cell-scale quantitative description of the damage cascade provided here is important not only from a basic science perspective, but also for creating awareness among clinicians as well as industry and regulators with regards to the need for improving the design of skin-contacting medical devices.

Change of relative humidity (RH) in surrounding environment can greatly affect the physical and mechanical properties of wood-based panels. Commercially produced acetylated medium density fiberboard (MDF), Medite Tricoya&reg, was used in this study to predict strength and stiffness under varying humid conditions by separating samples in parallel (//) and perpendicular (&perp, ) to the sanding directions. Thickness swelling, static moduli of elasticity (MOEstat) and rupture (MORstat), and internal bond (IB) strength were measured at three different humid conditions, i.e., dry (35% RH_, standard (65% RH) and wet (85% RH). Internal bond (IB) strength was also measured after accelerated aging test. A resonance method was used to determine dynamic modulus of elasticity (MOEdyn) at the aforementioned humid conditions. Linear regression and finite element (FE) analyses were used to predict the MDF&rsquo, s static bending behavior. Results showed that dimensional stability, MOEstat, MORstat and IB strength decreased significantly with an increase in RH. No reduction of IB strength was observed after 426 h of accelerated aging test. A multiple regression model was established using MOEdyn and RH values to predict MOEstat and MORstat. In both directions (// and &perp, ), highly significant relationships were observed. The predicted and the measured values of MOEstat and MORstat were satisfactorily related to each other, which indicated that the developed model can be effectively used for evaluating the strength and stiffness of Medite Tricoya&reg, MDF samples at any humid condition. Percent errors of two different simulation techniques (standard and extended FE method) showed highly efficient way of simulating the MDF structures with low fidelity.

Cartilage defects are common in the knee joint of active athletes and remain a problem as a strong risk factor for osteoarthritis. We hypothesized that landing during sport activities, implication for subfailure ACL loading, would generate greater contact pressures (CP) at the lateral knee compartment. The purpose of this study is to investigate tibiofemoral cartilage CP of athletes during landing. Tibiofemoral cartilage contact pressures (TCCP) under clinically relevant anterior cruciate ligament subfailure external loadings were predicted using four dynamic explicit finite element (FE) models (2 males and 2 females) of the knee. Bipedal landing from a jump for five cases of varying magnitudes of external loadings (knee abduction moment, internal tibial torque, and anterior tibial shear) followed by an impact load were simulated. Lateral TCCP from meniscus (area under meniscus) and from femur (area under femur) increased by up to 94% and %30 respectively when external loads were incorporated with impact load in all the models compared to impact-only case. In addition, FE model predicted higher CP in lateral compartment by up to 37% (11.87 MPa versus 8.67 MPa) and 52% (20.19 MPa versus 13.29 MPa) for 90% and 50% percentile models, respectively. For the same percentile populations, CPs were higher by up to 25% and 82% in smaller size models than larger size models. We showed that subfailure ACL loadings obtained from previously conducted in vivo study led to high pressures on the tibiofemoral cartilage. This knowledge is helpful in enhancing neuromuscular training for athletes to prevent cartilage damage.