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To evaluate the biocompatibility of silk gel for cervical injection.Silk gel was injected into the cervix of pregnant rats on day 13 (n = 11) and harvested at day 17. Histology of silk gel was compared with suture controls. Also, human cervical fibroblasts were cultured on silk gel and tissue culture plastic (TCP) in vitro. Cell viability, proliferation, metabolic activity, gene expression (COL1A1, COL3A1, and COX2), and release of proinflammatory mediators (interleukin [IL] 6 and IL-8) were evaluated.In vivo, a mild foreign body response was seen surrounding the silk gel and suture controls. In vitro, cervical fibroblasts were viable, metabolically active, and proliferating at 72 hours. Release of IL-6 and IL-8 was similar on silk gel and TCP. Collagen and COX2 gene expression was similar or slightly decreased compared with TCP.Silk gel was well tolerated in vivo and in vitro, which supports continuing efforts to develop silk gels as an alternative to cervical cerclage.

Globally, an estimated 13 million preterm babies are born each year. These babies are at increased risk of infant mortality and life-long health complications. Interventions to prevent preterm birth (PTB) require an understanding of processes driving parturition. Prostaglandins (PGs) have diverse functions in parturition, including regulation of uterine contractility and tissue remodeling. Our studies on cervical remodeling in mice suggest that although local synthesis of PGs are not increased in term ripening, transcripts encoding PG-endoperoxide synthase 2 (Ptgs2) are induced in lipopolysaccharide (LPS)-mediated premature ripening. This study provides evidence for two distinct pathways of cervical ripening: one dependent on PGs derived from paracrine or endocrine sources and the other independent of PG actions. Cervical PG levels are increased in LPS-treated mice, a model of infection-mediated PTB, consistent with increases in PG synthesizing enzymes and reduction in PG-metabolizing enzymes. Administration of SC-236, a PTGS2 inhibitor, along with LPS attenuated cervical softening, consistent with the essential role of PGs in LPS-induced ripening. In contrast, during term and preterm ripening mediated by the antiprogestin, mifepristone, cervical PG levels, and expression of PG synthetic and catabolic enzymes did not change in a manner that supports a role for PGs. These findings in mice, supported by correlative studies in women, suggest PGs do not regulate all aspects of the parturition process. Additionally, it suggests a need to refocus current strategies toward developing therapies for the prevention of PTB that target early, pathway-specific processes rather than focusing on common late end point mediators of PTB.

Traumatic brain injury (TBI) and hemorrhagic shock (HS) are major causes of trauma-related deaths and are especially lethal as a combined insult. Previously, we showed that early administration of fresh frozen plasma (FFP) decreased the size of the brain lesion and associated swelling in a swine model of combined TBI+HS. We have also shown separately that addition of valproic acid (VPA) to the resuscitation protocol attenuates inflammatory markers in the brain as well as the degree of TBI. The current study was performed to determine whether a combined FFP+VPA treatment strategy would exert a synergistic effect.Yorkshire swine (42-50 kg) were instrumented to measure hemodynamic parameters, intracranial pressure, and brain tissue oxygenation. TBI was created through a 20-mm craniotomy using a computer-controlled cortical impactor: 15-mm cylindrical tip impactor at 4 m/s velocity, 100 ms dwell time, and 12-mm penetration depth. The TBI was synchronized with the initiation of volume-controlled hemorrhage (40 ± 5% of total blood volume). After a 2-hour period of shock, animals were randomized to 1 of 3 resuscitation groups (n = 5 per group): (1) 0.9% saline (NS); (2) FFP; and (3) FFP and VPA 300 mg/kg (FFP+VPA). The resuscitative volume for FFP was equivalent to the shed blood, whereas NS was 3 times this volume. VPA treatment was started 1 hour after hemorrhage. Animals were monitored for 6 hours post-resuscitation. At this time the brains were harvested, sectioned into 5-mm slices, and stained with 2,3,5-triphenyltetrazolium chloride to quantify the lesion size (mm(3)) and brain swelling (percent change compared with the uninjured side).The combined TBI+HS model resulted in a highly reproducible brain injury. Lesion size and brain swelling (mean value ± standard error of the mean) in the FFP+VPA group (1,459 ± 218 mm(3) and 13 ± 1%, respectively) were less than the NS group (3,285 ± 131 mm(3) [P.001] and 37 ± 2% [P.001], respectively), and the FFP alone group (2,160 ± 203 mm(3) [P.05] and 22 ± 1% [P.001], respectively).In a large animal model of TBI+HS, early treatment with a combination of FFP and VPA decreases the size of brain lesion and the associated swelling.

Woven fabric is used in a wide variety of military and commercial products—both in neat form and as the reinforcement phase of composites. In many applications, yarn slip, the relative sliding of the yarns composing the weave, is an important mode of deformation or failure. Yarn slip can significantly change the energy absorption capacity and yarn density of the fabric and also cause yarns to unravel from the weave. Virtually all existing models for woven fabric that allow yarn slip are discrete in nature. They simulate every yarn in the weave and are therefore computationally expensive and difficult to integrate with other material models. A promising alternative to discrete models is the mesostructure-based continuum technique. With this technique, homogenized continuum properties are determined from a deforming analytic model of the fabric mesostructure at each material point. Yarn-level mechanisms of deformation are thus captured without the computational cost of simulating every yarn in the fabric. However, existing mesostructure-based continuum models treat the yarns as pinned together at the cross-over points of the weave, and an operative model that allows yarn slip has not been published. Here, we introduce a mesostructure-based continuum model that permits yarn slip and use the model to simulate the ballistic impact of woven fabric. In our approach, the weave is the continuum substrate on which the model is anchored, and slip of the yarns occurs relative to the weave continuum. The cross-over points of the weave act as the material points of the continuum, and the evolution of the local weave mesostructure at each point of the continuum is represented by state variables. At the same time, slip velocity fields simulate the slip of each yarn family relative to the weave continuum and therefore control the evolution of the yarn pitch. We found that simulating yarn slip significantly improves finite element predictions of the ballistic impact of a Kevlar ® woven fabric, in particular by increasing the energy absorbed at high initial projectile velocities. Further simulations elucidate the micromechanisms of deformation of ballistic impact of woven fabric with yarn slip. Our findings suggest ways to improve the performance of flexible armor and indicate that this approach has the potential to simulate many other types of woven fabric in applications in which yarn slip occurs.

Preterm birth affects over 12% of all pregnancies in the United States for an annual healthcare cost of $26 billion. Preterm birth is a multifactorial disorder but cervical abnormalities are a prominent feature in many patients. Women with a short cervix are known to be at increased risk for preterm birth and a short cervix is used to target therapy to prevent preterm birth. Although the clinical significance of a short cervix is well known, the three-dimensional anatomical changes that lead to cervical shortening are poorly understood. Here, we review our previous studies of the three-dimensional anatomy of the cervix and uterus during pregnancy. The rationale for these studies was to improve our understanding of the deformation mechanisms leading to cervical shortening. Both magnetic resonance imaging and three-dimensional (3D) ultrasound were used to obtain anatomical data in healthy, pregnant volunteers. Solid models were constructed from the 3D imaging data. These solid models were used to create numerical models suitable for biomechanical simulation. Three simulations were studied: cervical funneling, uterine growth, and fundal pressure. These simulations showed that cervical changes are a complex function of the tissue properties of the cervical stroma, the loading conditions associated with pregnancy and the 3D anatomical geometry of the cervix and surrounding structures. An improved understanding of these cervical changes could point to new approaches to prevent undesired cervical shortening. This new insight should lead to therapeutic strategies to delay or prevent preterm birth.

Cervical dysfunction contributes to a significant number of preterm births and is a common cause of morbidity and mortality in newborn infants. Cervical dysfunction is related to weakened load bearing properties of the collagen-rich cervical stroma. However, the mechanisms responsible for cervical collagen changes during pregnancy are not well defined. It is known that blood flow and oxygen tension significantly increase in reproductive tissues during pregnancy. To examine the effect of oxygen tension, a key mediator of tissue homeostasis, on the formation of cervical-like tissue in vitro, we grew primary human cervical cells in both two-dimensional (2D) and three-dimensional (3D) culture systems at 5% and 20% oxygen. Immunofluorescence studies revealed a stable fibroblast phenotype across six passages in all subjects studied (n=5). In 2D culture for 2 weeks, 20% oxygen was associated with significantly increased collagen gene expression (p

Cervical shortening and cervical insufficiency contribute to a significant number of preterm births. However, the deformation mechanisms that control how the cervix changes its shape from long and closed to short and dilated are not clear. Investigation of the biomechanical problem is limited by (1) lack of thorough characterization of the three-dimensional anatomical changes associated with cervical deformation and (2) difficulty measuring cervical tissue properties in vivo. The objective of the present study was to explore the feasibility of using three-dimensional ultrasound and fundal pressure to obtain anatomically-accurate numerical models of large-strain cervical deformation during pregnancy and enable noninvasive assessment of cervical-tissue compliance. Healthy subjects ( n = 6) and one subject with acute cervical insufficiency in the midtrimester were studied. Extended field-of-view ultrasound images were obtained of the entire uterus and cervix. These images aided construction of anatomically accurate numerical models. Cervical loading was achieved with fundal pressure, which was quantified with a vaginal pressure catheter. In one subject, the anatomical response to fundal pressure was matched by a model-based simulation of the deformation response, thereby deriving the corresponding cervical mechanical properties and showing the feasibility of noninvasive assessment of compliance. The results of this pilot study demonstrate the feasibility of a biomechanical modeling framework for estimating cervical mechanical properties in vivo. An improved understanding of cervical biomechanical function will clarify the pathophysiology of cervical shortening.

Characterizing the dynamic mechanical properties of brain tissue is deemed important for developing a comprehensive knowledge of the mechanisms underlying brain injury. The results gathered to date on the tissue properties have been mostly obtained in vitro. Learning how these results might differ quantitatively from those encountered in vivo is a critical step towards the development of biofidelic brain models. The present study provides novel and unique experimental results on, and insights into, brain biorheology in vivo, in situ and in vitro, at large deformations, in the quasi-static and dynamic regimes. The nonlinear dynamic response of the cerebral cortex was measured in indentation on the exposed frontal and parietal lobes of anesthetized porcine subjects. Load-unload cycles were applied to the tissue surface at sinusoidal frequencies of 10, 1, 0.1 and 0.01 Hz. Ramp-relaxation tests were also conducted to assess the tissue viscoelastic behavior at longer times. After euthanasia, the indentation test sequences were repeated in situ on the exposed cortex maintained in its native configuration within the cranium. Mixed gray and white matter samples were subsequently excised from the superior cortex to be subjected to identical indentation test segments in vitro within 6-7 h post mortem. The main response features (e.g. nonlinearities, rate dependencies, hysteresis and conditioning) were measured and contrasted in vivo, in situ and in vitro. The indentation response was found to be significantly stiffer in situ than in vivo. The consistent, quantitative set of mechanical measurements thereby collected provides a preliminary experimental database, which may be used to support the development of constitutive models for the study of mechanically mediated pathways leading to traumatic brain injury.

The dynamic behavior of porcine brain tissue, obtained from a series of in vitro observations and experiments, is analyzed and described here with the aid of a large strain, nonlinear, viscoelastic constitutive model. Mixed gray and white matter samples excised from the superior cortex were tested in unconfined uniaxial compression within 15h post mortem. The test sequence consisted of three successive load-unload segments at strain rates of 1, 0.1 and 0.01 s⁻¹, followed by stress relaxation (n=25). The volumetric compliance of the tissue was assessed for a subset of specimens (n=7) using video extensometry techniques. The tissue response exhibited moderate compressibility, substantial nonlinearity, hysteresis, conditioning and rate dependence. A large strain kinematics nonlinear viscoelastic model was developed to account for the essential features of the tissue response over the entire deformation history. The corresponding material parameters were obtained by fitting the model to the measured conditioned response (axial and volumetric) via a numerical optimization scheme. The model successfully captures the observed complexities of the material response in loading, unloading and relaxation over the entire range of strain rates. The accuracy of the model was further verified by comparing model predictions with the tissue response in unconfined compression at higher strain rate (10 s⁻¹) and with literature data in uniaxial tension. The proposed constitutive framework was also found to be adequate to model the loading response of brain tissue in uniaxial compression over a wider range of strain rates (0.01-3000 s⁻¹), thereby providing a valuable tool for simulations of dynamic transients (impact, blast/shock wave propagation) leading to traumatic brain injury.

Woven fabric is an increasingly important component of many defense and commercial systems, including deployable structures, restraint systems, numerous forms of protective armor, and a variety of structural applications where it serves as the reinforcement phase of composite materials. With the prevalence of these systems and the desire to explore new applications, a comprehensive, computationally efficient model for the deformation of woven fabrics is needed. However, modeling woven fabrics is difficult due, in particular, to the need to simulate the response both at the scale of the entire fabric and at the meso-level, the scale of the yarns that compose the weave. Here, we present finite elements for the simulation of the three-dimensional, high-rate deformation of woven fabric. We employ a continuum-level modeling technique that, through the use of an appropriate unit cell, captures the evolution of the mesostructure of the fabric without explicitly modeling every yarn. Displacement degrees of freedom and degrees of freedom representing the change in crimp amplitude of each yarn family fully determine the deformed geometry of the mesostructure of the fabric, which in turn provides, through the constitutive relations, the internal nodal forces. In order to verify the accuracy of the elements, instrumented ballistic impact experiments with projectile velocities of 22–550 m/s were conducted on single layers of Kevlar ® fabric. Simulations of the experiments demonstrate that the finite elements are capable of efficiently simulating large, complex structures.

Spontaneous preterm birth is a frequent complication of pregnancy and a common cause of morbidity in childhood. Obstetricians suspect abnormalities of the cervix are implicated in a significant number of preterm births. The cervix is composed of fibrous connective tissue and undergoes significant remodeling in preparation for birth. We hypothesized that a tissue engineering strategy could be used to develop three-dimensional cervical-like tissue constructs that would be suitable for investigating cervical remodeling. Cervical cells were isolated from two premenopausal women undergoing hysterectomy for a benign gynecological condition, and the cells were seeded on porous silk scaffolds in the presence or absence of dynamic culture and with 10% or 20% serum. Morphological, biochemical, and mechanical properties were measured during the 8-week culture period. Cervical cells proliferated in three-dimensions and synthesized an extracellular matrix with biochemical constituents and morphology similar to native tissue. Compared to static culture, dynamic culture was associated with significantly increased collagen deposition (p

The split-Hopkinson pressure bar (SHPB) technique has been widely employed for over fifty years in characterizing the high strain-rate properties of many common engineering materials. Historically, however, this technique has had limited success in characterizing soft materials, since their low mechanical impedances can increase delays in attaining dynamic equilibrium and result in transmission pulses with extremely low signal-to-noise ratios. Due to interest in improving characterization of soft materials at high strain rates, numerous modifications to the traditional SHPB technique have been proposed. These include: using more sensitive piezoelectric gauges, employing hollow transmission bars, utilizing lower impedance polymeric pressure bars, and the use of pulse shaping techniques. To date, there has been no comparative studies or consensus within the SHPB community as to which approach is most advantageous. The goal of this investigation is to compare a number of these techniques, specifically the use of PMMA pressure bars and a hollow aluminum transmission bar (both with and without pulse shaping), alongside more traditional solid aluminum pressure bars in the characterization of polyurea, a common low impedance polymer. The advantages and disadvantages of each technique in generating high strain-rate stress-strain curves are discussed.

In normal pregnancy, the cervix maintains its shape during a period of substantial fetal and uterine growth. Hence, maintenance of biomechanical integrity is an important aspect of cervical function. It is known that cervical mechanical properties arise from the extracellular matrix. The most important constituent of the cervical extracellular matrix is fibrillar collagen – it is from collagen protein that the cervix derives its “strength.” Other matrix molecules known to affect the collagen network include water, proteoglycans, hyaluronan and elastin. The objective of this review is to discuss relationships between biochemical constituents and macroscopic mechanical properties. The individual constituents of the extracellular matrix will be discussed, especially in regard to collagen remodeling during pregnancy. In addition, the macroscopic mechanical properties of cervical tissue will be reviewed. An improved understanding of the biochemistry of cervical “strength” will shed light into how the cervix maintains its shape in normal pregnancy and shortens in preterm birth.

While it is recognized that the heterogeneous particles in HIPS play the dual role of providing multiple sites for craze initiation in the polystyrene (PS) matrix and allow the stabilization of the crazing process through cavitation/fibrillation in the PB phase within the particle, the precise role of particle morphology is not well understood or quantified. This work probes the micromechanics of uniaxial tensile deformation and failure in rubber-toughened PS through axi-symmetric finite element representative volume element (RVE) models that can guide the development of blends of optimal toughness. The RVE models reveal the effect on craze morphology and toughness by various factors such as particle compliance, particle morphology, particle fibrillation and particle volume fraction. The principal result of our study is that fibrillation/cavitation of PB domains within the heterogeneous particle provides the basic key ingredient to account for the micro- and macro-mechanics of HIPS.

Objective Although a short cervix is known to be associated with preterm birth, the patterns of three-dimensional, anatomic changes leading to a short cervix are unknown. Our objective was to (1) construct three-dimensional anatomic models during normal pregnancy and (2) use the models to compare cervical anatomy in the second and third trimester. Study design A cross-sectional study was performed in a population of patients referred to magnetic resonance imaging (MRI) for a fetal indication. Using magnetic resonance images for guidance, three-dimensional solid models of the following anatomic structures were constructed: amniotic cavity, uterine wall, cervical stroma, cervical mucosa and anterior vaginal wall. To compare cervical anatomy in the second and third trimester, models were matched according the size of the bony pelvis. Results Fourteen patients were imaged and divided into two groups according to gestational age: 20–24 weeks ( n =7)) and 31–36 weeks ( n =7). Compared to the second trimester, the third trimester was associated with significant descent of the amniotic sac ( p =.02). Descent of the amniotic sac was associated with modified anatomy of the uterocervical junction. These three-dimensional changes were associated with a cervix that appeared shorter in the third trimester. Conclusion We report a technique for constructing MRI-based, three-dimensional anatomic models during pregnancy. Compared to the second trimester, the third trimester is associated with three-dimensional changes in the cervix and lower uterine segment.

Current in vivo and in situ testing procedures are dominated by indentation. The major challenge for this testing technique is in finding a unique solution to the "inverse problem" i.e., defining an appropriate constitutive framework and obtaining material properties consistent with the indentation force-displacement data. Much of the information related to the interplay between shear and bulk compliance in the deformation field beneath the indenter is lost when capturing this single output. We propose a material testing method that follows the well proven path of conventional indentation methods, but enriches the signal by acquiring displacement data not only for the actuated indenter, but also for a set of offset, passive secondary sensors. We use finite element (FE) simulations involving three cases of materials: (a) linear elastic, (b) hyperelastic and (c) time-dependent to demonstrate the benefit of these additional sensors. The results indicate that the addition of these secondary sensors can help to discern between materials with varying degrees of compressibility.

We propose a new approach for developing continuum models for the mechanical behavior of woven fabrics in planar deformation. We generate a physically motivated continuum model that can both simulate existing fabrics and predict the behavior of novel fabrics based on the properties of the yarns and the weave. The approach relies on the selection of a geometric model for the fabric weave, coupled with constitutive models for the yarn behaviors. The fabric structural configuration is related to the macroscopic deformation through an energy minimization method, and is used to calculate the internal forces carried by the yarn families. The macroscopic stresses are determined from the internal forces using equilibrium arguments. Using this approach, we develop a model for plain weave ballistic fabrics, such as Kevlar®, based on a pin-joined beam geometry. We implement this model into the finite element code ABAQUS and simulate fabrics under different modes of deformation. We present comparisons between model predictions and experimental findings for quasi-static modes of in-plane loading.

The strain history dependence of the stress–strain behavior of thermoplastic vulcanizate (TPV) materials is studied through a set of experiments and micromechanical models. Thermoplastic vulcanizates are a class of composite material consisting of a high volume fraction of fully-cured elastomeric particles in a thermoplastic matrix. The stress–strain behavior of TPVs is found to soften after having been subjected to an initial load/unload cycle. In this paper, the TPV strain history dependence is experimentally documented on a representative TPV material (TPV-R) by subjecting TPV-R to load/unload/reload histories in plane strain compression to various magnitudes of strain. The stress–strain behavior is observed to be more compliant upon reloading, but the tangent modulus is found to increase with strain until the reloading stress–strain curve joins the initial curve. An increase in the magnitude of the initial strain excursion increases the compliance observed during reloading. The unloading behavior following the reload is very similar to the unloading behavior following the initial load. The underlying microscopic mechanisms which govern the strain history effects are investigated using micromechanical modelling of the composite structure and its deformation. The stress–strain behaviors predicted by the simulations are found to be in good agreement with the experimentally observed behavior over the entire strain history for each magnitude of strain considered. The models reveal the softening of the material to result from a reorganization of the particle/matrix microstructural configuration due to plastic stretching of interparticle ligaments during the initial load step followed by ligament bending and rotation during the unloading step. The new microstructural configuration that exists after the first load/unload cycle favors bending and rotation of the (now thinned) matrix ligaments (as opposed to plastic deformation of the ligaments) during reloading; the ligament bending and rotation occur under low stress levels which results in the more compliant response. The additional features of the stress–strain behavior during reloading are also captured well by the model.

The micromechanisms of deformation and recovery in thermoplastic vulcanizates (TPVs) are studied using a series of micromechanical models. TPVs are a class of composite material consisting of a relatively large volume fraction of elastomeric particles ( v p =0.40–0.90) in a thermoplastic matrix. A representative TPV with v p =0.77 is selected for the study. Six five-particle representative volume element (RVE) models are constructed where the symmetry of particle distribution and the relative thickness of the matrix ligament bridging particles are systematically varied. The macroscopic stress–strain behavior of the TPV during loading and unloading is successfully predicted by the simulation study as shown by direct comparison with experimental data. The simulation study reveals the important role of relative matrix ligament thickness as well as geometric asymmetry in the formation of a pseudo-continuous rubber phase which provides the rubber-like behavior of TPVs during loading. The study shows the important role of matrix ligament thickness in controlling the initial stiffness and flow stress of the TPV; thinner ligaments lead to earlier matrix yielding and thus earlier formation of the pseudo-continuous rubber phase. Upon formation of the pseudo-continuous rubber phase, the matrix material is seen to accommodate the large straining of the rubber phase by nearly rigid body motion (rotation and translation) of the bulky domains of the matrix; the rubber phase is seen to undergo large contortions as it attempts to deform as an almost continuous network around the “rigid” domains of matrix material. Furthermore, the asymmetry together with the thin matrix ligaments greatly aids the recovery of the material during unloading. Upon unloading, the rubber phase attempts recovery in a rubber-like manner. The bulkier regions of matrix material simply rotate and translate with the recovering rubber domains. The thin ligaments also rotate, but eventually also undergo bending and buckling which enables the large amount of recovery observed in thermoplastic vulcanizates.

The stress–strain behavior of thermoplastic vulcanizate (TPV) materials is studied experimentally; a constitutive model for the behavior is proposed and found to successfully predict the important features of the observed stress–strain behavior. TPVs are a relatively new class of elastomer-like material consisting of a rather high-volume fraction of elastomeric particles (0.40

Tooling cost is a major contributor to the total cost of small-lot production of sheet metal components. Within the framework of an academic/industrial/government partnership devoted to the development of a reconfigurable tool for stretch forming, we have implemented a Finite Element-based procedure to determine optimal die shape. In the reconfigurable forming tool (Hardt, D. E. et al., 1993, “A CAD Driven Flexible Forming System for Three-Dimensional Sheet Metal Parts,” Sheet Metal and Stamping Symp., Int. Congress and Exp., Detroit, MI, SAE Technical Paper Series 930282, pp. 69–76.), the die surface is created by the ends of an array of square pins, which can be individually repositioned by computer driven servo-mechanisms. An interpolating polymer layer is interposed between the part and the die surface to attain a smooth pressure distribution. The objective of the die design algorithm is to determine optimal positions for the pin array, which will result in the desired part shape. The proposed “spring-forward” method was originally developed for matched-die forming (Karafillis, A. P., and Boyce, M. C., 1992, “Tooling Design in Sheet Metal Forming using Springback Calculations,” Int. J. Mech. Sci., Vol. 34, pp. 113–131.; Karafillis, A. P., and Boyce, M. C., 1996, “Tooling And Binder Design for Sheet Metal Forming Processes Compensating Springback Error,” Int. J. Tools Manufac., Vol. 36, pp. 503–526.) and it is here extended and adapted to the reconfigurable tool geometry and stretch forming loading conditions. An essential prerequisite to the implementation of the die design procedure is the availability of an accurate FE model of the entire forming operation. The particular nature of the discrete die and issues related to the behavior of the interpolating layer introduce additional challenges. We have first simulated the process using a model that reproduces, as closely as possible, the actual geometry of the discrete tool. In order to optimize the delicate balance between model accuracy and computational requirements, we have then used the information gathered from the detailed analyses to develop an equivalent die model. An automated algorithm to construct the equivalent die model based on the discrete tool geometry (pin-positions) is integrated with the spring-forward method, to generate an iterative die design procedure that can be easily interfaced with the reconfiguring tool. The success of the proposed procedure in selecting an optimal die configuration is confirmed by comparison with experimental results.

A constitutive model for the finite deformation stress–strain behavior of poly(ethylene terephthalate) (PET) at temperatures above the glass transition temperature is presented. In this temperature regime, the behavior of PET is strongly dependent on strain rate and temperature; PET also experiences strain-induced crystallization at these temperatures. The constitutive model accounts for the rate and temperature dependence of the stress–strain behavior by modeling the competition between molecular orientation processes and molecular relaxation processes. The model is fully three-dimensional and is shown to be in good agreement with experimental data over a wide range in strain rates and temperatures as well as under both uniaxial compression and plane strain compression loading conditions.

Numerical studies are presented on micromechanical and macromechanical aspects of deformation mechanisms in toughened polycarbonate. The dependence of the macroscopic stress–strain behavior, and of the underlying patterns of matrix deformation, on void distribution and triaxiality of the loading conditions are discussed. The presence of voids is shown to create stress fields which favor shear yielding over brittle failure mechanisms and thus provide toughness even in the case of highly triaxial stress states. Additionally, we compare predictions obtained using a micromechanical model based on a traditional axisymmetric unit cell, with predictions obtained with an alternative model based on a staggered array of voids. The new model is an axisymmetric equivalent to the Voronoi tessellation of a Body Centered Cubic array of voids (V-BCC model). The V-BCC model appears to be able to better capture essential features of the mechanical behavior of the blends, and provides a more realistic cell-based representation of particle-filled materials in general.

An axisymmetric unit cell model based on a regular array of second-phase particles arranged on a BCC lattice is used to study deformation mechanisms of ferrite-pearlite structural steels. Microstructural characteristics of the steels were parameterized by the pearlite volume fraction, the aspect ratio of the pearlite particles, and the neighboring factor, which represents the ratio of interparticle spacing in the longitudinal direction to that in the transverse direction. FE analyses were carried out to investigate the macroscopic and microscopic response of unit cells with morphological features based on idealizations of the microstructures of the actual steels. Tensile properties of each constituent phase were obtained experimentally and used in the analyses. As compared to traditional axisymmetric models, the BCC cell model appears to be able to capture more realistically the behavior of the materials, and it accurately estimates the tensile behavior of the ferrite-pearlite steels even with a relatively large volume fraction of the pearlite phase. The effects of volume fraction and morphology of the second-phase particles on deformation behavior were also investigated.

Engineering artificial protein hydrogels for medical applications requires precise control over their mechanical properties, including stiffness, toughness, extensibility, and stability in the physiological environment. Here we demonstrate topological entanglement as an effective strategy to robustly increase the mechanical tunability of a transient hydrogel network based on coiled-coil interactions. Chain extension and entanglement are achieved by coupling the cysteine residues near the N- and C-termini, and the resulting chain distribution is found to agree with the Jacobson–Stockmayer theory. By exploiting the reversible nature of the disulfide bonds, the entanglement effect can be switched on and off by redox stimuli. With the presence of entanglements, hydrogels exhibit a 7.2-fold enhanced creep resistance and a suppressed erosion rate by a factor of 5.8, making the gels more mechanically stable in a physiologically relevant open system. While hardly affecting material stiffness (only resulting in a 1.5-fold increase in the plateau modulus), the entanglements remarkably lead to hydrogels with a toughness of 65 000 J m^(–3) and extensibility to approximately 3000% engineering strain, which enables the preparation of tough yet soft tissue simulants. This improvement in mechanical properties resembles that from double-network hydrogels but is achieved with the use of a single associating network and topological entanglement. Therefore, redox-triggered chain entanglement offers an effective approach for constructing mechanically enhanced and responsive injectable hydrogels.

Progesterone supplementation is recommended to prevent preterm birth in women with a short cervix, but the mechanism is unclear. We hypothesize that progesterone acts by altering the composition of the cervical extracellular matrix (ECM). We tested this hypothesis using human cervical fibroblasts in both two-dimensional (2D) and three-dimensional (3D) cultures. For 2D culture, cells were seeded in 6-well plates and cultured with media supplemented with estradiol (10(-8) M), progesterone (10(-7) or 10(-6) M), and vehicle. For 3D culture, the cells were cultured on a porous silk protein scaffold system. Progesterone and estrogen receptors were documented by immunohistochemistry and Western blot analysis. In both 2D and 3D cultures, decreased collagen synthesis was seen with increased progesterone concentration. Three-dimensional cultures could be maintained significantly longer than 2D cultures, and the morphology of 3D cultures appeared similar to native cervical tissue. Thus, further studies were performed in 3D culture. To determine the effect of progesterone concentration, the 3D scaffolds were cultured with estradiol (10(-8) M) and five conditions: vehicle; 10(-9), 10(-8), or 10(-7) M progesterone; or 10(-7) M progesterone plus 10(-6) M mifepristone. The highest progesterone concentration correlated with the least amount of collagen synthesis. Collagen synthesis progressively increased as progesterone concentration decreased. This effect was partially antagonized by mifepristone, suggesting the mechanism is mediated by the progesterone receptor. This hormonally responsive 3D culture system supports the hypothesis that progesterone has a direct effect on remodeling cervical ECM during pregnancy. The 3D culture system could be useful for studying the mechanism of progesterone effects on the cervix.

New therapies to prevent preterm birth are needed. Our objective was to study an injectable biomaterial for human cervical tissue as an alternative to cervical cerclage. Human cervical tissue specimens were obtained from premenopausal gynecological hysterectomies for benign indications. A 3-part biomaterial was formulated, consisting of silk protein solution blended with a 2-part polyethylene glycol gelation system. The solutions were injected into cervical tissue and the tissue was evaluated for mechanical properties, swelling, cytocompatibility, and histology. The stiffness of cervical tissue more than doubled after injection (P = .02). Swelling properties of injected tissue were no different than native tissue controls. Cervical fibroblasts remained viable for at least 48 hours when cultured on the biomaterial. We report a silk-based, biocompatible, injectable biomaterial that increased the stiffness of cervical tissue compared to uninjected controls. Animal studies are needed to assess this biomaterial in vivo.

High volume fraction aligned carbon nanotube (CNT) polymer nanocomposites (A-PNCs) are fabricated by biaxial mechanical densification of the CNTs, followed by polymer infiltration via capillarity-assisted wetting using an aerospace-grade epoxy. These A-PNCs are then tested in tension in order to determine the full constitutive relation of the material. Prior to this work, only bulk compression or nanomechanical tests have been attempted due to the small size of the samples. Elastic stiffness derived from optical strain mapping is in agreement both with prior experimental nanoindentation measurements and finite element calculations that include the effects of waviness of the reinforcing CNT ‘fibers’. Results from longitudinal and transverse testing are shown for 0, 4, and 6 % volume fraction CNT reinforcement, and imaging via scanning electron microscopy and micro-computed tomography is used to establish morphology. Future work includes tests to establish the shear modulus and complete the full constitutive relation as a function of CNT volume fraction.

Background We have previously demonstrated that valproic acid (VPA), a histone deacetylase inhibitor, can improve survival after hemorrhagic shock (HS), protect neurons from hypoxia-induced apoptosis, and attenuate the inflammatory response. We have also shown that administration of 6% hetastarch (Hextend [Hex]) after traumatic brain injury (TBI) decreases brain swelling, without affecting size of the lesion. This study was performed to determine whether addition of VPA to Hex would decrease the lesion size in a clinically relevant large animal model of TBI + HS. Methods Yorkshire swine (42-50 kg) were instrumented to measure hemodynamic parameters, intracranial pressure, and brain tissue oxygenation. A custom-designed, computer-controlled cortical impact device was used to create a TBI through a 20-mm craniotomy: 15-mm cylindrical tip impactor at 4-m/s velocity, 100-millisecond dwell time, and 12-mm penetration depth. Volume-controlled hemorrhage was started (40% blood volume) concurrent with the TBI. After 2 hours of shock, animals were randomized to one of three resuscitation groups (n = 7 per group) as follows: (1) isotonic sodium chloride solution; (2) 6% hetastarch, Hex; and (3) Hex and VPA 300 mg/kg (Hex + VPA). Volumes of Hex matched the shed blood, whereas that of the isotonic sodium chloride solution was three times the volume. VPA treatment was started after an hour of shock. After 6 hours of postresuscitation monitoring, brains were sectioned into 5-mm slices and stained with 2, 3, 5-Triphenyltetrazolium chloride to quantify the lesion size (mm) and brain swelling (percent change compared with uninjured side). Levels of acetylated histone H3 were determined to quantify acetylation, and myeloperoxidase and interleukine-1β (IL-1β) levels were measured as markers of brain inflammation. Results Combination of 40% blood loss with cortical impact and a period of shock (2 hours) and resuscitation resulted in a highly reproducible brain injury. Lesion size and brain swelling in the Hex + VPA group (1,989 [156.8] mm, and 19% [1.6%], respectively) were significantly smaller than the isotonic sodium chloride solution group (3,335 [287.9] mm and 36% [2.2%], respectively). Hex alone treatment significantly decreased the swelling (27% [1.6%]) without reducing the lesion size. The number of CD11b-positive cells as well as myeloperoxidase and IL-1 levels in the brains were significantly reduced by the VPA treatment. Conclusion In a combined HS and TBI model, treatment with artificial colloid (Hex) improves hemodynamic parameters and reduces swelling, without affecting the actual size of the brain lesion. Addition of VPA effectively reduces both the size of brain lesion and associated swelling by attenuating the inflammatory response.

Traumatic brain injury (TBI) to U.S. soldiers has become one of the most taxing consequences of IED attacks in OEF/OIF. This project has focused on investigations of traumatic injury to the brain caused by the primary effects of blast waves. The project combines clinical, experimental and modeling studies aimed at: (i) elucidating the cell and tissue-level mechanisms of injury produced by the effect of the blast wave, (ii) deriving associated blast injury criteria (metrics and thresholds), (iii) helping to identify and treat returnees suffering from TBI, and (iv) developing blast protection strategies for TBI mitigation.

Traumatic brain injury (TBI) and hemorrhagic shock (HS) are the leading causes of trauma-related mortality and morbidity. Combination of TBI and HS (TBI + HS) is highly lethal, and the optimal resuscitation strategy for this combined insult remains unclear. A critical limitation is the lack of suitable large animal models to test different treatment strategies. We have developed a clinically relevant large animal model of TBI + HS, which was used to evaluate the impact of different treatments on brain lesion size and associated edema. Yorkshire swine (42-50 kg) were instrumented to measure hemodynamic parameters and intracranial pressure. A computer-controlled cortical impact device was used to create a TBI through a 20-mm craniotomy: 15-mm cylindrical tip impactor at 4 m/s velocity, 100-ms dwell time, and 12-mm penetration depth. Volume-controlled hemorrhage was started (40% blood volume) concurrent with the TBI. After 2 h of shock, animals were randomized to one of three resuscitation groups (n = 5/group): (a) normal saline (NS); (b) 6% hetastarch, Hextend (Hex); and (c) fresh frozen plasma (FFP). Volumes of Hex and FFP matched the shed blood, whereas NS was three times the volume. After 6 h of postresuscitation monitoring, brains were sectioned into 5-mm slices and stained with TTC (2,3,5-triphenyltetrazolium chloride) to quantify the lesion size and brain swelling. Combination of 40% blood loss with cortical impact and a period of shock (2 h) resulted in a highly reproducible brain injury. Total fluid requirements were lower in the Hex and FFP groups. Lesion size and brain swelling in the FFP group (2,160 ± 202.63 mm and 22% ± 1.0%, respectively) were significantly smaller than those in the NS group (3,285 ± 130.8 mm3 and 37% ± 1.6%, respectively) (P < 0.05). Hex treatment decreased the swelling (29% ± 1.6%) without reducing the lesion size. Early administration of FFP reduces the size of brain lesion and associated swelling in a large animal model of TBI + HS. In contrast, artificial colloid (Hex) decreases swelling without reducing the actual size of the brain lesion.

OBJECTIVES The purpose of this study was to use a fixed reference to study movement (displacement) of the cervical internal os from the second to the third trimester in singletons and twins. The rationale was to gain insight into anatomic changes associated with cervical shortening. METHODS For each patient, 2 transperineal scans were performed 12 weeks apart (20 and 32 weeks). The internal os and symphysis pubis were visualized in the same field of view. Image registration techniques were used to align the 2 scans using the symphysis as a fixed reference. Total displacement, anterior displacement, and inferior displacement of the internal os were measured. Displacements were correlated with cervical shortening. Bland-Altman plots and interobserver intraclass correlation coefficients were calculated. RESULTS A total of 42 healthy participants were studied: 28 with singletons and 14 with twins. The mean ± SD values for total displacement were 2.1 ± 1.2 and 2.0 ± 1.2 cm for singletons and twins, respectively (P = .75). The direction of displacement was significantly different. The mean anterior displacement was 1.1 cm greater for singletons than for twins (95% confidence interval, 0.29-2.0 cm, P = .01). Mean inferior displacement was 1.3 cm greater for twins than for singletons (95% confidence interval, 2.2-0.1 cm; P = .03). Only inferior displacement correlated with cervical shortening (P < .001; R(2) = 0.74). For every 2.2 cm of inferior displacement, the cervix shortened 1.0 cm. Assessments of reliability showed good agreement between 2 observers. CONCLUSIONS The anatomic position of the internal cervical os depends on gestational age and fetal number. Cervical shortening correlated most strongly with inferior displacement.

The response of neural cells to mechanical cues is a critical component of the innate neuroprotective cascade aimed at minimizing the consequences of traumatic brain injury (TBI). Reactive gliosis and the formation of glial scars around the lesion site are among the processes triggered by TBI where mechanical stimuli play a central role. It is well established that the mechanical properties of the microenvironment influence phenotype and morphology in most cell types. It has been shown that astrocytes change morphology [1] and cytoskeletal content [2] when grown on substrates of varying stiffness, and that mechanically injured astrocyte cultures show alterations in cell stiffness [3]. Accurate estimates of the mechanical properties of central nervous system (CNS) cells in their in-vivo conditions are needed to develop multiscale models of TBI. Lu et al found astrocytes to be softer than neurons under small deformations [4]. In recent studies, we investigated the response of neurons to large strains and at different loading rates in order to develop single cell models capable of simulating cell deformations in regimes relevant for TBI conditions [5]. However, these studies have been conducted on cells cultured on hard substrates, and the measured cell properties might differ from their in-vivo counterparts due to the aforementioned effects. Here, in order to investigate the effects of substrate stiffness on the cell mechanical properties, we used atomic force microscopy (AFM) and confocal imaging techniques to characterize the response of primary neurons and astrocytes cultured on polyacrylamide (PAA) gels of varying composition. The use of artificial gels minimizes confounding effects associated with biopolymer gels (both protein-based and polysaccharide-based) where specific receptor bindings may trigger additional biochemical responses [1].Copyright © 2011 by ASME

We describe a modeling methodology intended as a preliminary step in the identification of appropriate constitutive frameworks for the time-dependent response of biological tissues. The modeling approach comprises a customizable rheological network of viscous and elastic elements governed by user-defined 1D constitutive relationships. The model parameters are identified by iterative nonlinear optimization, minimizing the error between experimental and model-predicted structural (load-displacement) tissue response under a specific mode of deformation. We demonstrate the use of this methodology by determining the minimal rheological arrangement, constitutive relationships, and model parameters for the structural response of various soft tissues, including ex vivo perfused porcine liver in indentation, ex vivo porcine brain cortical tissue in indentation, and ex vivo human cervical tissue in unconfined compression. Our results indicate that the identified rheological configurations provide good agreement with experimental data, including multiple constant strain rate load/unload tests and stress relaxation tests. Our experience suggests that the described modeling framework is an efficient tool for exploring a wide array of constitutive relationships and rheological arrangements, which can subsequently serve as a basis for 3D constitutive model development and finite-element implementations. The proposed approach can also be employed as a self-contained tool to obtain simplified 1D phenomenological models of the structural response of biological tissue to single-axis manipulations for applications in haptic technologies.

We have developed a general methodology, in the framework of the finite element method, for locally evaluating the generalized force acting on a material interface which is work-conjugate with the normal displacement of the interface itself. This methodology has been applied to the study of directional coarsening of γ′ precipitates in Ni-superalloys. The flexibility of the proposed method has allowed us to closely model the actual microstructural morphology of the alloys and to account for the effects of applied boundary conditions, lattice misfit, elastic anisotropy and inelastic behavior of the crystals. We have positively compared the indications of our model with available experimental data for a few alloys, and a circumscribed parametric study has lead us to formulate a more general interpretation of the rafting phenomenon, which appears to give a satisfactory explanation for all the available experimental observations.

This study presents experimental results and computational analysis of the large strain dynamic behavior of single neurons in vitro with the objective of formulating a novel quantitative framework for the biomechanics of cortical neurons. Relying on the atomic force microscopy (AFM) technique, novel testing protocols are developed to enable the characterization of neural soma deformability over a range of indentation rates spanning three orders of magnitude, 10, 1, and 0.1 μm s[superscript −1]. Modified spherical AFM probes were utilized to compress the cell bodies of neonatal rat cortical neurons in load, unload, reload and relaxation conditions. The cell response showed marked hysteretic features, strong non-linearities, and substantial time/rate dependencies. The rheological data were complemented with geometrical measurements of cell body morphology, i.e. cross-diameter and height estimates. A constitutive model, validated by the present experiments, is proposed to quantify the mechanical behavior of cortical neurons. The model aimed to correlate empirical findings with measurable degrees of (hyper)elastic resilience and viscosity at the cell level. The proposed formulation, predicated upon previous constitutive model developments undertaken at the cortical tissue level, was implemented in a three-dimensional finite element framework. The simulated cell response was calibrated to the experimental measurements under the selected test conditions, providing a novel single cell model that could form the basis for further refinements., Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies (DAAD-19-02-D-002), Joint Improvised Explosive Device Defeat Organization (U.S.) (W911NF-07-1-0035), National Science Foundation (U.S.). Graduate Research Fellowship, National Institutes of Health (U.S.) (Molecular, Cell, and Tissue Biomechanics Training Grant), Ecole des ponts et chaussees (France), Computation and Systems Biology Programme of Singapore--Massachusetts Institute of Technology Alliance

Objective. The purpose of this study was to develop a method to visualize 3-dimensional (3D) anatomic changes in the cervix and lower uterine segment during the antepartum period. Methods. An observational study of patients with both uncomplicated and complicated pregnancies was performed. To visualize 3D anatomic changes, solid models were constructed from 3D sonographic data. Model construction followed a 3-step protocol. First, 3D transvaginal sonographic data of the cervix and lower uterine segment were obtained. Second, sonographic data were exported to a medical image-processing program, which was used to align 3D sonographic data obtained from a single patient at different time points. Last, sonographic data were used to guide construction of solid models using mechanical design software. Anatomic changes were visualized by comparing solid models constructed from sonographic data obtained at different time points. Results. From 16 patients who consented, 5 patients were selected for this study Two to 4 models were derived from each of the 5 patients at 15 to 38 weeks' gestation. To show anatomic changes in the cervix and lower uterine segment, solid models from different time points in the same patient were superimposed. A total of 16 solid models were constructed. In addition, 3D changes associated with second-trimester cervical failure and successful therapeutic cerclage were shown. Conclusions. A method to visualize 3D cervical changes is presented, revealing complex anatomic changes in the lower uterine segment, cervical stroma, and cervical mucosa as pregnancy progresses.

In this paper, we show that bone piezoelectricity-a phenomenon in which bone polarizes electrically in response to an applied mechanical stress and produces a short-range electric field-may be a source of intense blast-induced electric fields in the brain, with magnitudes and timescales comparable to fields with known neurological effects. We compute the induced charge density in the skull from stress data on the skull from a finite-element full-head model simulation of a typical IED-scale blast wave incident on an unhelmeted human head as well as a human head protected by a kevlar helmet, and estimate the resulting electric fields in the brain in both cases to be on the order of 10 V/m in millisecond pulses. These fields are more than 10 times stronger than the IEEE safety guidelines for controlled environments (IEEE Standards Coordinating Committee 28, 2002) and comparable in strength and timescale to fields from repetitive Transcranial Magnetic Stimulation (rTMS) that are designed to induce neurological effects (Wagner et al., 2006a). They can be easily measured by RF antennas, and may provide the means to design a diagnostic tool that records a quantitative measure of the head's exposure to blast insult.

The cervix plays a crucial role in maintaining a healthy pregnancy, acting as a mechanical barrier to hold the fetus in utero during gestation. Altered mechanical properties of the cervical tissue are suspected to play a critical role in spontaneous preterm birth. Both MRI and X-ray data in the literature indicate that cervical stroma contains regions of preferentially aligned collagen fibers along anatomical directions (circumferential/longitudinal/radial). In this study, a mechanical testing protocol is developed to investigate the large-strain response of cervical tissue in uniaxial tension and compression along its three orthogonal anatomical directions. The stress response of the tissue along the different orthogonal directions is captured using a minimal set of model parameters generated by fitting a one-dimensional time-dependent rheological model to the experimental data. Using model parameters, mechanical responses can be compared between samples from patients with different obstetric backgrounds, between samples from different anatomical sites, and between the different loading directions for a single specimen. The results presented in this study suggest that cervical tissue is mechanically anisotropic with a uniaxial response dependent on the direction of loading, the anatomical site of the specimen, and the obstetric history of the patient. We hypothesize that the directionality of the tissue mechanical response is primarily due to collagen orientation in the cervical stroma, and provides an interpretation of our mechanical findings consistent with the literature data on preferential collagen alignment.

Traumatic brain injury (TBI) due to blast exposure is becoming increasingly prevalent in soldiers returning from war and some consider TBI to be the signature wound of the Iraq and Afghanistan conflicts [1]. Common causes are exposure to explosions of improvised explosive devices (IEDs), rocket-propelled grenades, and landmines. A study by Hoge et al found that of 2525 soldiers, 4.9% reported injuries with loss of consciousness and an additional 10.3% reported injuries with altered mental status [2]. Despite the prevalence of TBI, little is known on the epidemiology of mild TBI and on its long-term health consequences. An improved understanding of the damage mechanism and injury progression will be critical for designing better protective gear and selecting appropriate treatments.Copyright © 2009 by ASME

Understanding the mechanical response of brain tissue to dynamic loading conditions is critically needed for the development of realistic brain injury models. The characterization of the tissue behavior via mechanical testing and numerical modeling remains, however, challenging because of the strongly nonlinear time- and strain-dependencies inherent in the tissue response. While several studies [1–4] have uncovered some essential features of this response, the integration of all these features — nonlinearities, hysteresis, volumetric behavior — into one single constitutive framework remains an area of active research [5].Copyright © 2009 by ASME

Objective The cervix is the lower portion of the uterus. It is composed of fibrous tissue and its mechanical integrity is crucial for maintaining a healthy gestation. During normal pregnancy, the cervical extracellular matrix (ECM) remodels in preparation for labor. The objective of this study was to investigate the biochemical and morphological changes in cervical stroma associated with physiological remodeling during normal pregnancy. Study design Using human cervical tissue obtained from pregnant and non-pregnant patients, the ECM was analyzed for its biochemical constituents and histologic morphology. The ECM was assayed for hydration, collagen concentration, collagen solubility, total sulfated glycosaminoglycan concentration, and individual disaccharide concentration. The ECM morphology was visualized using conventional histological techniques (Masson's trichrome stain, polarized light microscopy) as well as second harmonic generation (SHG) imaging. Results When comparing pregnant to non-pregnant tissue, significant increases were measured for total sulfated glycosaminoglycans, hyaluronic acid, and collagen solubility. The microscopy studies confirmed that the collagenous network of the cervical stroma was anisotropic and pregnancy was associated with a discernable decrease in collagen organization. Conclusion Significant changes were seen in the concentration and organization of cervical ECM constituents during normal pregnancy.

We present a modular framework for mechanically regularized nonrigid image registration of 3D ultrasound and for identification of tissue mechanical parameters. Mechanically regularized deformation fields are computed from sparsely estimated local displacements. We enforce image-based local motion estimates by applying concentrated forces at mesh nodes of a mechanical finite-element model. The concentrated forces are generated by the elongation of regularization springs connected to the mesh nodes as their free ends are displaced according to local motion estimates. The regularization energy corresponding to the potential energy stored in the springs is minimized when the mechanical response of the model matches the observed response of the organ. We demonstrate that this technique is suitable for identification of material parameters of a nonlinear viscoelastic liver model and demonstrate its benefits over traditional indentation methods in terms of improved volumetric agreement between the model response and the experiment.

It has long been suggested that articular cartilage is susceptible to damage by repetitive mechanical loading (1–4); however, the exact mechanisms via which the damage is induced is not yet well-understood. As a step towards deeper understanding of damage, this work sought to address two main goals: (i) to investigate the consequences of subjecting initially intact cartilage to repeated long-term small-amplitude indentation loading that does not induce any observable damage over a short term; and (ii) to establish a 1-D nonlinear rheological model to capture the indentation response of the tissue in its “undamaged” and “damaged” states. Our objective is to use a simple model to provide a framework to interpret the changes in the macroscopic mechanical response in terms of alterations in its constituents properties.Copyright © 2007 by ASME

Computer-aided medical technologies are currently restricted by the limited understanding of the mechanical response of solid abdominal organs to finite loading conditions typical of surgical manipulation [5]. This limitation is a result of the difficulty in acquiring the necessary data on whole organs. To develop a constitutive model capable of predicting complex surgical scenarios, multiple testing modalities need to be simultaneously obtained to capture the fundamental nature of the tissue’s behavior under such conditions. In vivo tests are essential to obtain a realistic response, but their inherent difficulty and unknown boundary conditions makes them an impractical approach. Ex vivo tests are easy to control, but the response is unrealistic. A perfusion apparatus was previously developed that obtained near in vivo conditions for whole livers while allowing the ease of ex vivo testing [3]. This work presents the results from complete viscoelastic testing of whole-perfused livers with surgically relevant time-dependant indentation loading profiles to 35% nominal strain. These results will aid in the development of a constitutive model for the liver whose parameters can be related to the physical constituents of the tissue. As an intermediate modeling step, a 1D rheological modeling tool was used to identify the form and initial parameters for a constitutive model.Copyright © 2007 by ASME

The mechanical integrity of cervical tissue is crucial for maintaining a healthy gestation. Altered tissue biochemistry can cause drastic changes in the mechanical properties of the cervix and contribute to premature cervical dilation and delivery. We present an investigation of the mechanical and biochemical properties of cervical samples from human hysterectomy specimens. Three clinical cases were investigated: nonpregnant hysterectomy patients with previous vaginal deliveries; nonpregnant hysterectomy patients with no previous vaginal deliveries; and pregnant hysterectomy patients at time of cesarean section. Tissue samples were tested in confined compression, unconfined compression and tension. Cervical tissue samples for the three clinical cases were also subjected to biochemical analysis. Biochemical assays measured cervical tissue hydration, collagen content, collagen extractability and sulfated glycosaminoglycan (GAG) content. Results from the mechanical tests indicate that cervical stroma has a nonlinear, time-dependent stress response with varying degrees of conditioning and hysteresis depending on its obstetric background. It was found that the nonpregnant tissue was significantly stiffer than the pregnant tissue in both tension and compression. Further, collagen extractability, sulfated GAG content and hydration were substantially higher in the pregnant tissue. This study is the first important step towards the attainment of an improved understanding of the complex interplay between the molecular structure of cervical tissue and its macroscopic mechanical properties.