Dynamic tensile properties of human placenta

Automobile crashes are the largest cause of injury death for pregnant females and the leading cause of traumatic fetal injury mortality in the United States. Computational models, useful tools to evaluate the risk of fetal loss in motor vehicle crashes, are based on a limited number of quasi-static material tests of the placenta. This study presents a total of 20 dynamic uniaxial tensile tests on the maternal side of the placenta and 10 dynamic uniaxial tensile tests on the chorion layer of the placenta. These tests were completed from 6 human placentas to determine material properties at a strain rate of 7.0 strains/s. The results show that the average peak strain at failure for both the maternal portion and the chorion layer of the placenta are similar with a value of 0.56 and 0.61, respectively. However, the average failure stress for the chorion layer, 167.8 kPa, is much higher than the average failure stress for the placenta with the chorionic plate removed, 18.6 kPa. This is due to differences in the structure and function of these layers in the placenta. In summary, dynamic loading data for the placenta have been determined for use in computational modeling of pregnant occupant kinematics in motor vehicle crashes. Moreover the computational model should utilize the material properties for the placenta without the chorion layer.     

Quantifying dynamic mechanical properties of human placenta tissue using optimization techniques with specimen-specific finite-element models

Motor-vehicle crashes are the leading cause of fetal deaths resulting from maternal trauma in the United States, and placental abruption is the most common cause of these deaths. To minimize this injury, new assessment tools, such as crash-test dummies and computational models of pregnant women, are needed to evaluate vehicle restraint systems with respect to reducing the risk of placental abruption. Developing these models requires accurate material properties for tissues in the pregnant abdomen under dynamic loading conditions that can occur in crashes. A method has been developed for determining dynamic material properties of human soft tissues that combines results from uniaxial tensile tests, specimen-specific finite-element models based on laser scans that accurately capture non-uniform tissue-specimen geometry, and optimization techniques. The current study applies this method to characterizing material properties of placental tissue. For 21 placenta specimens tested at a strain rate of 12/s, the mean failure strain is 0.472±0.097 and the mean failure stress is 34.80±12.62 kPa. A first-order Ogden material model with ground-state shear modulus (μ) of 23.97±5.52 kPa and exponent (α₁) of 3.66±1.90 best fits the test results. The new method provides a nearly 40% error reduction (p<0.001) compared to traditional curve-fitting methods by considering detailed specimen geometry, loading conditions, and dynamic effects from high-speed loading. The proposed method can be applied to determine mechanical properties of other soft biological tissues.     

Constitutive behavior of ocular tissues over a range of strain rates

The constitutive behavior of bovine scleral and corneal tissues is measured in tension and compression, at quasi-static and moderate strain rates. Experiments are conducted at strain rates up to about 50 strain per second by a pneumatic testing system developed to overcome noise and measurement difficulties associated with the time dependent test of low impedance materials. Results for the tissues at room and the natural bovine body temperatures are similar and indicate that ocular tissue exhibits nonlinear stiffening for increasing strain rates, a phenomena termed rate hardening. For example, at a tensile strain rate of 29/s, corneal tissue is found to develop 10 times the stress that it does quasi-statically at the same strain. Thus, conventional constitutive models will grossly underpredict stresses occurring in the corneo-scleral shell due to moderate dynamic events. This has implication to the accuracy of ocular injury models, the study of the stress field in the corneo-scleral shell for glaucoma research and tonometry measurements. The measured data at various strain rates is represented using the general framework of a constitutive model that has been used to represent biological tissue mechanical data. Here it is extended to represent the measured data of the ocular tissues over the range of tested strain rates. Its form allows for straightforward incorporation in various numerical codes. The experimental and analytical methods developed here are felt to be applicable to the test of human ocular tissue.     

Methodology to determine failure characteristics of planar soft tissues using a dynamic tensile test

Predicting the injury risk in automotive collisions requires accurate knowledge of human tissues, more particularly their mechanical properties under dynamic loadings. The present methodology aims to determine the failure characteristics of planar soft tissues such as skin, hollow organs and large vessel walls. This consists of a dynamic tensile test, which implies high-testing velocities close to those in automotive collisions. To proceed, I-shaped tissue samples are subjected to dynamic tensile tests using a customized tensile device based on the drop test principle. Data acquisition has especially been adapted to heterogeneous and soft biological tissues given that standard measurement systems (considered to be global) have been completed with a non-contact and full-field strain measurement (considered to be local). This local measurement technique, called the Image Correlation Method (ICM) provides an accurate strain analysis by revealing strain concentrations and avoids damaging the tissue. The methodology has first been applied to human forehead skin and can be further expanded to other planar soft tissues. The failure characteristics for the skin in terms of ultimate stress are 3 MPa +/- 1.5 MPa. The ultimate global longitudinal strains are equal to 9.5%+/-1.9% (Green-Lagrange strain), which contrasts with the ultimate local longitudinal strain values of 24.0%+/-5.3% (Green-Lagrange strain). This difference is a consequence of the tissue heterogeneity, clearly illustrated by the heterogeneous distribution of the local strain field. All data will assist in developing the tissue constitutive law that will be implemented in finite element models.     

Contributions from self-renewal and trafficking to the uterine NK cell population of early pregnancy.

Uterine NK (uNK) cells are abundant in human and murine uteri during decidualization. It is unclear whether precursors of uNK (pre-uNK) cells self-renew or are recruited from other sites. To assess self-renewal of pre-uNK cells, uterine segments from NK cell-competent mice were grafted orthotopically into NK/uNK cell-deficient or wild-type mice. Only in wild-type recipients did decidualized grafts contain uNK cells, indicating that pre-uNK cells do not self-renew in uterus. To identify pre-uNK cell sources, thymus, bone marrow, lymph node, or spleen cells were grafted from virgin or pregnant NK cell-competent donors into mated NK/uNK cell-deficient recipients. Cells from secondary lymphoid tissues of pregnant donors gave high level uNK cell reconstitution, which was independent of chemokine receptors CCR2 or CCR5. Pregnancy-induced changes to lymphocyte-endothelial cell interactions were documented using adhesion of human lymphocytes to frozen mouse tissue sections under shear. A dynamic increase was observed in L-selectin- and alpha(4) integrin-dependent adhesion of CD56(bright) NK cells to decidualizing uterus and in human PBL adhesion to lymph node endothelium. These data support a model that attributes the dramatic increases in human and murine uNK cells during decidualization to precursor cell recruitment.     

Dynamic material properties of the human sclera

As a result of trauma, approximately 30,000 people become blind in one eye every year in the United States. A common injury prediction tool is computational modeling, which requires accurate material properties to produce reliable results. Therefore, the purpose of this study was to determine the dynamic material properties of the human sclera. A high-rate pressurization system was used to create dynamic pressure to the point of rupture in 12 human eyes. Measurements were obtained for the internal pressure, the diameter of the globe, the thickness of the sclera, and the changing coordinates of the optical markers using high-rate video. A relationship between true stress and true strain was determined for the sclera tissue in two directions. It was found that the average maximum true stress was 13.89±4.81 MPa for both the equatorial and meridional directions, the average maximum true strain along the equator was 0.041±0.014, and the average maximum true strain along the meridian was 0.058±0.018. Results show a significant difference in the maximum strain in the equatorial and meridional directions (p=0.02). In comparing these data with previous studies, it is concluded that the human sclera is both anisotropic and viscoelastic. The dynamic material properties presented in this study can be used for advanced models of the human eye to help prevent eye injuries in the future.     

True stress and Poisson's ratio of tendons during loading

Excessive axial tension is very likely involved in the aetiology of tendon lesions, and the most appropriate indicator of tendon stress state is the true stress, the ratio of instantaneous load to instantaneous cross-sectional area (CSA). Difficulties to measure tendon CSA during tension often led to approximate true stress by assuming that CSA is constant during loading (i.e. by the engineering stress) or that tendon is incompressible, implying a Poisson's ratio of 0.5, although these hypotheses have never been tested. The objective of this study was to measure tendon CSA variation during quasi-static tensile loading, in order to assess the true stress to which the tendon is subjected and its Poisson's ratio. Eight equine superficial digital flexor tendons (SDFT, about 30cm long) were tested in tension until failure while the CSA of each tendon was measured in its metacarpal part by means of a linear laser scanner. Axial elongation and load were synchronously recorded during the test. CSA was found to linearly decrease with strain, with a mean decrease at failure of -10.7±2.8% (mean±standard deviation). True stress at failure was 7.1-13.6% higher than engineering stress, while stress estimation under the hypothesis of incompressibility differed from true stress of -6.6 to 2.3%. Average Poisson's ratio was 0.55±0.12 and did not significantly vary with load. From these results on equine SDFT it was demonstrated that tendon in axial quasi-static tension can be considered, at first approximation, as an incompressible material.     

Biomechanical response of human spleen in tensile loading

Blunt splenic injuries are most frequently caused as a result of motor vehicle collisions and are associated with high mortality rates. In order to accurately assess the risk of automotive related spleen injuries using tools such as finite element models, tissue level tolerance values and suitable material models must be developed and validated based on appropriate biomechanical data. This study presents a total of 41 tension tests performed on spleen parenchyma coupons and 29 tension tests performed on spleen capsule/parenchyma coupons. Standard dog-bone coupons were obtained from fresh human spleen and tested within 48 h of death. Each coupon was tested once to failure at one of the four loading rates to investigate the effects of rate dependence. Load and acceleration data were obtained at each of the specimen grips. High-speed video and optical markers placed on the specimens were used to measure local displacement. Failure stress and strain were calculated at the location of failure in the gage length of the coupon. The results of the study showed that both the spleen parenchyma and the capsule are rate dependent, with higher loading rates yielding higher failure stresses and lower failure strains. The results also show that the failure stress of the splenic capsule is significantly greater than that of the underlying parenchyma. Overall, this study provides novel biomechanical data that demonstrate the rate dependent tissue level tolerance values of human spleen tissue in tensile loading, which can aid in the improvement of finite element models used to assess injury risk in blunt trauma.     

Fracture prediction for the proximal femur using finite element models: Part I--Linear analysis.

Over 90 percent of the more than 250,000 hip fractures that occur annually in the United States are the result of falls from standing height. Despite this, the stresses associated with femoral fracture from a fall have not been investigated previously. Our objectives were to use three-dimensional finite element models of the proximal femur (with geometries and material properties based directly on quantitative computed tomography) to compare predicted stress distributions for one-legged stance and for a fall to the lateral greater trochanter. We also wished to test the correspondence between model predictions and in vitro strain gage data and failure loads for cadaveric femora subjected to these loading conditions. An additional goal was to use the model predictions to compare the sensitivity of several imaging sites in the proximal femur which are used for the in vivo prediction of hip fracture risk. In this first of two parts, linear finite element models of two unpaired human cadaveric femora were generated. In Part II, the models were extended to include nonlinear material properties for the cortical and trabecular bone. While there was poor correspondence between strain gage data and model predictions, there was excellent agreement between the in vitro failure data and the linear model, especially using a von Mises effective strain failure criterion. Both the onset of structural yielding (within 22 and 4 percent) and the load at fracture (within 8 and 5 percent) were predicted accurately for the two femora tested. For the simulation of one-legged stance, the peak stresses occurred in the primary compressive trabeculae of the subcapital region.(ABSTRACT TRUNCATED AT 250 WORDS)     

A novel approach to in vivo mitral valve stress analysis

Three-dimensional (3-D) echocardiography allows the generation of anatomically correct and time-resolved geometric mitral valve (MV) models. However, as imaged in vivo, the MV assumes its systolic geometric configuration only when loaded. Customarily, finite element analysis (FEA) is used to predict material stress and strain fields rendered by applying a load on an initially unloaded model. Therefore, this study endeavors to provide a framework for the application of in vivo MV geometry and FEA to MV physiology, pathophysiology, and surgical repair. We hypothesize that in vivo MV geometry can be reasonably used as a surrogate for the unloaded valve in computational (FEA) simulations, yielding reasonable and meaningful stress and strain magnitudes and distributions. Three experiments were undertaken to demonstrate that the MV leaflets are relatively nondeformed during systolic loading: 1) leaflet strain in vivo was measured using sonomicrometry in an ovine model, 2) hybrid models of normal human MVs as constructed using transesophageal real-time 3-D echocardiography (rt-3DE) were repeatedly loaded using FEA, and 3) serial rt-3DE images of normal human MVs were used to construct models at end diastole and end isovolumic contraction to detect any deformation during isovolumic contraction. The average linear strain associated with isovolumic contraction was 0.02 ± 0.01, measured in vivo with sonomicrometry. Repeated loading of the hybrid normal human MV demonstrated little change in stress or geometry: peak von Mises stress changed by <4% at all locations on the anterior and posterior leaflets. Finally, the in vivo human MV deformed minimally during isovolumic contraction, as measured by the mean absolute difference calculated over the surfaces of both leaflets between serial MV models: 0.53 ± 0.19 mm. FEA modeling of MV models derived from in vivo high-resolution truly 3-D imaging is reasonable and useful for stress prediction in MV pathologies and repairs.     

Effect of frozen storage on dynamic tensile properties of human placenta

Dynamic mechanical properties of placenta tissue are needed to develop computational models of pregnant occupants for use in designing restraint systems that protect the fetus and mother. Tests were performed on 21 samples obtained from five human placentas at a rate of 1200 %/s using a set of custom designed thermoelectrically cooled clamps. Approximately half of the samples from all five subjects were tested within 48 h of delivery. The remaining samples were frozen for 5-7 days and then thawed before testing. True failure stresses and strains were not significantly different between fresh and frozen samples (p-value?=?0.858 and 0.551, respectively), suggesting that soft tissue may be stored frozen up to a week without adversely affecting dynamic material response.     

Load transmission in the nasofrontal suture of the pig, Sus scrofa

The nasofrontal suture links the nasal complex with the braincase and is subject to compressive strain during mastication and (theoretically) tensile strain during growth of nasal soft tissues. The suture's ability to transmit compressive and tensile loads therefore affects both cranioskeletal stress distribution and growth. This study investigated the in vitro viscoelastic and failure properties of the nasofrontal suture in the pig, Sus scrofa. Suture specimens from two ages were tested in compression and tension and at fast and slow rates. In additional specimens, strain gauges were applied to the suture and nasal bone for strain measurement during testing. Relaxation testing demonstrated higher elastic moduli in tension than compression, regardless of test rate or pig age. In contrast, maximum elastic moduli from failure tests, as well as peak stresses, were significantly higher in compression than in tension. Sutures from older pigs tended to have higher elastic moduli and peak stresses, significantly so for tensile relaxation moduli. Strain gauge results showed that deformation at the suture was much greater than that of the nasal bone. These data demonstrate the viscoelasticity and deformability of the nasofrontal sutural ligament. The suture achieved maximal resistance to tensile deformation at low loads, corresponding with the low tensile loads likely to occur during growth of nasal soft tissues. In contrast, the maximal stiffness in compression at high loads indicates that the suture functions with a substantial safety factor during mastication.     

Hyperelastic properties of human meniscal attachments

Meniscal attachments are ligamentous tissues anchoring the menisci to the underlying subchondral bone. Currently little is known about the behavior of meniscal attachments, with only a few studies quantitatively documenting their properties. The objective of this study was to quantify and compare the tensile mechanical properties of human meniscal attachments in the transverse direction, curve fit experimental Cauchy stress-stretch data to evaluate the hyperelastic behavior, and couple these results with previously obtained longitudinal data to generate a more complete constitutive model. Meniscal attachment specimens were tested using a uniaxial tension test with the collagen fibers oriented perpendicular to the loading axis. Tests were run until failure and load-optical displacement data was recorded for each test. The medial posterior attachment was shown to have a significantly greater elastic modulus (6.42±0.78 MPa) and ultimate stress (1.73±0.32 MPa) when compared to the other three attachments. The Mooney-Rivlin material model was selected as the best fit for the transverse data and used in conjunction with the longitudinal data. A novel computational approach to determining the transition point between the toe and linear regions is presented for the hyperelastic stress-stretch curves. Results from piece-wise non-linear longitudinal curve fitting correlate well with previous linear elastic and SEM findings. These data can be used to advance the design of meniscal replacements and improve knee joint finite element models.     

A two-step procedure for coupling development and usage of a pair of human neck models

Both finite element models and multi-body models of human head-neck complex had been widely used in neck injuries analysis, as the former could be used to generate detailed stress strain information and the later could generate dynamic responses with high efficiency. Sometimes, detailed stress and strain information were hoped to be obtained more efficiently, but current methods were not effective enough when they were used to analyze responses of human head neck complex to long duration undulate accelerations. In this paper, a two-step procedure for ‘parallel’ development and ‘sequential’ usage of a pair of human head neck models was discussed. The pair of models contained a finite element model and a multi-body model, which were developed based on the coupling ‘parallel’ procedure using the same bio-realistic geometry. After being validated using available data, the pair of human neck models were applied to analyze biomechanical responses of pilot’s neck during arrested landing operation according to the ‘sequential’ procedure, because typical sustained undulate accelerations usually appeared during such processes. The results, including both kinematic and detailed biomechanical responses of human head-neck complex, were obtained with preferable efficiency. This research provided an effective way for biomechanical analysis of human head neck responses to sustained undulate accelerations.     

Expression of RND proteins in human myometrium

RHO GTPases are key regulators of the actin cytoskeleton and stress fiber formation. In the human uterus, activated RHOA forms a complex with RHO-associated protein kinase (ROCK) which inhibits myosin light chain phosphatase (PPP1R12A), causing a calcium-independent increase in myosin light chain phosphorylation and tension (Ca2+ sensitization). Recently discovered small GTP binding RND proteins can inhibit RHOA and ROCK interaction to reduce calcium sensitization. Very little is known about the expression of RND proteins in the human uterus. We tested the hypothesis that the uterine quiescence observed during gestation is mediated by an increase in RND protein expression inhibiting RHOA-ROCK-mediated PPP1R12A phosphorylation. Immunohistochemistry and immunoblotting were used to determine RHOA and RND protein expression and localization in nonpregnant, pregnant nonlaboring, and laboring patients at term and patients in spontaneous preterm labor. Changes in protein expression estimated by densitometry between different patient groups were measured. A significant increase of RND2 and RND3 protein expression was observed in pregnant relative to nonpregnant myometrium associated with a loss of PPP1R12A phosphorylation. RND transfected myometrial cells demonstrated a dramatic loss of stress fiber formation and a "rounding" phenotype. RND upregulation in pregnancy may inhibit RHOA-ROCK-mediated increase in calcium sensitization to facilitate the uterine quiescence observed during gestation.     

Material properties of the placenta under dynamic loading conditions

Trauma during pregnancy especially occurring during car crashes leads to many foetal losses. Numerical modelling is widely used in car occupant safety issue and injury mechanisms analysis and is particularly adapted to the pregnant woman. Material modelling of the gravid uterus tissues is crucial for injury risk evaluation especially for the abruption placentae which is widely assumed as the leading cause of foetal loss. Experimental studies on placenta behaviour in tension are reported in the literature, but none in compression to the authors' knowledge. This lack of data is addressed in this study. To complement the already available experimental literature data on the placenta mechanical behaviour and characterise it in a compression loading condition, 80 indentation tests on fresh placentae are presented. Hyperelastic like mean experimental stress versus strain and corridors are exposed. The results of the experimental placenta indentations compared with the tensile literature results tend to show a quasi-symmetrical behaviour of the tissue. An inverse analysis using simple finite element models has permitted to propose parameters for an Ogden material model for the placenta which exhibits a realistic behaviour in both tension and compression.     

Thromboxane production in the pregnant rat: differential recovery by platelets and uterus following aspirin administration

Radioimmunologic data provide evidence that the pregnant rat uterus produces thromboxane B2 (TXB2). To provide further evidence that this radioimmunologic compound is TXB2, an extract of media incubated with uteri from 21-day pregnant rats was passed through a silicic acid column and each 1-ml eluate was tested for its ability to displace tritiated TXB2 from antibody. One peak was found and it corresponded to that of authentic TXB2 eluted through an identical column. Rechromatographing the peak on a thin-layer plate, the radioimmunologic peak again corresponded with the TXB2 standard. Since blood platelets are a major source of thromboxane, their presence in the vasculature of tissues makes them a possible contaminating factor. Following aspirin (300 mg) intubation into rats on either gestational Day 18, 19 or 20, in vitro production of the TXB2 by isolated uteri and washed platelets was determined and compared to the same tissues from untreated rats. When aspirin was administered 1 day prior to autopsy, TXB2 production by uterine tissue was 32% of the control uterus. Platelet TXB2 production was 25% of control platelets. When aspirin was administered 2 days prior to autopsy, uterine TXB2 production increased to 60% of the control, while platelet TXB2 was 43% of the control. When aspirin was administered 3 days prior to autopsy, uterine TXB2 production was higher than that of control, while platelet TXB2 production was 54% of the control. The more rapid recovery of TXB2 by uterine tissue compared to platelets suggest that the TXB2 produced by uterine tissue is not due solely to platelet contamination.     

Effects of exercise and heat stress on regional blood flow in pregnant sheep

Radioactive microspheres were used to measure cardiac output and blood flow to most major tissues, including those in the pregnant uterus, in late-pregnant ewes at rest and during treadmill exercise (approximately 3-fold increase in metabolic rate for 30 min) in thermoneutral (TN) (dry bulb temperature (Tdb) = 13 degrees C, wet bulb temperature (Twb) = 10 degrees C) and mildly hot (MH) (Tdb = 40 degrees C, Twb = 27 degrees C) environments. Exercise caused major increases in blood flow to respiratory muscles, nonrespiratory limb muscles, and adipose tissue, and flow was decreased to some gastrointestinal tissues, spleen, pancreas, and to placental and nonplacental tissues in the pregnant uterus. Heat exposure had relatively little effect on these exercise-induced changes, except that flow was further increased in the respiratory muscles. Results are compared with those of a similar study on nonpregnant sheep in which changes in muscle, skin, and visceral flows during exercise were attenuated by heat exposure. It is suggested that redistribution of blood flow from the pregnant uterus, which in resting ewes took 22% of cardiac output, is a significant buffer against the potentially deleterious effects of combined exercise and heat stress on blood flow to exercising muscles and thermoregulatory tissues.     

Identifying factors related to Achilles tendon stress, strain, and stiffness before and after 6 months of growth in youth 10-14 years of age

The purposes of this study were (1) determine if youth peak Achilles tendon (AT) strain, peak AT stress, and AT stiffness, measured during an isometric plantar flexion, differed after six months (mos) of growth, and (2) determine if sex, physical activity level (Physical Activity Questionnaire (PAQ-C)), and/or growth rate (GR) were related to these properties. AT stress, strain, and stiffness were quantified in 20 boys (13.47±0.81 years) and 22 girls (11.18±0.82 years) at 2 times (0 and 6 mos). GR (change in height in 6 mos) was not significantly different between boys and girls (3.5±1.4 and 3.4±1.1cm/6 mos respectively). Peak AT strain and stiffness (mean 3.8±0.4% and 128.9±153.6N/mm, respectively) did not differ between testing sessions or sex. Peak AT stress (22.1±2.4 and 24.0±2.1MPa at 0 and 6 mos, respectively) did not differ between sex and increased significantly at 6 mos due to a significant decrease in AT cross-sectional area (40.6±1.3 and 38.1±1.6mm(2) at 0 and 6 mos, respectively) with no significant difference in peak AT force (882.3±93.9 and 900.3± 65.5N at 0 and 6 mos, respectively). Peak AT stress was significantly greater in subjects with greater PAQ-C scores (9.1% increase with 1 unit increase in PAQ-C score) and smaller in subjects with faster GRs (13.8% decrease with 1cm/6 mos increase in GR). These results indicate that of the AT mechanical properties quantified, none differed between sex, and only peak AT stress significantly differed after 6 months and was related to GR and physical activity.