Biomechanical characterisation of ovine spinal facet joint cartilage

The spinal facet joints are known to be an important component in the kinematics and the load transmission of the spine. The articular cartilage in the facet joint is prone to degenerative changes which lead to back pain and treatments for the condition have had limited long term success. There is currently a lack of information on the basic biomechanical properties of the facet joint cartilage which is needed to develop tissue substitution or regenerative interventions. In the present study, the thickness and biphasic properties of ovine facet cartilage were determined using a combination of indentation tests and computational modelling. The equilibrium biphasic Young's modulus and permeability were derived to be 0.76±0.35 MPa and 1.61±1.10×10^?15 m⁴/(Ns) respectively, which were within the range of cartilage properties characterised from the human synovial joints. The average thickness of the ovine facet cartilage was 0.52±0.10 mm, which was measured using a needle indentation test. These properties could potentially be used for the development of substitution or tissue engineering interventions and for computational modelling of the facet joint. Furthermore, the developed method to characterise the facet cartilage could be used for other animals or human donors.     

Finite element lumbar spine facet contact parameter predictions are affected by the cartilage thickness distribution and initial joint gap size

Current finite element modeling techniques utilize geometrically inaccurate cartilage distribution representations in the lumbar spine. We hypothesize that this shortcoming severely limits the predictive fidelity of these simulations. Specifically, it is unclear how these anatomically inaccurate cartilage representations alter range of motion and facet contact predictions. In the current study, cadaveric vertebrae were serially sectioned, and images were taken of each slice in order to identify the osteochondral interface and the articulating surface. A series of custom-written algorithms were utilized in order to quantify each facet joint's three-dimensional cartilage distribution using a previously developed methodology. These vertebrae-dependent thickness cartilage distributions were implemented on an L1 through L5 lumbar spine finite element model. Moments were applied in three principal planes of motion, and range of motion and facet contact predictions from the variable thickness and constant thickness distribution models were determined. Initial facet gap thickness dimensions were also parameterized. The data indicate that the mean and maximum cartilage thickness increased inferiorly from L1 to L5, with an overall mean thickness value of 0.57 mm. Cartilage distribution and initial facet joint gap thickness had little influence on the lumbar range of motion in any direction, whereas the mean contact pressure, total contact force, and total contact area predictions were altered considerably. The data indicate that range of motion predictions alone are insufficient to establish model validation intended to predict mechanical contact parameters. These data also emphasize the need for the careful consideration of the initial facet joint gap thickness with respect to the spinal condition being studied.     

Spinal facet joint biomechanics and mechanotransduction in normal, injury and degenerative conditions

The facet joint is a crucial anatomic region of the spine owing to its biomechanical role in facilitating articulation of the vertebrae of the spinal column. It is a diarthrodial joint with opposing articular cartilage surfaces that provide a low friction environment and a ligamentous capsule that encloses the joint space. Together with the disc, the bilateral facet joints transfer loads and guide and constrain motions in the spine due to their geometry and mechanical function. Although a great deal of research has focused on defining the biomechanics of the spine and the form and function of the disc, the facet joint has only recently become the focus of experimental, computational and clinical studies. This mechanical behavior ensures the normal health and function of the spine during physiologic loading but can also lead to its dysfunction when the tissues of the facet joint are altered either by injury, degeneration or as a result of surgical modification of the spine. The anatomical, biomechanical and physiological characteristics of the facet joints in the cervical and lumbar spines have become the focus of increased attention recently with the advent of surgical procedures of the spine, such as disc repair and replacement, which may impact facet responses. Accordingly, this review summarizes the relevant anatomy and biomechanics of the facet joint and the individual tissues that comprise it. In order to better understand the physiological implications of tissue loading in all conditions, a review of mechanotransduction pathways in the cartilage, ligament and bone is also presented ranging from the tissue-level scale to cellular modifications. With this context, experimental studies are summarized as they relate to the most common modifications that alter the biomechanics and health of the spine-injury and degeneration. In addition, many computational and finite element models have been developed that enable more-detailed and specific investigations of the facet joint and its tissues than are provided by experimental approaches and also that expand their utility for the field of biomechanics. These are also reviewed to provide a more complete summary of the current knowledge of facet joint mechanics. Overall, the goal of this review is to present a comprehensive review of the breadth and depth of knowledge regarding the mechanical and adaptive responses of the facet joint and its tissues across a variety of relevant size scales.     

A model of anterior cruciate ligament reconstructive surgery: A validation construct and computational insights

This study sought to develop a computational framework that emulates the anterior cruciate ligament reconstruction surgery using transtibial portal technique. The proposed model included the tibia–femoral and patella–femoral joints, articular cartilage and menisci. Key surgical parameters were incorporated including bone-patellar-tendon-bone graft excision and pre-tensioning, tunnel morphology, bone plugs, and bone plug fixation. Several simulation steps were parameterized to reflect the clinically reported surgical procedure. Our focus was to explore the intra-operative effects of variations in tunnel directions on the selected metrics of joint mechanics during Lachman and Anterior Drawer tests. A mathematical construct capable of transforming the limited and heterogeneous experimental and surgical data to evidence-based validation was adopted to ensure the viability of the finite element models. We found that the proposed models, subject to a variation in tunnel directions, resulted in simulation outputs that favor the reported experimental data of Lachman and Anterior Drawer tests under uncertainty. Simulation results for a population of three-dimensional tunnel orientations provided insights into the graft–tunnel contact mechanics and the spatial stress distribution in the graft, insights that have been anecdotally observed in prior experimental studies. The intraarticular graft tension was found to be higher than the estimated in tunnel graft force, and larger differences were found for the least inclined tunnels exhibiting higher contact pressures, transverse bending and twisting of the graft and Von-Mises stress at the graft–femoral tunnel interface. Conversely, tunnels with high inclination angles exhibited higher intraarticular graft tension and Von-Mises stress at the graft–tibial bone plug interface.     

Accomplishments in genome-scale in silico modeling for industrial and medical biotechnology

Driven by advancements in high-throughput biological technologies and the growing number of sequenced genomes, the construction of in silico models at the genome scale has provided powerful tools to investigate a vast array of biological systems and applications. Here, we review comprehensively the uses of such models in industrial and medical biotechnology, including biofuel generation, food production, and drug development. While the use of in silico models is still in its early stages for delivering to industry, significant initial successes have been achieved. For the cases presented here, genome-scale models predict engineering strategies to enhance properties of interest in an organism or to inhibit harmful mechanisms of pathogens. Going forward, genome-scale in silico models promise to extend their application and analysis scope to become a transformative tool in biotechnology.     

A Mathematical Formulation for 3D Quasi-Static Multibody Models of Diarthrodial Joints

This study describes a genera] set of equations for quasi-static analysis of three-dimensional multibody systems, with a particular emphasis on modeling of diarthrodial joints. The model includes articular contact, muscle forces, tendons and tendon pulleys, ligaments, and the wrapping of soft tissue structures around bone and cartilage surfaces. The general set of equations governing this problem are derived using a consistent notation for all types of links, which can be converted conveniently into efficient computer codes. The computational efficiency of the model is enhanced by the use of analytical Jacobians, particularly in the analysis of articular surface contact and wrapping of soft tissue structures around bone and cartilage surfaces. The usefulness of the multibody model is demonstrated by modeling the patellofemoral joint of six cadaver knees, using cadaver-specific data for the articular surface and bone geometries, as well as tendon and ligament insertions and muscle lines of actions. Good accuracy was observed when comparing the model patellar kinematic predictions to experimental data (mean ± stand, dev. error in translation: 0.63 ± 1.19 mm, 0.10 ± 0.71 mm, -0.29 ± 0.84 mm along medial, proximal, and anterior directions, respectively; in rotation: -1.41 ± 1.71°, 0.27 ±2.38°, -1.13 ± 1.83° in flexion, tilt and rotation, respectively). The accuracy which can be achieved with this type of model, and the computational efficiency of the algorithm employed in this study may serve in many applications such as computer-aided surgical planning, and real-time computer-assisted surgery in the operating room.     

A Mathematical Formulation for 3D Quasi-Static Multibody Models of Diarthrodial Joints

This study describes a general set of equations for quasi-static analysis of three-dimensional multibody systems, with a particular emphasis on modeling of diarthrodial joints. The model includes articular contact, muscle forces, tendons and tendon pulleys, ligaments, and the wrapping of soft tissue structures around bone and cartilage surfaces. The general set of equations governing this problem are derived using a consistent notation for all types of links, which can be converted conveniently into efficient computer codes. The computational efficiency of the model is enhanced by the use of analytical Jacobians, particularly in the analysis of articular surface contact and wrapping of soft tissue structures around bone and cartilage surfaces. The usefulness of the multibody model is demonstrated by modeling the patellofemoral joint of six cadaver knees, using cadaver-specific data for the articular surface and bone geometries, as well as tendon and ligament insertions and muscle lines of actions. Good accuracy was observed when comparing the model patellar kinematic predictions to experimental data (mean +/- stand. dev. error in translation: 0.63 +/- 1.19 mm, 0.10 +/- 0.71 mm, -0.29 +/- 0.84 mm along medial, proximal, and anterior directions, respectively; in rotation: -1.41 +/- 1.71 degrees, 0.27 +/- 2.38 degrees, -1.13 +/- 1.83 degrees in flexion, tilt and rotation, respectively). The accuracy which can be achieved with this type of model, and the computational efficiency of the algorithm employed in this study may serve in many applications such as computer-aided surgical planning, and real-time computer-assisted surgery in the operating room.     

MRI-based modeling for radiocarpal joint mechanics: validation criteria and results for four specimen-specific models

The objective of this study was to validate the MRI-based joint contact modeling methodology in the radiocarpal joints by comparison of model results with invasive specimen-specific radiocarpal contact measurements from four cadaver experiments. We used a single validation criterion for multiple outcome measures to characterize the utility and overall validity of the modeling approach. For each experiment, a Pressurex film and a Tekscan sensor were sequentially placed into the radiocarpal joints during simulated grasp. Computer models were constructed based on MRI visualization of the cadaver specimens without load. Images were also acquired during the loaded configuration used with the direct experimental measurements. Geometric surface models of the radius, scaphoid and lunate (including cartilage) were constructed from the images acquired without the load. The carpal bone motions from the unloaded state to the loaded state were determined using a series of 3D image registrations. Cartilage thickness was assumed uniform at 1.0 mm with an effective compressive modulus of 4 MPa. Validation was based on experimental versus model contact area, contact force, average contact pressure and peak contact pressure for the radioscaphoid and radiolunate articulations. Contact area was also measured directly from images acquired under load and compared to the experimental and model data. Qualitatively, there was good correspondence between the MRI-based model data and experimental data, with consistent relative size, shape and location of radioscaphoid and radiolunate contact regions. Quantitative data from the model generally compared well with the experimental data for all specimens. Contact area from the MRI-based model was very similar to the contact area measured directly from the images. For all outcome measures except average and peak pressures, at least two specimen models met the validation criteria with respect to experimental measurements for both articulations. Only the model for one specimen met the validation criteria for average and peak pressure of both articulations; however the experimental measures for peak pressure also exhibited high variability. MRI-based modeling can reliably be used for evaluating the contact area and contact force with similar confidence as in currently available experimental techniques. Average contact pressure, and peak contact pressure were more variable from all measurement techniques, and these measures from MRI-based modeling should be used with some caution.     

CoBaltDB: Complete bacterial and archaeal orfeomes subcellular localization database and associated resources

Background  

The functions of proteins are strongly related to their localization in cell compartments (for example the cytoplasm or membranes) but the experimental determination of the sub-cellular localization of proteomes is laborious and expensive. A fast and low-cost alternative approach is in silico prediction, based on features of the protein primary sequences. However, biologists are confronted with a very large number of computational tools that use different methods that address various localization features with diverse specificities and sensitivities. As a result, exploiting these computer resources to predict protein localization accurately involves querying all tools and comparing every prediction output; this is a painstaking task. Therefore, we developed a comprehensive database, called CoBaltDB, that gathers all prediction outputs concerning complete prokaryotic proteomes.     

Specimen-specific predictions of contact stress under physiological loading in the human hip: validation and sensitivity studies

Hip osteoarthritis may be initiated and advanced by abnormal cartilage contact mechanics, and finite element (FE) modeling provides an approach with the potential to allow the study of this process. Previous FE models of the human hip have been limited by single specimen validation and the use of quasi-linear or linear elastic constitutive models of articular cartilage. The effects of the latter assumptions on model predictions are unknown, partially because data for the instantaneous behavior of healthy human hip cartilage are unavailable. The aims of this study were to develop and validate a series of specimen-specific FE models, to characterize the regional instantaneous response of healthy human hip cartilage in compression, and to assess the effects of material nonlinearity, inhomogeneity and specimen-specific material coefficients on FE predictions of cartilage contact stress and contact area. Five cadaveric specimens underwent experimental loading, cartilage material characterization and specimen-specific FE modeling. Cartilage in the FE models was represented by average neo-Hookean, average Veronda Westmann and specimen- and region-specific Veronda Westmann hyperelastic constitutive models. Experimental measurements and FE predictions compared well for all three cartilage representations, which was reflected in average RMS errors in contact stress of less than 25 %. The instantaneous material behavior of healthy human hip cartilage varied spatially, with stiffer acetabular cartilage than femoral cartilage and stiffer cartilage in lateral regions than in medial regions. The Veronda Westmann constitutive model with average material coefficients accurately predicted peak contact stress, average contact stress, contact area and contact patterns. The use of subject- and region-specific material coefficients did not increase the accuracy of FE model predictions. The neo-Hookean constitutive model underpredicted peak contact stress in areas of high stress. The results of this study support the use of average cartilage material coefficients in predictions of cartilage contact stress and contact area in the normal hip. The regional characterization of cartilage material behavior provides the necessary inputs for future computational studies, to investigate other mechanical parameters that may be correlated with OA and cartilage damage in the human hip. In the future, the results of this study can be applied to subject-specific models to better understand how abnormal hip contact stress and contact area contribute to OA.     

Study on effect of graded facetectomy on change in lumbar motion segment torsional flexibility using three-dimensional continuum contact representation for facet joints

Facet joints provide rigidity to the lumbar motion segment and thus protect the disk, particularly against torsional injury. A surgical procedure that fully or partially removes the facet joints (facetectomy) will decrease the mechanical stiffness of the motion segment, and potentially place the disk at risk of injury. Analytical models can be used to understand the effect of facet joints on motion segment stability. Using a facet joint model that represents the contact area as contact between two surfaces rather than as point contact, it was concluded that a substantial sudden change in rotational motion, due to applied torsion moment, was observed after 75 percent of any one of the facet joints was removed. Applied torsional moment loading produced coupled extension motion in the intact motion segment. This coupled motion also experienced a large change following complete unilateral facetectomy. Clinically, the present study showed that surgical intervention in the form of unilateral or bilateral total facetectomy might require fusion to reduce the primary torsion motion.     

Multiscale computational models can guide experimentation and targeted measurements for crop improvement

Computational models of plants have identified gaps in our understanding of biological systems, and have revealed ways to optimize cellular processes or organ‐level architecture to increase productivity. Thus, computational models are learning tools that help direct experimentation and measurements. Models are simplifications of complex systems, and often simulate specific processes at single scales (e.g. temporal, spatial, organizational, etc.). Consequently, single‐scale models are unable to capture the critical cross‐scale interactions that result in emergent properties of the system. In this perspective article, we contend that to accurately predict how a plant will respond in an untested environment, it is necessary to integrate mathematical models across biological scales. Computationally mimicking the flow of biological information from the genome to the phenome is an important step in discovering new experimental strategies to improve crops. A key challenge is to connect models across biological, temporal and computational (e.g. CPU versus GPU) scales, and then to visualize and interpret integrated model outputs. We address this challenge by describing the efforts of the international Crops in silico consortium.     

Congruency Effects on Load Bearing in Diarthrodial Joints

Modelling load bearing in diarthrodial joints is challenging, due to the complexity of the materials, the boundary and interface conditions and the geometry. The articulating surfaces are covered with cartilage layers that are filled with a fluid that plays a major role in load bearing [Mow, V.C., Holmes, M.H., Lai, W.M. (1984) “Survey article: fluid transport and mechanical properties of articular cartilage: a review”, Journal of Biomechanics 17(5), 377–394]. Researchers have tended to approximate joint geometry using axisymmetry [Donzelli, P.S., Spilker, R.L., Ateshian, G.A., Mow, V.C. (1999) “Contact analysis of biphasic transversely isotropic cartilage layers and correlations with tissue failure”, Journal of Biomechanics 32, 1037–1047], often with a rounded upper articulating surface, creating a form of Hertz problem [Donzelli, P.S., Spilker, R.L., Ateshian, G.A., Mow, V.C. (1999) “Contact analysis of biphasic transversely isotropic cartilage layers and correlations with tissue failure”, Journal of Biomechanics 32, 1037–1047]. However, diarthrodial joints (shoulder, hip and knee) are equipped with peripheral structures (glenoid labrum, acetabular labrum and meniscus, respectively) that tend to deepen the joint contact and thus cause initial contact to be established at the periphery of the joint rather than “centrally”. The surface geometries are purposefully incongruent, and the incongruency has a significant effect on the stresses, pressures and pressure gradients inside the tissue. The models show the importance of the peripheral structures and the incongruency from a load-bearing perspective. Joint shapes must provide a compromise between demands for load-bearing, lubrication and the supply of nutrients to the chondrocytes of the cartilage and cells of the peripheral structures. Retention and repair of the functionality of these peripheral structures should be a prime consideration in any surgical treatment of an injured joint.     

An augmented Lagrangian finite element formulation for 3D contact of biphasic tissues

Biphasic contact analysis is essential to obtain a complete understanding of soft tissue biomechanics, and the importance of physiological structure on the joint biomechanics has long been recognised; however, up to date, there are no successful developments of biphasic finite element contact analysis for three-dimensional (3D) geometries of physiological joints. The aim of this study was to develop a finite element formulation for biphasic contact of 3D physiological joints. The augmented Lagrangian method was used to enforce the continuity of contact traction and fluid pressure across the contact interface. The biphasic contact method was implemented in the commercial software COMSOL Multiphysics 4.2^® (COMSOL, Inc., Burlington, MA). The accuracy of the implementation was verified using 3D biphasic contact problems, including indentation with a flat-ended indenter and contact of glenohumeral cartilage layers. The ability of the method to model multibody biphasic contact of physiological joints was proved by a 3D knee model. The 3D biphasic finite element contact method developed in this study can be used to study the biphasic behaviours of the physiological joints.     

Determination of oral mucosal Poisson’s ratio and coefficient of friction from in-vivo contact pressure measurements

Despite their considerable importance to biomechanics, there are no existing methods available to directly measure apparent Poisson’s ratio and friction coefficient of oral mucosa. This study aimed to develop an inverse procedure to determine these two biomechanical parameters by utilizing in vivo experiment of contact pressure between partial denture and beneath mucosa through nonlinear finite element (FE) analysis and surrogate response surface (RS) modelling technique. First, the in vivo denture–mucosa contact pressure was measured by a tactile electronic sensing sheet. Second, a 3D FE model was constructed based on the patient CT images. Third, a range of apparent Poisson’s ratios and the coefficients of friction from literature was considered as the design variables in a series of FE runs for constructing a RS surrogate model. Finally, the discrepancy between computed in silico and measured in vivo results was minimized to identify the best matching Poisson’s ratio and coefficient of friction. The established non-invasive methodology was demonstrated effective to identify such biomechanical parameters of oral mucosa and can be potentially used for determining the biomaterial properties of other soft biological tissues.     

Effects of inserting a pressensor film into articular joints on the actual contact mechanics.

Fuji film has been widely used in studies aimed at obtaining the contact mechanics of articular joints. Once sealed for practical use in biological joints, Fuji Pressensor film has a total effective thickness of 0.30 mm, which is comparable to the cartilage thickness in the joints of many small animals. The average effective elastic modulus of Fuji film is approximately 100 MPa in compression, which is larger by a factor of 100-300 compared to that of normal articular cartilage. Therefore, inserting a Pressensor film into an articular joint will change the contact mechanics of the joint. The measurement precision of the Pressensor film has been determined systematically; however, the changes in contact mechanics associated with inserting the film into joints have not been investigated. This study was aimed at quantifying the changes in the contact mechanics associated with inserting sealed Fuji Pressensor film into joints. Spherical and cylindrical articular joint contact mechanics with and without Pressensor film and for varying degrees of surface congruency were analyzed and compared by using finite element models. The Pressensor film was taken as linearly elastic and the cartilage was assumed to be biphasic, composed of a linear elastic solid phase and an inviscid fluid phase. The present analyses showed that measurements of the joint contact pressures with Fuji Pressensor film will change the maximum true contact pressures by 10-26 percent depending on the loading, geometry of the joints, and the mechanical properties of cartilage. Considering this effect plus the measurement precision of the film (approximately 10 percent), the measured joint contact pressures in a joint may contain errors as large as 14-28 percent.     

An evaluation of three-dimensional diarthrodial joint contact using penetration data and the finite element method

We have developed an approximate method for simulating the three-dimensional contact of soft biphasic tissues in diarthrodial joints under physiological loading. Input to the method includes: (i) kinematic information describing an in vitro joint articulation, measured while the cartilage is deformed under physiological loads, (ii) geometric properties for the relaxed (undeformed) cartilage layers, obtained for the analyses in this study via stereophotogrammetry, and (iii) material parameters for the biphasic constitutive relations used to represent cartilage. Solid models of the relaxed tissue layers are assembled in physiological positions, resulting in a mathematical overlap of the cartilage layers. The overlap distribution is quantified and converted via the biphasic governing equations into applied traction boundary conditions for both the solid and fluid phases for each of the contacting layers. Linear, biphasic, three-dimensional, finite element analysis is performed using the contact boundary conditions derived for each of the contacting layers. The method is found to produce results consistent with the continuity requirements of biphasic contact. Comparison with results from independent, biphasic contact analyses of axisymmetric problems shows that the method slightly underestimates the contact area, leading to an overestimation of the total traction, but yields a good approximation to elastic stress and solid phase displacement.     

Physical validation of a patient-specific contact finite element model of the ankle

A validation study was conducted to determine the extent to which computational ankle contact finite element (FE) results agreed with experimentally measured tibio-talar contact stress. Two cadaver ankles were loaded in separate test sessions, during which ankle contact stresses were measured with a high-resolution (Tekscan) pressure sensor. Corresponding contact FE analyses were subsequently performed for comparison. The agreement was good between FE-computed and experimentally measured mean (3.2% discrepancy for one ankle, 19.3% for the other) and maximum (1.5% and 6.2%) contact stress, as well as for contact area (1.7% and 14.9%). There was also excellent agreement between histograms of fractional areas of cartilage experiencing specific ranges of contact stress. Finally, point-by-point comparisons between the computed and measured contact stress distributions over the articular surface showed substantial agreement, with correlation coefficients of 90% for one ankle and 86% for the other. In the past, general qualitative, but little direct quantitative agreement has been demonstrated with articular joint contact FE models. The methods used for this validation enable formal comparison of computational and experimental results, and open the way for objective statistical measures of regional correlation between FE-computed contact stress distributions from comparison articular joint surfaces (e.g., those from an intact versus those with residual intra-articular fracture incongruity).     

Flux analysis and metabolomics for systematic metabolic engineering of microorganisms

Rational engineering of metabolism is important for bio-production using microorganisms. Metabolic design based on in silico simulations and experimental validation of the metabolic state in the engineered strain helps in accomplishing systematic metabolic engineering. Flux balance analysis (FBA) is a method for the prediction of metabolic phenotype, and many applications have been developed using FBA to design metabolic networks. Elementary mode analysis (EMA) and ensemble modeling techniques are also useful tools for in silico strain design. The metabolome and flux distribution of the metabolic pathways enable us to evaluate the metabolic state and provide useful clues to improve target productivity. Here, we reviewed several computational applications for metabolic engineering by using genome-scale metabolic models of microorganisms. We also discussed the recent progress made in the field of metabolomics and ¹³C-metabolic flux analysis techniques, and reviewed these applications pertaining to bio-production development. Because these in silico or experimental approaches have their respective advantages and disadvantages, the combined usage of these methods is complementary and effective for metabolic engineering.