A comprehensive experimental study on material properties of human brain tissue

A comprehensive study on the biomechanical response of human brain tissue is necessary to investigate traumatic brain injury mechanisms. Published brain material property studies have been mostly performed under a specific type of loading, which is insufficient to develop accurate brain tissue constitutive equations. In addition, inconsistent or contradictory data in the literature made it impossible for computational model developers to create a single brain material model that can fit most, if not all, experimental results.     

Mechanical properties of radiation-sterilised human Bone-Tendon-Bone grafts preserved by different methods

Patellar tendon auto- and allo-grafts are commonly used in orthopedic surgery for reconstruction of the anterior cruciate ligaments (ACL). Autografts are mainly used for primary reconstruction, while allografts are useful for revision surgery. To avoid the risk of infectious disease transmission allografts should be radiation-sterilised. As radiation-sterilisation supposedly decreases the mechanical strength of tendon it is important to establish methods of allograft preservation and sterilisation assuring the best quality of grafts and their safety at the same time. Therefore, the purpose of this study was to compare the tensile strength of human patellar tendon (cut out as for ACL reconstruction), preserved by various methods (deep fresh freezing, glycerolisation, lyophilisation) and subsequently radiation-sterilised with doses of 0, 25, 50 or 100 kGy. Bone-Tendon-Bone grafts (BTB) were prepared from cadaveric human patella tendons with both patellar and tibial attachments. BTB grafts were preserved by deep freezing, glycerolisation or lyophilisation and were subsequently radiation-sterilised with doses of 0 (control), 25, 50 or 100 kGy. All samples were subjected to mechanical failure tensile tests with the use of Instron system in order to estimate their mechanical properties. All lyophilised grafts were rehydrated before performing of those tests. Obtained mechanical tests results of examined grafts suggest that deep-frozen irradiated grafts retain their initial mechanical properties to an extent which does not exclude their clinical application. All conducted experiments were approved by the Local Ethical Committee.     

Kinematic motion of the anterior cruciate ligament deficient knee during functionally high and low demanding tasks

The purpose of this study was to determine whether mechanical adaptations were present in patients with anterior cruciate ligament (ACL)-deficient knees during high-demand activities. Twenty-two subjects with unilateral ACL deficiency (11 males and 11 females, 19.6 months after injury) performed five different activities at a comfortable speed (level walking, ascending and descending steps, jogging, jogging to a 90-degree side cutting toward the opposite direction of the tested side). Three-dimensional knee kinematics for the ACL-deficient knees and uninjured contralateral knees were evaluated using the Point Cluster Technique. There was no significant difference in knee flexion angle, but an offset toward the knee in less valgus and more external tibial rotation was observed in the ACL-deficient knee. The tendency was more obvious in high demand motions, and a significant difference was clearly observed in the side cutting motions. These motion patterns, with the knee in less valgus and more external tibial rotation, are proposed to be an adaptive movement to avoid pivot shift dynamically, and reveal evidence in support of a dynamic adaptive motion occurring in ACL-deficient knees.     

Computational stability of human knee joint at early stance in Gait: Effects of muscle coactivity and anterior cruciate ligament deficiency

As one of the most complex and vulnerable structures of body, the human knee joint should maintain dynamic equilibrium and stability in occupational and recreational activities. The evaluation of its stability and factors affecting it is vital in performance evaluation/enhancement, injury prevention and treatment managements. Knee stability often manifests itself by pain, hypermobility and giving-way sensations and is usually assessed by the passive joint laxity tests. Mechanical stability of both the human knee joint and the lower extremity at early stance periods of gait (0% and 5%) were quantified here for the first time using a hybrid musculoskeletal model of the lower extremity. The roles of muscle coactivity, simulated by setting minimum muscle activation at 0–10% levels and ACL deficiency, simulated by reducing ACL resistance by up to 85%, on the stability margin as well as joint biomechanics (contact/muscle/ligament forces) were investigated. Dynamic stability was analyzed using both linear buckling and perturbation approaches at the final deformed configurations in gait. The knee joint was much more stable at 0% stance than at 5% due to smaller ground reaction and contact forces. Muscle coactivity, when at lower intensities (<3% of its maximum active force), increased dynamic stability margin. Greater minimum activation levels, however, acted as an ineffective strategy to enhance stability. Coactivation also substantially increased muscle forces, joint loads and ACL force and hence the risk of further injury and degeneration. A deficiency in ACL decreases total ACL force (by 31% at 85% reduced stiffness) and the stability margin of the knee joint at the heel strike. It also markedly diminishes forces in lateral hamstrings (by up to 39%) and contact forces on the lateral plateau (by up to 17%). Current work emphasizes the need for quantification of the lower extremity stability margin in gait.     

Three-dimensional in vivo kinematics and finite helical axis variables of the ovine stifle joint following partial anterior cruciate ligament transection

Partial anterior cruciate ligament (p-ACL) rupture is a common injury, but the impact of a p-ACL injury on in vivo joint kinematics has yet to be determined in an animal model. The in vivo kinematics of the ovine stifle joint were assessed during ‘normal’ gait, and at 20 and 40 weeks after p-ACL transection (Tx). Gross morphological scoring of the knee was conducted. p-ACL Tx creates significant progressive post-traumatic osteoarthritis (PTOA)-like damage by 40 weeks. Statistically significant increases for flexion angles at hoof-strike (HS) and mid-stance (MST) were seen at 20 weeks post p-ACL Tx and the HS and hoof-off (HO) points at 40 weeks post p-ACL-Tx, therefore increased flexion angles occurred during stance phase. Statistically significant increases in posterior tibial shift at the mid-flexion (MF) and mid-extension (ME) points were seen during the swing phase of the gait cycle at 40 weeks post p-ACL Tx. Correlation analysis showed a strong and significant correlation between kinematic changes (instabilities) and gross morphological score in the inferior-superior direction at 40 weeks post p-ACL Tx at MST, HO, and MF. Further, there was a significant correlation between change in gross morphological combined score (ΔGCS) and the change in location of the helical axis in the anterior direction (ΔsAP) after p-ACL Tx for all points analyzed through the gait cycle. This study quantified in vivo joint kinematics before and after p-ACL Tx knee injury during gait, and demonstrated that a p-ACL knee injury leads to both PTOA-like damage and kinematic changes.     

Determination of the axial and circumferential mechanical properties of the skin tissue using experimental testing and constitutive modeling

The skin, being a multi-layered material, is responsible for protecting the human body from the mechanical, bacterial, and viral insults. The skin tissue may display different mechanical properties according to the anatomical locations of a body. However, these mechanical properties in different anatomical regions and at different loading directions (axial and circumferential) of the mice body to date have not been determined. In this study, the axial and circumferential loads were imposed on the mice skin samples. The elastic modulus and maximum stress of the skin tissues were measured before the failure occurred. The nonlinear mechanical behavior of the skin tissues was also computationally investigated through a suitable constitutive equation. Hyperelastic material model was calibrated using the experimental data. Regardless of the anatomic locations of the mice body, the results revealed significantly different mechanical properties in the axial and circumferential directions and, consequently, the mice skin tissue behaves like a pure anisotropic material. The highest elastic modulus was observed in the back skin under the circumferential direction (6.67 MPa), while the lowest one was seen in the abdomen skin under circumferential loading (0.80 MPa). The Ogden material model was narrowly captured the nonlinear mechanical response of the skin at different loading directions. The results help to understand the isotropic/anisotropic mechanical behavior of the skin tissue at different anatomical locations. They also have implications for a diversity of disciplines, i.e., dermatology, cosmetics industry, clinical decision making, and clinical intervention.     

Mechanical responses of the periodontal ligament based on an exponential hyperelastic model: a combined experimental and finite element method

The V–W exponential hyperelastic model is adopted to describe the instantaneous elastic response of the periodontal ligament (PDL). The general theoretical framework of constitutive modeling is described based on nonlinear continuum mechanics, and the elasticity tensor used to develop UMAT subroutine is formulated. Nanoindentation experiment is performed to characterize mechanical properties of an adult pig PDL specimen. Then the experiment is simulated by using the finite element (FE) analysis. Meanwhile, the optimized material parameters are identified by the inverse FE method. The good agreement between the simulated results and experimental data demonstrates that the V–W model is capable of describing the mechanical behavior of the PDL. Therefore, the model and its implementation into FE code are validated. By using the model, we simulate the tooth movement under orthodontic loading to predict the mechanical responses of the PDL. The results show that local concentrations of stress and strain in the PDL are found.     

In vivo assessment of the interaction of patellar tendon tibial shaft angle and anterior cruciate ligament elongation during flexion

A potential cause of non-contact anterior cruciate ligament (ACL) injury is landing on an extended knee. In line with this hypothesis, studies have shown that the ACL is elongated with decreasing knee flexion angle. Furthermore, at low flexion angles the patellar tendon is oriented to increase the anterior shear component of force acting on the tibia. This indicates that knee extension represents a position in which the ACL is taut, and thus may have an increased propensity for injury, particularly in the presence of excessive force acting via the patellar tendon. However, there is very little in vivo data to describe how patellar tendon orientation and ACL elongation interact during flexion. Therefore, this study measured the patellar tendon tibial shaft angle (indicative of the relative magnitude of the shear component of force acting via the patellar tendon) and ACL length in vivo as subjects performed a quasi-static lunge at varying knee flexion angles. Spearman rho rank correlations within each individual revealed that flexion angles were inversely correlated to both ACL length (rho = −0.94 ± 0.07, mean ± standard deviation, p < 0.05) and patellar tendon tibial shaft angle (rho = −0.99 ± 0.01, p < 0.05). These findings indicate that when the knee is extended, the ACL is both elongated and the patellar tendon tibial shaft angle is increased, resulting in a relative increase in anterior shear force on the tibia acting via the patellar tendon. Therefore, these data support the hypothesis that landing with the knee in extension is a high risk scenario for ACL injury.     

Inflammatory and healing environment in synovial fluid after anterior cruciate ligament reconstruction: Granulocytes and endogenous opioids as new targets of postoperative pain

BackgroundBiological processes after anterior cruciate ligament reconstruction (ACLR) is crucial for recovery. However, alterations in the of synovial fluid cell population during the acute phase following ACLR and the relationship between these cells and postoperative pain is unclear. The goal of this study was to reveal alterations in synovial fluid cell population during the acute phase following ACLR and relationship between postoperative pain and proportion of synovial fluid cells.MethodsSynovial fluids were obtained from all patients (n = 50) before surgery and from patients who showed hydrarthrosis at days 4 (n = 25), and 21 (n = 42) post-surgery. The cell population was analyzed by flow cytometry. IL1β, IL8, and met-enkephalin in synovial fluid were quantitated by enzyme-linked immunosorbent assay. Patients answered numerical rating scale (NRS) questionnaire at 4 days and approximately 4 weeks postoperatively.ResultsThe granulocyte population was significantly higher at 4 days after surgery than at any other time points. The population of macrophages was 3.2 times and 7.7 times as high as at surgery on days 4 and 21, respectively. T cell population was significantly higher 21 days after surgery compared to 4 days after surgery. All NRS 4 weeks after surgery showed a significant negative correlation with the granulocyte population in synovial fluid 4 days after surgery. Granulocyte population in synovial fluid significantly correlated with the levels of IL1β and IL8. Postoperative pain at rest tended to decrease with an increase in met-enkephalin concentration 4 days after ACLR.ConclusionsSynovial fluid after ACLR had an inflammatory environment at early time points and a healing environment in the subsequent phase about concerning to the cellular composition. A proportion of synovial fluid cells and endogenous opioids affected postoperative pain.     

The evolution of tendon--morphology and material properties

Phylogenetically, tendinous tissue first appears in the invertebrate chordate Branchiostoma as myosepta. This two-dimensional array of collagen fibers is highly organized, with fibers running along two primary axes. In hagfish the first linear tendons appear and the myosepta have developed specialized regions with unidirectional fiber orientation-a linear tendon within the flat sheet of myoseptum. Tendons react to compressive load by first forming a fibrocartilaginous pad, and under severe stress, sesamoid bones. Evidence for this ability to react to load first arises in the cartilaginous fish, here documented in a tendon from the jaw of a hard-prey crushing stingray. Sesamoid bones are common in bony fish and also in tetrapods. Tendons will also calcify under tensile loads in some groups of birds, and this reaction to load is seen in no other vertebrates. We conclude that the evolutionary history of tendon gives us insight into the use of model systems for investigating tendon biology. Using mammal and fish models may be more appropriate than avian models because of the apparent evolution of a novel reaction to tensile loads in birds.     

Analytical and multibody modeling for the power analysis of standing jumps

Two methods for the power analysis of standing jumps are proposed and compared in this article. The first method is based on a simple analytical formulation which requires as input the coordinates of the center of gravity in three specified instants of the jump. The second method is based on a multibody model that simulates the jumps processing the data obtained by a three-dimensional (3D) motion capture system and the dynamometric measurements obtained by the force platforms. The multibody model is developed with OpenSim, an open-source software which provides tools for the kinematic and dynamic analyses of 3D human body models. The study is focused on two of the typical tests used to evaluate the muscular activity of lower limbs, which are the counter movement jump and the standing long jump. The comparison between the results obtained by the two methods confirms that the proposed analytical formulation is correct and represents a simple tool suitable for a preliminary analysis of total mechanical work and the mean power exerted in standing jumps.     

Material and functional properties of articular cartilage and patellofemoral contact mechanics in an experimental model of osteoarthritis

The purposes of this study were to determine the in situ functional and material properties of articular cartilage in an experimental model of joint injury, and to quantify the corresponding in situ joint contact mechanics. Experiments were performed in the anterior cruciate ligament (ACL) transected knee of the cat and the corresponding, intact contralateral knee, 16 weeks following intervention. Cartilage thickness, stiffness, effective Young’s modulus, and permeability were measured and derived from six locations of the knee. The total contact area and peak pressures in the patellofemoral joint were obtained in situ using Fuji Pressensor film, and comparisons between experimental and contralateral joint were made for corresponding loading conditions. Total joint contact area and peak pressure were increased and decreased significantly (=0.01), respectively, in the experimental compared to the contralateral joint. Articular cartilage thickness and stiffness were increased and decreased significantly (=0.01), respectively, in the experimental compared to the contralateral joint in the four femoral and patellar test locations. Articular cartilage material properties (effective Young’s modulus and permeability) were the same in the ACL-transected and intact joints. These results demonstrate for the first time the effect of changes in articular cartilage properties on the load transmission across a joint. They further demonstrate a substantial change in the joint contact mechanics within 16 weeks of ACL transection. The results were corroborated by theoretical analysis of the contact mechanics in the intact and ACL-transected knee using biphasic contact analysis and direct input of cartilage properties and joint surface geometry from the experimental animals. We conclude that the joint contact mechanics in the ACL-transected cat change within 16 weeks of experimental intervention.     

Biomechanics of changes in ACL and PCL material properties or prestrains in flexion under muscle force-implications in ligament reconstruction

The effects of changes in cruciate ligament material and prestrain on knee joint biomechanics following ligament reconstruction surgery by a tendon are not adequately known. A 3D nonlinear finite element model of the entire knee joint was used to investigate the joint response at different flexion angles under a quadriceps force while varying ACL and PCL initial strains or material properties. The ACL and PCL forces as well as tibiofemoral contact forces/areas substantially increased with greater ACL or PCL initial strains or stiffness. The patellofemoral contact force slightly increased whereas the tibial extensor moment slightly decreased with tenser or stiffer ACL. Reverse trends were predicted with slacker ACL. Results confirm the hypotheses that changes in the prestrain of one cruciate ligament substantially influence the force in the other cruciate ligament and the entire joint and that the use of the patellar tendon (PT) as a replacement for cruciate ligaments markedly alters the joint biomechanics with trends similar to those predicted when increasing prestrains. Forces in both ACL and PCL ligaments increased as one of them became tenser or stiffer and diminished as it became slacker. These results have important consequences in joint biomechanics following ligament injuries or replacement and tend to recommend the use of grafts with smaller prestrains (i.e. slacker than intact) when using the PT as the replacement material with stiffness greater than that of replaced ligament itself.     

Carbonic anhydrase inhibitory properties of novel benzylsulfamides using molecular modeling and experimental studies

In this study, a series of sulfamoyl carbamates and sulfamide derivatives were synthesized. Six commercially available benzyl amines and BnOH were reacted with chlorosulfonyl isocyanate (CSI) to give sulfamoyl carbamates. Pd–C catalyzed hydrogenolysis reactions of carbamates afforded sulfamides. The inhibition effects of novel benzylsulfamides on the carbonic anhydrase I, and II isoenzymes (CA I, and CA II) purified from fresh human blood red cells were determined by Sepharose-4B-L-Tyrosine-sulfanilamide affinity chromatography. In vitro studies were shown that all of novel synthesized benzylsulfamide analogs inhibited, concentration dependently, both hCA isoenzyme activities. The novel benzylsulfamide compounds investigated here exhibited nanomolar inhibition constants against the two isoenzymes. K_i values were in the range of 28.48 ± 0.01–837.09 ± 0.19 nM and 112.01 ± 0.01–268.01 ± 0.22 nM for hCAI and hCA II isoenzymes, respectively. Molecular modeling approaches were also applied for studied compounds.     

Comparison of viscoelastic, structural, and material properties of double-looped anterior cruciate ligament grafts made from bovine digital extensor and human hamstring tendons

Due to ready availability, decreased cost, and freedom from transmissible diseases in humans such as hepatitis and AIDS, it would be advantageous to use tendon grafts from farm animals as a substitute for human tendon grafts in in vitro experiments aimed at improving the outcome of anterior cruciate ligament (ACL) reconstructive surgery. Thus the objective of this study was to determine whether an anterior cruciate ligament (ACL) graft composed of two loops of bovine common digital extensor tendon has the same viscoelastic, structural, and material properties as a graft composed of a double loop of semitendinosus and gracilis tendons from humans. To satisfy this objective, grafts were constructed from each tissue source. The cross-sectional area was measured using an area micrometer, and each graft was then pulled using a materials testing system while submerged in a saline bath. Using two groups of tendon grafts (n = 10), viscoelastic tests were conducted over a three-day period during which a constant displacement load relaxation test was followed by a constant amplitude, cyclic load creep test (first day), a constant load creep test (second day), and an incremental cyclic load creep test (third day). Load-to-failure tests were performed on two different groups of grafts (n = 8). When the viscoelastic behavior was compared, there were no significant differences in the rate of load decay or the final load (relaxation test) and rates of displacement increase or final displacements (creep tests) (p > 0.115). To compare both the structural and material properties in the toe region (i.e., < 250 N) of the load-elongation curve, the tangent stiffness and modulus functions were computed from parameters used in an exponential model fit to the load (stress)-elongation (strain) data. Although one of the two parameters in the functions was different statistically, this difference translated into a difference of only 0.03 mm in displacement at 250 N of load. In the linear region (i.e., 50-75 percent of ultimate load) of the load-elongation curve, the linear stiffness of the two graft types compared closely (444 N/mm for bovine and 418 N/mm for human) (p = 0.341). At failure, the ultimate loads (2901 N and 2914 N for bovine and human, respectively) and the ultimate stresses (71.8 MPa and 65.6 MPa for bovine and human, respectively) were not significantly different (p > 0.261). The theoretical effect of any differences in properties between these two grafts on the results of two types of in vitro experiments (i.e., effect of surgical variables on knee laxity and structural properties of fixation devices) are discussed. Despite some statistical differences in the properties evaluated, these differences do not translate into important effects on the dependent variables of interest in the experiments. Thus the bovine tendon graft can be substituted for the human tendon graft in both types of experiments.     

Torsion of the human left ventricle: experimental analysis and computational modeling

We set a twofold investigation: we assess left ventricular (LV) rotation and twist in the human heart through 3D-echocardiographic speckle tracking, and use representative experimental data as benchmark with respect to numerical results obtained by solving our mechanical model of the LV. We aim at new insight into the relationships between myocardial contraction patterns and the overall behavior at the scale of the whole organ. It is concluded that torsional rotation is sensitive to transmural gradients of contractility which is assumed linearly related to action potential duration (APD). Pressure-volume loops and other basic strain measures are not affected by these gradients. Therefore, realistic torsional behavior of human LV may indeed correspond to the electrophysiological and functional differences between endocardial and epicardial cells recently observed in non-failing hearts. Future investigations need now to integrate the mechanical model proposed here with minimal models of human ventricular APD to drive excitation-contraction coupling transmurally.     

Sequence analysis and homology modeling of peroxidase from Medicago sativa

Plant peroxidases are one of the most extensively studied group of enzymes which find applications in the environment, health,pharmaceutical, chemical and biotechnological processes. Class III secretary peroxidase from alfalfa (Medicago sativa) has beencharacterized using bioinformatics approach Physiochemical properties and topology of alfalfa peroxidase were compared withthat of soybean and horseradish peroxidase, two most popular commercially available peroxidase preparations. Lower value ofinstability index as predicted by ProtParam and presence of extra disulphide linkages as predicted by Cys_REC suggested alfalfaperoxidase to be more stable than either of the commercial preparations. Multiple Sequence Alignment (MSA) with otherfunctionally similar proteins revealed the presence of highly conserved catalytic residues. Three dimensional model of alfalfaperoxidase was constructed based on the crystal structure of soybean peroxidase (PDB Id: 1FHF A) by homology modellingapproach. The model was checked for stereo chemical quality by PROCHECH, VERIFY 3D, WHAT IF, ERRAT, 3D MATCH ANDProSA servers. The best model was selected, energy minimized and used to analyze structure function relationship with substratehydrogen peroxide by Autodock 4.0. The enzyme substrate complex was viewed with Swiss PDB viewer and one residue ASP43was found to stabilize the interaction by hydrogen bonds. The results of the study may be a guiding point for further investigationson alfalfa peroxidase.     

Structural modeling and electrostatic properties of aspartate transcarbamylase from Saccharomyces cerevisiae

In Saccharomyces cerevisiae the first two reactions of the pyrimidine pathway are catalyzed by a multifunctional protein which possesses carbamylphosphate synthetase and aspartate transcarbamylase activities. Genetic and proteolysis studies suggested that the ATCase activity is carried out by an independently folded domain. In order to provide structural information for ongoing mutagenesis studies, a model of the three-dimensional structure of this domain was generated on the basis of the known X-ray structure of the related catalytic subunit from E. coli ATCase. First, a model of the catalytic monomer was built and refined by energy minimization. In this structure, the conserved residues between the two proteins were found to constitute the hydrophobic core whereas almost all the mutated residues are located at the surface. Then, a trimeric structure was generated in order to build the active site as it lies at the interface between adjacent chains in the E. coli catalytic trimer. After docking a bisubstrate analog into the active site, the whole structure was energy minimized to regularize the interactions at the contact areas between subunits. The resulting model is very similar to that obtained for the E. coli catalytic trimer by X-ray crystallography, with a remarkable conservation of the structure of the active site and its vicinity. Most of the interdomain and intersubunit interactions that are essential for the stability of the E. coli catalytic trimer are maintained in the yeast enzyme even though there is only 42% identity between the two sequences. Free energy calculations indicate that the trimeric assembly is more stable than the monomeric form. Moreover an insertion of four amino acids is localized in a loop which, in E. coli ATCase, is at the surface of the protein. This insertion exposes hydrophobic residues to the solvent. Interestingly, such an insertion is present in all the eukaryotic ATCase genes sequenced so far, suggesting that this region is interacting with another domain of the multifunctional protein. © 1994 Wiley-Liss, Inc.     

Uncertainty analysis of material properties and morphology parameters in numerical models regarding the motion of lumbar vertebral segments

Abstract

The kinematics of a spinal motion segment is determined by the material properties of the soft-tissue and the morphology. The material properties can vary within subjects and between vertebral levels, leading to a wide possible range of motion of a spinal segment independently on its morphology. The goal of this numerical study was to identify the most influential material parameters concerning the kinematics of a spinal motion segment and their plausible ranges. Then, a method was tested to deduce the material properties automatically, based on a given ROM and morphology. A fully parametric finite element model of the morphology and material properties of a lumbar spinal motion segment was developed. The impact of uncertainty of twelve spinal material parameters, as well as the size of the gap between the articular surfaces of the facet joints was examined. The simulation results were compared to our own in vitro data. The flexibility of a lumbar segment was especially influenced by the properties of the anterior annulus region, the facet gap size and the interspinous ligament. The high degree of uncertainty in the material properties and facet gap size published in the literature can lead to a wide scatter in the motion of a spinal segment, with a range of 6°-17° in the intact condition in flexion/extension, from 5°-22° in lateral bending and from 3°-14° in axial rotation. Statistical analysis of the variability might help to estimate the sensitivity and total uncertainty propagated through biomechanical simulations, affecting the reliability of the predictions.