Gerard A. Ateshian

New Features: Added option to "contact potential" to exclude neighbors from contact search. Added support for including CDATA sections in xml file. Added "scale" 1d-function, which simply scales the input value by a user-defined constant. Improvements: Added additional checks around potential dereferencing null pointers in contact potential. Reimplemented torsion spring on revolute joint so applied moment remains linear w.r.t. the rotation angle. Mapped values are now stored with FMT_ITEM if applicable. Updated FEBioConfig.cmake. SDKs now include FEBioConfig.cmake Added FEBioConfig.cmake, a CMake build script that can be used in plugins to find and configure the FEBio paths. Made some changes to FEBioConfig.cmake [skip ci] Added option to set verbose mode, which will print info on when callbacks are entered and exited. Bug Fixes: Using different assembly method for forces of beam domain so that reaction forces are processed correctly. Fixed bug in "parameter" plot variable when field was evaluated over multiple domains. Fixed crash when elements are initially inverted. Moved where entity references in xml reader are processed. Fixed issues with output of "contact penalty" and "contact status". (#116) Fixed initial value of E parameter in tension-only linear spring. Added checks on FEModel* constructor argument for feature classes to avoid crashing when FEModel* is null in FEBio Studio. Documentation: A new Feature Manual is available here: https://febiosoftware.github.io/febio-feature-manual/

New Features: Added option to save an FEBio configuration file file from plugin repo dialog box. A new context help menu was implemented that allows users to quickly find the online documentation of any feature in the model. (#259) Added support for exporting plot object data from Python. Added option to ignore hidden parts of mesh when calculating range of colormap. (#221) Added export button to FEBio info dialog to export json file of all FEBio modules and features. Improvements: Minor cosmetic changes were applied to the plugin repo dialog. Ensured that unavailable plugins are still listed in the plugin repo if there is a local copy. Unavailable plugins will no longer be displayed in the repo Ambient and diffuse lighting settings are now stored in the settings file. Disabled menus for viewing fibers and mat axes on post side. Added IntegrateElements and IntegrateFaces to Python post module. Added option to MMG remesher to preserve selected surface. Added error check to prevent crash when a material property is not defined. When a job file cannot be found, the user is prompted to try to locate it. (#249) Added safety checks when creating equation fields on Post side to avoid crashes. Deprecated features are not exported from FEBio info dialog. Updated plugin template and building system to use new FEBioConfig.cmake Modified how point-distance tool tracks selected nodes. Had to make change in GLView to give the active tool a chance to process pickEvent. Bug Fixes: Fixed potential crash when exporting geometry to PVO file. Restored feature that prevented selection of mesh items that are in front of the planecut. Fixed issue with volume renderer not updating images. Multiple 3D textures can now be displayed again. Fixed issue with graphics context menu being responsive on post side (where it's not visible). Beam and discrete elements now show correct coloring when colormap is active. Fixed issue that all files were added to recent file list. Streamlines plot now uses smooth legendbar again. (#258) Implemented rendering for vertical discrete legend bars (#258) Streamlines are automatically updated when parameters change. Fixed issue with face activation when evaluating face and element fields. (This was causing problems when using external Python interface.) Fixed some issues with constructing and meshing compound OCC objects. Fixed problem where recording with opengl backend did not stop. Fixed couple issues with hiding elements. Made sure that mesh colors are updated after changing colormap settings. Fixed function definition for ExportFEB and ExportVTK so they can be used by the Python interpreter. Fixed issue with transparent material when colormap is enabled. (#250) Added additional support for reading surfaces via element face indices. Fixed bug where current jobpath is empty. Added some checks to ensure the febio command line and working directory are valid for existing jobs. Modified point distance tool so that users can enter node numbers manually. Fixed issue with identifying backfacing faces. Made sure that the ambient and diffuse strength of light are passed to render engine. (#238) Made sure that generating mesh can be undone (#243) Fixed screenshot feature on high DPI displays. Documentation: Updated help feature to point to the new FEBio feature manual (https://febiosoftware.github.io/febio-feature-manual/)

Cartilage damage under loading is significantly affected by viscoelasticity. This study validates a finite deformation, nonlinear viscoelastic constitutive model for the collagen matrix of immature bovine articular cartilage, using reactive viscoelasticity. To examine the flow-independent viscoelasticity of cartilage collagen, tissue samples underwent proteoglycan (PG) digestion, losing more than 98% of their initial PG content to increase their hydraulic permeability. To verify that this PG-digestion eliminated flow-dependent viscoelasticity, PG-depleted samples were subjected to a gravitational permeation experiment, demonstrating that their hydraulic permeability, k=268 ± 152 mm4/N⋅s (n = 8), was five orders of magnitude greater than reported for untreated cartilage, confirming negligible flow-dependent viscoelasticity. Digested cartilage plugs were then subjected to unconfined compression stress relaxation (four consecutive ramp-hold profiles, each increasing the compressive strain by 10%) to fit the load response and extract material properties (RMSEfit=1.86 ± 0.61 kPa, n = 8). Successful curve-fitting served as a necessary condition for validating the model. Then, a separate unconfined compression stress-relaxation test was performed on the same samples, to 40% compressive strain at the same ramp rate. The model was able to faithfully predict this experimental response using fitted material properties (RMSEpred=3.95 ± 1.33 kPa, with 0≤ stresses ≤ 155 ± 37 kPa), providing a sufficient condition for validation in unconfined compression stress-relaxation. A computational model then showed that flow-independent viscoelasticity of cartilage collagen can enhance the stress response by ∼15% at fast strain rates, over flow-dependent effects. However, we estimate from prior studies that flow-independent viscoelasticity may enhance the stress response of cartilage by up to 200%, implying that PGs probably contribute significantly to the tissue's flow-independent viscoelasticity.

FEBio Studio version 3.0 is a major update and contains a lot of new features and changes. The two main design goals were to make working with FBS more programmable and to provide more tools for debugging FEBio runs. The following is a short summary of the most noteworthy changes in FBS3. Please see the FEBio Studio User Manual for more details. The FEBio Monitor allows users to run FEBio models interactively from the graphical user interface. The model's state can be inspected visually at any time during the solution process. FEBio Reports provide a comprehensive analysis of the FEBio job. FEBio Reports can also be generated from FEBio log files, though they may be less detailed than reports generated from FEBio jobs that are run inside FEBio Studio. FEBio Studio now supports Python. A simple Python editor is available within FBS and the built-in Python interpreter (using Python 3.13.1) can run custom Python scripts. (An external Python module is in development and will be available in the next release.) Users can now generate FEBio plugins entirely from the FEBio Studio interface. The plugin files are generated via a wizard. They can then be edited within FBS3 and build into a plugin. The new Plugin Repository provides access to FEBio plugins developed by others. Using the Plugin Repo, users can quickly find plugins and install them in their local installation. FEBio Studio's render engine has been completely overhauled and now uses a hardware abstraction layer. This means that the user can now choose what render backend to use on their system. For instance, mac users can now use Metal. Other supported backends are OpenGL (all OS), Direct3D 11/12 (Windows), and Vulkan (Windows and Linux). In addition, FBS3 now uses the .fsm extension again as the default extension for FEBio Studio models. (It can still read .fs2 files and some other older formats.) The FBS3 settings are now stored in a different location than FBS2 so FBS3 will not import the FBS2 settings. The settings are now stored in an INI file and, in principle, can be hand-edited although this is not recommended. The following lists changes in addition to the new features listed above. New Features: A ray-tracer was implemented that allows users to generate high-quality, arbitrary resolution images of their models and results. The ray-tracer will also produce better results when shadows or transparency is required. Instead of simply using colors for materials and objects, users can now customize all the visual material properties that are used to rendered the model (on build and post side). Environment maps can be configured to enable special reflection effects. Added tools to measure the average surface normal and the dihedral angle between two selected faces. Added support for angle criterion to MMG Remesh modifier. Added support for global definitions and made a few other tweaks to the Abaqus reader. Added support for triangular elements in Extrude-to-surface tool. Added support for curves in ICP Registration tool. Implemented Extrude-to-surface tool. Added color picking button on 3D Image Settings panel. Added Math Function data filter to post data panel. (#196) Added option to "Project Nodes" modifier to project nodes onto a user-specified plane. Added arithmetic filter for scalar face data. Improvements: Added templates for reporting issues through GitHub Issues. Modified moment of inertia tool to return eigenvectors and eigenvalues of the MOI tensor. Modified calculation of element volume to work with shell elements and to return area when shell thickness is zero. Removed unused toolbar button in New dialog. FEBio Studio now uses the C locale for its default when formatting numbers Surface metrics tool now reports in global coordinates. Renamed AverageNormalTool to FaceMetricsTool and added centroid calculation. Modified Purge Selections option so that log items are removed if they have selections assigned. Fixed some problems with import of springs in Abaqus file reader. Now storing nodesize to settings. Added checks for shared nodes and degenerate hexes in extrude to surface tool. Now using faster nearest-node query in ICP registration to speed things up a bit. Modified ICP Registration tool so it works with different type of selections. Modified how signed distance is calculated in distance map. Users can now choose the convention for calculating signed distances. Added support for exporting higher order elements to stl and surf. (Higher-order elements are triangulated before export.) Renamed "invert" math function filter to "negate" (#196) Added filename to RAW image import dialog. (#184) Bug Fixes: Fixed issue with reading shell thickness for element sets from feb file. Fixed bug in reading SCALARS section from vtk legacy files. Fixed issue with exporting VTK data. Fixed issue with unhiding faces of an editable surface. Updating material assignments when objects are deleted. Fixed bug in processing nodesets in Abaqus import. Fixed several issues with import of STEP and BREP files. Documentation: New FBS3 features are added to the documentation. Some images were updated to reflect the new FBS3 interface.

New Features: Added plot variable for plastic yield stress, updated nonlinear iterative solution method for reactive plasticity to produce better results for yield criterion Deshpande-Fleck Added plot variables for the Drucker shear stress, the Drucker-Prager stress criterion, and the Deshpande-Fleck stress criterion Added Deshpande-Fleck yield/damage criterion Added Drucker-Prager failure or yield criterion. Fixed factor of 2 error in tens4dmm::dyad4 calculation Added support for "const" ElementData section. Added pipette aspiration pressure load Added support for reading and writing xml encode control characters. Added support for MAT3F element data in VTK export. Added support for FMT_MULT domain variables to VTK export. These fields are stored as nodal data. Added "incremental displacement" plot variable that calculates the change in displacement from the previously stored state. Implemented fiber-pow fiber material model. Implemented fftw-based image blurring algorithm. FEBio no longer requires a config file to run. Config files must now be explicitly added to the command line (use -config). Implemented active contraction model valid for uncoupled materials. Improvements: Added body force stiffness calculation for beam domains. Updated Deshpande-Fleck yield criterion to be more consistent with the paper. Modified parameterization of FEEllipsoidalFiberDensityDistribution to simplify assigning maps. Added option to stiffness diagnostic to only test a limited number of equations. Initialized "spa" member of the "ellipsoidal" density distribution to a valid value. Some minor changes to continuous fiber framework to simplify some plugin development. Added error message when rve fails to load. Modified sign convention in "rigid joint" to be consistent with other rigid connectors. The invalid command line option is now reported to the user. Allowed some whitespace in the tag's value when defining maps. Bug Fixes: Fixed bug in FEBioMech/FEBioMechModule.cpp Fixed method for evaluating isobaric specific heat capacity in real liquids, gases and vapors Fixed minor bug to allow gap tolerance to be specified for AUGLAG in sliding-elastic, even when tol=0 Fixed crash in export of "PK1 norm" plot variable. (#111) Fixed bug in writing mat3 data to vtk file. Fixed bug in serialization of FEReaction. Fixed issue with order of serializing data. Fixed bug where nodeset was not set for nodedata generators. Fixed issue in elasticity calculation in several materials. Fixed several issues with stiffness matrices of rigid connectors. Also implemented Lagrange Multiplier method for all rigid connectors. Alpha parameters are now only set in dynamic analyses. This fixes a bug where alpha parameters affected static analyses too. Fixed problems when running micro-materials. Fixed issues with stiffness matrix of "rigid joint". Fixed issue with Gaussian filter in fftw blur. The "import" plugin folder in config file is now supported on all OSes. Fixed stiffness matrix for rigid connectors. [skip ci] Stiffness matrix now handles rigid nodes correctly. Fixed unit assignments in muscle material parameter list. Documentation: Description of FEBio tasks was added (section 2.10). The tables of plot and log variables were expanded and are now available in Appendix E. Many missing boundary conditions, initial conditions, and loads were added to the documentation. Descriptions of several domain types were updated. Documentation on FEBio's explicit solver was added to section 3.3.9. Added documentation for Deshpande-Fleck damage/yield criterion Added description of pipette aspiration pressure load. Fixed reference in active contraction material in theory manual. Updated description of time stepper in user manual. Fixed documentation of fibers-3d-fei integration rule. Updated developer's manual. Fixed some typos in the material plugin section and added a new section on creating plugins with fbs3. Updated user manual to correct numbering error for reactive viscoelastic trigger (should be 0, 1, 2 not 1, 2, 3)

Purpose: Clinical failure rates associated with in-stent restenosis are difficult to predict and manage, particularly at the patient-specific level. Studies have linked biomechanical factors to focal disease development and progression, suggesting that physics-based simulations using finite element (FE) approaches hold potential to mitigate stent failure rates. However, insufficient validation to assess the accuracy of model predictions limit model credibility for clinical translation. Herein, we established a computational framework to validate vascular stent deployment by integrating robust simulation and rigorous experimental approaches. Methods: Experimental testing characterized the transient deformation of a commercially available balloon-expandable stent system, and high-resolution image data were post-processed to create a representative FE model. Nonlinear material behaviors and physical boundary conditions were varied to create mixed-fidelity models that assessed the effects of modeling assumptions on stent deformation metrics. Results: Qualitative comparisons of stent deployment stages showed that high-fidelity FE models captured the characteristic burst opening of the stent edges, followed by the central stent region. Quantitative metrics determined from pressure-diameter curves showed strong agreement, with root mean square error and concordance correlation coefficient values for the proximal, central, and distal diameters ranging from 0.31 mm and 0.96, respectively (lowest fidelity) to 0.21 mm and 0.99 (highest fidelity). Analysis of higher-order metrics (i.e., dog-boning, foreshortening) further demonstrated strong agreement. Conclusion: This framework successfully established a validation plan for vascular stent deployment, analyzed errors in model development, and demonstrated the utility of quantitative assessments, potentially improving the translatability of in silico tools and reducing device failure rates.

This article reviews our current state of knowledge about friction, lubrication and wear of articular cartilage in diarthrodial joints, in relation to osteoarthritis. The main conclusion from this review is that the primary functional role of synovial fluid is to reduce the propensity of articular cartilage against wear from cyclical compression, not cyclical friction, though they are concurrent during normal joint motion. Contrary to widespread concepts about the role of synovial fluid, its primary function is not to reduce the friction coefficient of cartilage against cartilage, which is already very low when tested in physiological buffered saline. Instead, evidence presented from our recent studies demonstrates that synovial fluid delays the onset of delamination damage under reciprocating compressive contact, and that this mechanism depends on the concentration of synovial fluid. Therefore, it appears that some molecular constituent(s) of synovial fluid is (are) responsible for this protective effect. Identifying this (these) constituent(s), which must be able to rapidly transport (in a matter of minutes) into the top few hundreds of microns from the articular surface to impart their protective effect to the middle zone of cartilage, may become an important objective of future investigations. These findings may alter our understanding of the mechanical factors that might lead to the onset of osteoarthritis, by placing a greater emphasis on the synthesis and concentration of these molecular constituents in situ.

The uterine cervix is a soft biological tissue with critical biomechanical functions in pregnancy. It is a mechanical barrier that supports the growing fetus. As pregnancy progresses, the cervix becomes more compliant and eventually opens in late pregnancy to facilitate childbirth. This dual function is facilitated by extensive remodeling of the cervical extracellular matrix (ECM), giving rise to its complex time-dependent material properties. Premature cervical remodeling is known to result in preterm birth, defined as birth before 37 weeks of gestation. While previous work has studied cervical remodeling using various biomechanical methods, it remains unclear how the intrinsic or flow-independent viscoelastic behavior of the cervix is influenced by cervical remodeling. In this study, an anisotropic reactive viscoelastic material model was formulated and investigated under tensile deformation to understand material behavior in cervical remodeling. To calibrate the model, experimental force relaxation data was used from uniaxial tension tests on Rhesus macaque cervical specimens from four gestational time points. The results showed that cervical tissue equilibrium and instantaneous stiffness significantly decreased from the nonpregnant (NP) to the late pregnancy status. In addition, cervical tissue in the late third trimester relaxed faster to equilibrium than the other gestational groups, particularly at prescribed grip-to-grip strains greater than 30%. This fast relaxation to equilibrium helps the cervix dissipate tensile hoop stresses induced by the fetus during labor, preventing its rupture. This work provides insights into time-dependent cervical remodeling features, which are crucial for developing diagnostic methods and treatments for preterm birth.

In this study, we address fundamental theoretical considerations that should guide biomedical engineers in the assessment of patient-specific risk of tissue failure, or the assessment of other material properties needed for patient-specific computational modeling, based on noninvasive imaging modalities. Upon reviewing theoretical concepts of mechanics, the primary conclusion is that patient-specific material properties, such as measures of tissue failure, cannot be observed directly, because material properties are dependent on nonobservable functions of state. However, since functions of state may be formulated to depend on observable state variables, and since noninvasive imaging may be used to assess such variables, it behooves investigators to find strong correlations in vitro between the material property of interest and relevant observable state variables, such as measures of tissue morphology, transport characteristics, and composition. Once such univariate or multivariate correlations have been established experimentally in vitro, the next challenge is to relate imaging-based observable measures, acquired noninvasively (e.g., in vivo), to relevant material properties such as failure criteria. The uncertainty associated with these observation-derived material properties is, at best, equal to the uncertainty of the in vitro correlation.

The uterine cervix is a soft biological tissue with critical biomechanical functions in pregnancy. It is a mechanical barrier that supports the growing fetus. As pregnancy progresses, the cervix becomes more compliant and eventually opens in late pregnancy to facilitate childbirth. This dual function is facilitated by extensive remodeling of the cervical extracellular matrix (ECM), giving rise to its complex time-dependent material properties. Premature cervical remodeling is known to result in preterm birth, defined as birth before 37 weeks of gestation. While previous work has studied cervical remodeling using various biomechanical methods, it remains unclear how the intrinsic or flow-independent viscoelastic behavior of the cervix is influenced by cervical remodeling. In this study, an anisotropic reactive viscoelastic material model was formulated and investigated under tensile deformation to understand material behavior in cervical remodeling. To calibrate the model, experimental force relaxation data was used from uniaxial tension tests on Rhesus macaque cervical specimens from four gestational time points. The results showed that cervical tissue equilibrium and instantaneous stiffness significantly decreased from the non-pregnant to the late pregnancy status. In addition, cervical tissue in the late third trimester relaxed faster to equilibrium than the other gestational groups, particularly at prescribed tensile strains greater than 30%. This fast relaxation to equilibrium helps the cervix dissipate tensile hoop stresses induced by the fetus during labor, preventing its rupture. This work provides insights into time-dependent cervical remodeling features, which are crucial for developing diagnostic methods and treatments for preterm birth.

In this 12-month long, preclinical large animal study using a canine model, we report that engineered osteochondral grafts (comprised of allogeneic chondrocyte-seeded hydrogels with the capacity for sustained release of the corticosteroid dexamethasone [DEX], cultured to functional mechanical properties, and incorporated over porous titanium bases), can successfully repair damaged cartilage. DEX release from within engineered cartilage was hypothesized to improve initial cartilage repair by modulating the local inflammatory environment, which was also associated with suppressed degenerative changes exhibited by menisci and synovium. We note that not all histological and clinical outcomes at an intermediary time point of three months paralleled 12-month outcomes, which emphasizes the importance of in vivo studies in valid preclinical models that incorporate clinically relevant follow-up durations. Together, our study demonstrates that engineered cartilage fabricated under the conditions reported herein can repair full-thickness cartilage defects and promote synovial joint health and function.

Interstitial fluid load support (FLS) is a dominant mechanism of lubrication in cartilage, producing a low friction coefficient while enhancing the tissue’s load bearing capabilities. Due to its viscosity, synovial fluid (SF) may retard loss of FLS by slowing the exudation of interstitial fluid from the cartilage. This study tested this hypothesis by comparing the stress-relaxation (SRL) response of immature bovine articular cartilage immersed either in phosphate buffered saline (PBS) or in healthy mature bovine SF, under unconfined compression (fluid exudation across cut lateral tissue boundary) and indentation testing (fluid exudation across articular surface). To investigate the influence of diffusion of SF molecular constituents into cartilage, the effect of incubation time in SF on SRL was also investigated. The SRL response in unconfined compression was not significantly different in PBS versus SF when compared directly (p=0.98) and had a slope of m=1.00 ± 0.04 (R2=0.989 ± 0.007). Samples tested in PBS exhibited characteristic relaxation times, τPBS=42.6 ± 5.3 s and τSF=40.8 ± 4.7 s, that were not significantly different (p=0.40). Incubation time of 24 hours in SF resulted in no significant difference in the SRL response (p=0.39, m=1.03 ± 0.12; R2=0.983 ± 0.011, and τPBS=43.4 ± 10.7 s versus τSF=41.5 ± 4.8 s, p=0.59). Indentation testing showed some statistically significant, but functionally insignificant, difference in SRL responses in PBS versus SF with a slope of m=0.958 ± 0.060 (R2=0.957 ± 0.020, p=0.029, and τPBS=16.9 ± 2.6 s versus τSF =19.4 ± 3.3 s, p=0.073). Based on these results, we reject the hypothesis that healthy SF can retard the loss of FLS in cartilage due to its viscosity.

Objective: Based on our recent study, which showed that cartilage fatigue failure in reciprocating sliding contact results from cyclical compressive forces, not from cyclical frictional forces, we hypothesize that a major functional role for synovial fluid (SF) is to reduce the rate of articular cartilage fatigue failure from cyclical compressive loading. Design: The rate of cartilage fatigue failure due to repetitive compressive loading was measured by sliding a glass lens against an immature bovine cartilage tibial plateau strip immersed in mature bovine SF, phosphate-buffered saline (PBS), or SF/PBS dilutions (50% SF and 25% SF; n=8 for all four bath conditions). After 24 hours of reciprocating sliding (5,400 cycles), samples were visually assessed and if damage was observed, the test was terminated; otherwise, testing was continued for 72 hours (16,200 cycles), with solution refreshed daily. Results: All eight samples in the PBS group exhibited physical damage after 24 hours, with an average final surface roughness of Rq=0.210±0.067mm. The SF group showed no damage after 24 hours; however, two of eight samples became damaged after 72 hours, producing a significantly lower average surface roughness than the PBS group Rq=0.059±0.030mm;p<10−4). For the remaining groups, at 72 hours one of eight samples damaged in the 50% SF group, and five of eight samples damaged in the 25% SF group. Conclusions: The results strongly support our hypothesis, showing that decreased amounts of SF in the testing bath produces increased rates of fatigue failure in cartilage that was subjected to reciprocating sliding contact.

Fatigue failure in biological soft tissues plays a critical role in the etiology of chronic soft tissue injuries and diseases such as osteoarthritis (OA). Understanding failure mechanisms is hindered by the decades-long timescales over which damage takes place. Analyzing the factors contributing to fatigue failure requires the help of validated computational models developed for soft tissues. This study presents a framework for fatigue failure of fibrous biological tissues based on reaction kinetics, where the composition of intact and fatigued material regions can evolve via degradation and breakage over time, in response to energy-based fatigue and damage criteria. Using reactive constrained mixture theory, material region mass fractions are governed by the axiom of mass balance. Progression of fatigue is controlled by an energy-based reaction rate, with user-selected probability functions defining the damage propensity of intact and fatigued material regions. Verification of this reactive theory, which is implemented in the open-source FEBio finite element software, is provided in this study. Validation is also demonstrated against experimental data, showing that predicted damage can be linked to results from biochemical assays. The framework is also applied to study fatigue failure during frictional contact of cartilage. Simulating previous experiments suggests that frictional effects slightly increase fatigue progression, but the main driver is cyclic compressive contact loading. This study demonstrated the ability of theoretical models to complement and extend experimental findings, advancing our understanding of the time progression of fatigue in biological tissues.

The synovium plays a crucial role in diarthrodial joint health, and its study has garnered appreciation as synovitis has been linked to osteoarthritis symptoms and progression. Quantitative synovium structure–function data, however, remain sparse. In the present study, we hypothesized that tissue glycosaminoglycan (GAG) content contributes to the low friction properties of the synovium. Bovine and human synovium tribological properties were evaluated using a custom friction testing device in two different cases: (1) proteoglycan depletion to isolate the influence of tissue GAGs in the synovium friction response and (2) interleukin-1 (IL) treatment to observe inflammation-induced structural and functional changes. Following proteoglycan depletion, synovium friction coefficients increased while GAG content decreased. Conversely, synovium explants treated with the proinflammatory cytokine IL exhibited elevated GAG concentrations and decreased friction coefficients. For the first time, a relationship between synovium friction coefficient and GAG concentration is demonstrated. The study of synovium tribology is necessary to fully understand the mechanical environment of the healthy and diseased joint.

Recurrent bleeding in the synovial joint, such as the knee, can give rise to chronic synovitis and degenerative arthritis, which are major causes of morbidity. Whereas chronic arthropathy affects one-fifth of hemophiliacs, conditions such as rheumatoid arthritis (RA), periarticular and articular fractures, osteochondral autograft transplantation surgery, and anterior cruciate ligament (ACL) injury are also associated with joint bleeding. Synovial joint trauma is associated with inflammation, acute pain, bloody joint effusion, and knee instability. Clinically, some physicians have advocated for blood aspiration from the joint post-injury to mitigate the harmful effects of bleeding. Despite the significant potential clinical impact of joint bleeding, the mechanism(s) by which joint bleeding, acute or microbleeds, leads to deleterious changes to the synovial joint remains understudied. This review will address the impact of blood on synovial joint tissues observed from in vitro and in vivo studies. While the deleterious effects of blood on cartilage and synovium are well-described, there are much fewer reports describing the negative effects of blood on the meniscus, cruciate ligaments, and subchondral bone. Based on our studies of blood in co-culture with chondrocytes/cartilage, we raise the possibility that ferroptosis, an iron-dependent, nonapoptotic form of regulated cell death, plays a contributing role in mediating hemophilic arthropathy (HA) and may represent a therapeutic target in reducing the negative impact of joint bleeds.

Objectives: In presence of cam-type femoroacetabular impingement syndrome (FAIS), secondary labral tears are common and can disrupt the functions of the acetabular labrum, leaving the articular cartilage vulnerable to potential accelerated degeneration. Currently, significant controversy exists regarding the indications for repair, reconstruction, and augmentation of the labrum. While others have suggested that labral reconstruction should be utilized in the setting of the ossified labrum, severely damaged labrum, irreparable labrum, and severe labral deficiency, others have suggested that indications should be expanded to include hypotrophic (&lt; 3mm) or hypertrophic labra. Despite the fact that surgical techniques have already been developed to address the hypotrophic and hypertrophic labrum, the role of labral size in chondrolabral and femoroacetabular biomechanics is currently unknown. Therefore, the objective of this study was to assess the influence of labral size on the mechanical environment of the cam-type hip during walking and squatting using finite element (FE) modeling. We hypothesized that a variation in labral size will not further alter the already deleterious contact stresses and strains in cam-type hips, therefore mechanical indices reflecting the likelihood of cartilage damage would be unchanged. Methods: For our FE models, we adapted closed bounded surfaces of the bones, cartilage, and labrum segmented from CT image data of a volunteer with cam-type FAIS with an alpha angle of 78°. Three clinical morphologies were considered in the simulations: (1) anatomically normal labrum, corresponding to the segmented geometry; (2) a hypotrophic labrum (width ≤ 3mm); (3) a hypertrophic labrum (width ≥ 6mm). The width of the labrum was defined as the distance from the chondrolabral junction to the apex of the labrum (Fig. 1). The labrum, cartilage, and pelvis surfaces were discretized using quadratic tetrahedral elements in the ANSA software package (BETA CAE Systems SA). Cartilage layers were represented as anisotropic hyperelastic materials with tension-only collagen fibers that varied in primary orientation through the thickness of the cartilage, reflecting the physiological distribution in articular cartilage. The labrum was modeled as a transversely isotropic material with collagen fibers oriented circumferentially along the acetabular rim. The modulus of the pelvis was assigned to the FE mesh based on the CT image data intensity through an established relationship between CT scanner pixel intensity and calcium equivalent density. Patient-specific kinematics from skin-marker motion tracking during gait and squat were combined with joint reaction forces collected by Bergmann et al. to provide kinematic and force boundary conditions for the FE models. All models were analyzed in FEBio ( www.febio.org ). Labral load support and the labrum fiber strain were evaluated for each morphology. Additionally, the maximum contact pressure and first principal Lagrange strain on the articular surface, and maximum shear stress on the osteochondral surface were evaluated. All outcomes were analyzed at heel-strike for gait and deep flexion for the squat. Results: A larger labrum resulted in greater load transferred to the labrum during heel-strike of the gait cycle and during deep flexion of the squat. For both activities, labral load support was the greatest for the hypertrophic labrum compared to the hypotrophic and normotrophic labra (Fig. 2). The maximum circumferential labrum fiber strain varied from 11.0% to 12.6% at heel-strike, and between 7.0% to 7.5% during deep flexion across the three models. Despite differences in labral load support, there were no measurable changes in contact pressure between the three cases during heel-strike or deep flexion (Fig. 3). The first principal Lagrange strain at heel-strike reached a maximum of 28.3% in the normotrophic labrum model, with similar levels in the hypotrophic (28.5%) and hypertrophic (27.4%) labrum models, primarily located in the anterosuperior portion of the acetabular cartilage. There was minimal variation in the first principal Lagrange strain between labrum morphologies during deep flexion, with maximum strain values ranging from 25.3% to 25.6%. Peak maximum shear stress during gait showed minimal differences across all three modeling cases, and slightly increased during deep flexion compared to heel-strike (Fig. 4). Conclusions: The variance in labral load support between hypertrophic and hypotrophic morphologies suggests that labral size affects load distribution during walking and squatting, consistent with previous findings in dysplastic hips showing larger labra correlating with increased labral load support. Despite the differences in load transmission between the three labral morphologies, the contact pressure and first principal Lagrange strain across the articular cartilage was minimally affected, and were within similar ranges previously reported for cam-type hips. Similarly, the variation in maximum shear stress was minimal between the three cases, and was above the reported magnitude of shear stress within normal hips. These findings indicate that the mechanical loading on the acetabular cartilage in cam-type hips is left unchanged regardless of labral size during walking and deep flexion, suggesting similar levels of susceptibility to cartilage damage. In the context of clinical interventions, these results have important implications for clinical decision making during primary arthroscopic surgery for cam-type FAIS, particularly regarding management of the labrum. While additional clinical studies are warranted, labral reconstruction may be unnecessary during FAIS surgery, as repair using native fibers could potentially suffice to restore hip functionality, irrespective of labral morphology. [Figure: see text][Figure: see text][Figure: see text][Figure: see text]

Thermodynamics is a fundamental topic of continuum mechanics and biomechanics, with a wide range of applications to physiological and biological processes. This study addresses two fundamental limitations of current thermodynamic treatments. First, thermodynamics tables distributed online by the U.S. National Institute of Standards and Technology (NIST) report properties of fluids as a function of absolute temperature T and absolute pressure P. These properties include mass density ρ, specific internal energy u, enthalpy h=u+P/ρ, and entropy s. However, formulations of jump conditions across phase boundaries derived from Newton's second law of motion and the first law of thermodynamics employ the gauge pressure p=P-Pr, where Pr is an arbitrarily selected referential absolute pressure. Interchanging p with P is not innocuous as it alters tabulated NIST values for u while keeping h and s unchanged. Using p for functions of state and governing equations solves the problem with using NIST entries for the specific internal energy u in standard thermodynamics tables and analyses of phase transformation in continuum mechanics. Second, constitutive models for the free energy of fluids, such as water and air, are not typically provided in standard thermodynamics treatments. This study proposes a set of constitutive models and validates them against suitably modified NIST data.

In this erratum, we correct a mistake in a subcomponent of the numerical algorithm proposed in our recent study for modeling anisotropic reactive nonlinear viscoelasticity (doi:10.1115/1.4054983), for the special case where multiple weak bond families may be recruited with loading. This correction overcomes a nonphysical response noted under uni-axial cyclical loading.

The objective of this study was to investigate whether the two most common growth mechanics modeling frameworks, the constrained-mixture growth model and the kinematic growth model, could be reconciled mathematically. The purpose of this effort was to provide practical guidelines for potential users of these modeling frameworks. Results showed that the kinematic growth model is mathematically consistent with a special form of the constrained-mixture growth model, where only one generation of a growing solid exists at any given time, overturning its entire solid mass at each instant of growth in order to adopt the reference configuration dictated by the growth deformation. The thermodynamics of the kinematic growth model, along with the specialized constrained-mixture growth model, requires a cellular supply of chemical energy to allow deposition of solid mass under a stressed state. A back-of-the-envelope calculation shows that the amount of chemical energy required to sustain biological growth under these models is negligibly small, when compared to the amount of energy normally consumed daily by the human body. In conclusion, this study successfully reconciled the two most popular growth theories for biological growth and explained the special circumstances under which the constrained-mixture growth model reduces to the kinematic growth model.

Extracellular matrix (ECM) collagen density and fibril anisotropy are thought to affect the development of new vasculatures during pathologic and homeostatic angiogenesis. Computational simulation is emerging as a tool to investigate the role of matrix structural configurations on cell guidance. However, prior computational models have only considered the orientation of collagen as a model input. Recent experimental evidence indicates that cell guidance is simultaneously influenced by the direction and intensity of alignment (i.e., degree of anisotropy) as well as the local collagen density. The objective of this study was to explore the role of ECM collagen anisotropy and density during sprouting angiogenesis through simulation in the AngioFE and FEBio modeling frameworks. AngioFE is a plugin for FEBio (Finite Elements for Biomechanics) that simulates cell-matrix interactions during sprouting angiogenesis. We extended AngioFE to represent ECM collagen as deformable 3D ellipsoidal fibril distributions (EFDs). The rate and direction of microvessel growth were modified to depend simultaneously on the ECM collagen anisotropy (orientation and degree of anisotropy) and density. The sensitivity of growing neovessels to these stimuli was adjusted so that AngioFE could reproduce the growth and guidance observed in experiments where microvessels were cultured in collagen gels of varying anisotropy and density. We then compared outcomes from simulations using EFDs to simulations that used AngioFE's prior vector field representation of collagen anisotropy. We found that EFD simulations were more accurate than vector field simulations in predicting experimentally observed microvessel guidance. Predictive simulations demonstrated the ability of anisotropy gradients to recruit microvessels across short and long distances relevant to wound healing. Further, simulations predicted that collagen alignment could enable microvessels to overcome dense tissue interfaces such as tumor-associated collagen structures (TACS) found in desmoplasia and tumor-stroma interfaces. This approach can be generalized to other mechanobiological relationships during cell guidance phenomena in computational settings.

SUMMARY Objective: Wear of articular cartilage is not well understood. We hypothesize that cartilage wears due to fatigue failure in repetitive compression instead of reciprocating friction. Design: This study compares reciprocating sliding of immature bovine articular cartilage against glass in two testing configurations: (1) a stationary contact area configuration (SCA), which results in static compression, interstitial fluid depressurization, and increasing friction coefficient during reciprocating sliding, and (2) a migrating contact area configuration (MCA), which maintains pressurization and low friction while producing repetitive compressive loading in addition to reciprocating sliding. Contact pressure, sliding duration, and sliding distance were controlled to be similar between test groups. Results: SCA tests exhibited an average friction coefficient of μ = 0.084 ± 0.032, while MCA tests exhibited a lower average friction coefficient of μ = 0.020 ± 0.008 (p < 10−4). Despite the lower friction, MCA cartilage samples exhibited clear surface damage with a significantly greater average surface deviation from a fitted plane after wear testing (Rq = 0.125 ± 0.095 mm) than cartilage samples slid in a SCA configuration (Rq = 0.044 ± 0.017 mm, p = 0.002), which showed minimal signs of wear. Polarized light microscopy confirmed that delamination damage occurred between the superficial and middle zones of the articular cartilage in MCA samples. Conclusions: The greatest wear was observed in the group with lowest friction coefficient, subjected to cyclical instead of static compression, implying that friction is not the primary driver of cartilage wear. Delamination between superficial and middle zones implies the main mode of wear is fatigue failure under cyclical compression, not fatigue or abrasion due to reciprocating frictional sliding.

The objective of this study was to implement a novel fluid-solutes solver into the open-source finite element software FEBio, that extended available modeling capabilities for biological fluids and fluid-solute mixtures. Using a reactive mixture framework, this solver accommodates diffusion, convection, chemical reactions, electrical charge effects, and external body forces, without requiring stabilization methods that were deemed necessary in previous computational implementations of the convection-diffusion-reaction equation at high Peclet numbers. Verification and validation problems demonstrated the ability of this solver to produce solutions for Peclet numbers as high as 1011, spanning the range of physiological conditions for convection-dominated solute transport. This outcome was facilitated by the use of a formulation that accommodates realistic values for solvent compressibility, and by expressing the solute mass balance such that it properly captured convective transport by the solvent and produced a natural boundary condition of zero diffusive solute flux at outflow boundaries. Since this numerical scheme was not necessarily foolproof, guidelines were included to achieve better outcomes that minimize or eliminate the potential occurrence of numerical artifacts. The fluid-solutes solver presented in this study represents an important and novel advancement in the modeling capabilities for biomechanics and biophysics as it allows modeling of mechanobiological processes via the incorporation of chemical reactions involving neutral or charged solutes within dynamic fluid flow. The incorporation of charged solutes in a reactive framework represents a significant novelty of this solver. This framework also applies to a broader range of nonbiological applications.

This study reviews the progression of our research, from modeling growth theories for cartilage tissue engineering, to the formulation of constrained reactive mixture theories to model inelastic responses in any solid material, such as theories for damage mechanics, viscoelasticity, plasticity, and elasto-plastic damage. In this framework, multiple solid generations α can co-exist at any given time in the mixture. The oldest generation is denoted by α=s and is called the master generation, whose reference configuration Xs is observable. The solid generations α are all constrained to share the same velocity vs, but may have distinct reference configurations Xα. An important element of this formulation is that the time-invariant mapping Fαs=∂Xα/∂Xs between these reference configurations is a function of state, whose mathematical formulation is postulated by constitutive assumption. Thus, reference configurations Xα are not observable (α≠s). This formulation employs only observable state variables, such as the deformation gradient Fs of the master generation and the referential mass concentrations ρrα of each generation, in contrast to classical formulations of inelastic responses which rely on internal state variable theory, requiring evolution equations for those hidden variables. In constrained reactive mixtures, the evolution of the mass concentrations is governed by the axiom of mass balance, using constitutive models for the mass supply densities ρˆrα. Classical and constrained reactive mixture approaches share considerable mathematical analogies, as they both introduce a multiplicative decomposition of the deformation gradient, also requiring evolution equations to track some of the state variables. However, they also differ at a fundamental level, since one adopts only observable state variables while the other introduces hidden state variables. In summary, this review presents an alternative foundational approach to the modeling of inelastic responses in solids, grounded in the classical framework of mixture theory.

Renal cystogenesis is the pathological hallmark of autosomal dominant polycystic kidney disease, caused by PKD1 and PKD2 mutations. The formation of renal cysts is a common manifestation in ciliopathies, a group of syndromic disorders caused by mutation of proteins involved in the assembly and function of the primary cilium. Cystogenesis is caused by the derailment of the renal tubular architecture and tissue deformation that eventually leads to the impairment of kidney function. However, the biomechanical imbalance of cytoskeletal forces that are altered in cells with Pkd1 mutations has never been investigated, and its nature and extent remain unknown. In this computational study, we explored the feasibility of various biomechanical drivers of renal cystogenesis by examining several hypothetical mechanisms that may promote morphogenetic markers of cystogenesis. Our objective was to provide physics-based guidance for our formulation of hypotheses and our design of experimental studies investigating the role of biomechanical disequilibrium in cystogenesis. We employed the finite element method to explore the role of (1) wild-type versus mutant cell elastic modulus; (2) contractile stress magnitude in mutant cells; (3) localization and orientation of contractile stress in mutant cells; and (4) sequence of cell contraction and cell proliferation. Our objective was to identify the factors that produce the characteristic tubular cystic growth. Results showed that cystogenesis occurred only when mutant cells contracted along the apical-basal axis, followed or accompanied by cell proliferation, as long as mutant cells had comparable or lower elastic modulus than wild-type cells, with their contractile stresses being significantly greater than their modulus. Results of these simulations allow us to focus future in vitro and in vivo experimental studies on these factors, helping us formulate physics-based hypotheses for renal tubule cystogenesis.

Vulnerable plaques associated with softer components may rupture, releasing thrombotic emboli to smaller vessels in the brain, thus causing an ischemic stroke. Pulse Wave Imaging (PWI) is an ultrasound-based method that allows for pulse wave visualization while the regional pulse wave velocity (PWV) is mapped along the arterial wall to infer the underlying wall compliance. One potential application of PWI is the non-invasive estimation of plaque’s mechanical properties for investigating its vulnerability. In this study, the accuracy of PWV estimation in stenotic vessels was investigated by computational simulation and PWI in validation phantoms to evaluate this modality for assessing future stroke risk. Polyvinyl alcohol (PVA) phantoms with plaque constituents of different stiffnesses were designed and constructed to emulate stenotic arteries in the experiment, and the novel fabrication process was described. Finite-element fluid-structure interaction simulations were performed in a stenotic phantom model that matched the geometry and parameters of the experiment in phantoms. The peak distension acceleration of the phantom wall was tracked to estimate PWV. PWVs of 2.57 ms−1, 3.41 ms−1, and 4.48 ms−1 were respectively obtained in the soft, intermediate, and stiff plaque material in phantoms during the experiment using PWI. PWVs of 2.10 ms−1, 3.33 ms−1, and 4.02 ms−1 were respectively found in the soft, intermediate, and stiff plaque material in the computational simulation. These results demonstrate that PWI can effectively distinguish the mechanical properties of plaque in phantoms as compared to computational simulation.

Cartilage repair has been studied extensively in the context of injury and disease, but the joint's management of regular sub-injurious damage to cartilage, or 'wear and tear,' which occurs due to normal activity, is poorly understood. We hypothesize that this cartilage maintenance is mediated in part by cells derived from the synovium that migrate to the worn articular surface. Here, we demonstrate in vitro that the early steps required for such a process can occur. First, we show that under physiologic mechanical loads, chondrocyte death occurs in the cartilage superficial zone along with changes to the cartilage surface topography. Second, we show that synoviocytes are released from the synovial lining under physiologic loads and attach to worn cartilage. Third, we show that synoviocytes parachuted onto a simulated or native cartilage surface will modify their behavior. Specifically, we show that synoviocyte interactions with chondrocytes lead to changes in synoviocyte mechanosensitivity, and we demonstrate that cartilage-attached synoviocytes can express COL2A1, a hallmark of the chondrogenic phenotype. Our findings suggest that synoviocyte-mediated repair of cartilage 'wear and tear' as a component of joint homeostasis is feasible and is deserving of future study.