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The gastric biomechanics influences digestive function as well as a range of topics of medical and scientific interests such as interaction between the stomach and gastric devices. Hence, the mechanical properties are essential for understanding gastric tissue and function in health and disease, and for the development of diagnostic or therapeutic devices. A key characteristic to be characterized is the time dependent mechanical tissue properties. The aim of this study was to characterize viscoelastic properties of the stomach across a frequency range. Longitudinal and circumferential stomach samples from the porcine fundus, corpus and antrum were pre-stretched 10 % and sinusoidally loaded with 10 % dynamic strain. The viscoelastic properties were assessed from 0.01 − 15 Hz using dynamic mechanical analysis. The storage moduli, loss moduli and tan δ had a significant second-order polynomial trend with increasing frequency. For the loss moduli, significant differences were observed between 0.01 and 15 Hz and between 0.05 and 15 Hz (p = 0.023 to 0.041). Significant differences were not found for storage moduli. Tan δ was frequency-independent, indicating that the two moduli varied proportionally. Fundus had significantly smaller storage moduli for longitudinal samples compared to corpus (p = 0.034) and antrum (p = 0.014) but was not significantly different for circumferential samples. Analysis of direction-dependency showed significant differences between longitudinal and circumferential samples (p = 0.002 to 0.042). The presented work provides insight into tensile viscoelastic properties of gastric tissue, which is useful for developing biomaterials, devices and computational models for device development specification calibrations.

Allografts have become increasingly preferred for anterior cruciate ligament replacement purposes. The risk of infections necessitates thorough sterilization procedures, and the allografts usually need to be stored prior to surgery. Classical mechanical tests have been performed with various types of tendons, however, tibialis anterior and peroneus longus tend to suffer the least biomechanical changes after irradiation. Only few results are available of the strain and creep behaviour of tendons, even though this information is necessary to provide suitable allografts. The aim of the present study is to analyze the effect of different tendon types (T-tibialis anterior, P-peroneus longus), sterilization methods (G-gamma irradiation of 21 kGy, E-electron beam irradiation of 21 kGy) and storage times (5 and 6 months) on the creep behavior, which is characterized by the strain at the end of the loading phase and creep deformation after static loading. Static creep tests were performed with 250 N load during 60 s. Deformation at the end of the loading phase of both tendons was significantly smaller after 5 months long storage than that after 6 months long storage. TE5 showed significantly less creep than group TE6, and TE6 significantly greater than PE6. The creep of TE5 was significantly lower than that of TG5. Based on the data, the peroneus longus sterilized by electron beam and stored deep frozen for 5 months is a better choice for anterior cruciate ligament reconstruction than tibialis anterior sterilized by gamma irradiation stored for 6 months.

In this study, shear relaxation properties of the porcine temporomandibular joint (TMJ) disc are investigated. Previous studies have shown that, in fatigue failure and damage of cartilage and fibrocartilage, shear loads could be one of the biggest contributors to the failure. The aim of the present study is to develop an evaluation method to study shear properties of the disc and to do a mathematical characterization of it. For the experiments, twelve porcine discs were used. Each disc was dissected from the TMJ and, then, static strain control tests were carried out to obtain the shear relaxation modulus for the central region of the discs. From the results, it was found that the disc presents a viscoelastic behavior under shear loads. Relaxation modulus decreased with time. Shear relaxation was 10% of the instantaneous stress, which implies that the viscous properties of the disc cannot be neglected. The present results lead to a better understanding of the discs mechanical behavior under realistic TMJ working conditions.

To elucidate the process whereby sperm arrive at an egg in the female reproductive organs, it is essential to investigate how rheological properties of the fluid around mammalian spermatozoa affect their motility. We examined the motility and flagellar waveform of bovine sperm swimming in a fluid with similar rheological properties as mammalian cervical mucus. The results indicated that the surrounding rheological properties largely affected the flagellar waveform of mammalian spermatozoa; in particular, shear-thinning viscoelastic fluid increased the progressive motility of the sperm. To investigate the influence of flagellar waveform on sperm motility in more detail, the waveform was expressed as a function and the progressive thrust of the sperm was calculated based on the empirical resistive force theory. The results of this study showed that the progressive thrust increased with the curvature of the flagellar tip. Moreover, we calculated the thrust efficiency of motile sperm. Results showed that the thrust efficiency in shear-thinning viscoelastic fluids was larger than that in Newtonian fluids, regardless of viscosity. This suggests that motile sperm in cervical mucus move efficiently by means of a motion mechanism that is suited to their surrounding environment.

Vibratory function of the vocal folds is largely determined by the rheological properties or viscoelastic shear properties of the vocal fold lamina propria. To date, investigation of the sample size estimation and statistical experimental design for vocal fold rheological studies is nonexistent. The current work provides the closed-form sample size formulas for two major study designs (i.e. paired and two-group designs) in vocal fold research. Our results demonstrated that the paired design could greatly increase the statistical power compared to the two-group design. By comparing the variance of estimated treatment effect, this study also confirms that ignoring within-subject and within-vocal fold correlations during rheological data analysis will likely increase type I errors. Finally, viscoelastic shear properties of intact and scarred rabbit vocal fold lamina propria were measured and used to illustrate theoretical findings in a realistic scenario and project sample size requirement for future studies.

Mechanobiology plays an important role in tendon healing. However, the relationship between mechanical loading and spatial and temporal evolution of tendon properties during healing is not well understood. This study builds on a recently presented mechanoregulatory computational framework that couples mechanobiological tendon healing to tissue production and collagen orientation. In this study, we investigated how different magnitudes of mechanical stimulation (principal strain) affect the spatio-temporal evolution of tissue production and the temporal evolution of elastic and viscoelastic mechanical parameters. Specifically, we examined the effect of cell infiltration (mimicking migration and proliferation) in the callus on the resulting tissue production by modeling production to depend on local cell density. The model predictions were carefully compared with experimental data from Achilles tendons in rats, at 1, 2 and 4 weeks of healing. In the experiments, the rat tendons had been subjected to free cage activity or reduced load levels through intramuscular botox injections. The simulations that included cell infiltration and strain-regulated collagen production predicted spatio-temporal tissue distributions and mechanical properties similarly to that observed experimentally. In addition, lack of matrix-producing cells in the tendon core during early healing may result in reduced collagen content, regardless of the daily load level. This framework is the first to computationally investigate mechanobiological mechanisms underlying spatial and temporal variations during tendon healing for various magnitudes of loading. This framework will allow further characterization of biomechanical, biological, or mechanobiological processes underlying tendon healing.

© 2017 Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license: http://creativecommons.org/licenses/by-nc-nd/4.0/ This author accepted manuscript is made available following 12 month embargo from date of publication (Nov 2017) in accordance with the publisher’s archiving policy, Disc degeneration is a common medical affliction whose origins are not fully understood. An improved understanding of its underlying mechanisms could lead to the development of more effective treatments. The aim of this paper was to investigate the effect of (1) degeneration, (2) circumferential region and (3) strain rate on the microscale mechanical properties (toe region modulus, linear modulus, extensibility, phase angle) of individual fibre bundles in the anulus fibrosus lamellae of the human intervertebral disc. Healthy and degenerate fibre bundles excised from different circumferential regions in the outer anulus (posterolateral, lateral, anterolateral, anterior) were tensile tested at slow (0.1%/s), medium (1%/s) and fast (10%/s) strain rates using a micromechanical testing system. Our preliminary results showed that neither degeneration nor circumferential region significantly affected the fibre bundles’ mechanical behaviour. However, when the fibre bundles were tested at higher strain rates, this resulted in significantly higher linear moduli and lower phase angles. These findings, compared with data from other studies investigating single and multiple lamellae sections, suggest that degeneration has minimal effect on outer anulus mechanics irrespective of structural level, and the inter- and intra-lamellar arrangement and continuity of the fibre bundles may influence the lamellae’s regional behaviour and viscoelasticity.

Duchenne muscular dystrophy (DMD) is still an incurable muscle degenerative disease; thus, numerous studies focused on novel therapeutic approaches. However, a simple assay of muscle function restoration remains needed. Herein, we used an oscillatory shear rheometer to evaluate changes in rheological properties of mouse muscles (tibialis anterior, TA) and their restoration upon autologous cell therapy by comparing the viscoelastic properties of normal, diseased and treated muscles. Amplitude sweep tests of muscle samples were performed under 20% compression over a range of shear strain between 0.01 and 2% and frequency of 1 rad/s. The samples were tested in plane-plane geometry and horizontal myofiber alignment. Typical linear viscoelastic region (LVER) patterns were found for each muscle type. For healthy muscles, a broad LVER between shear deformations (γ) of 0.013–0.62% was observed. The LVER of DMD mdx/SCID muscles was found at 0.14% to 0.46% shear deformation, and no shear dependence of storage (G') and loss (G“) moduli at γ range changing from 0.034% to 0.26% was found for transplanted tissues. G'LVER and G”LVER moduli of healthy muscles were significantly higher than G'LVER and G“LVER of dystrophic tissues. Additionally, muscle resistance assessment by rheometer indicated that muscles transplanted with stem cells restored elastic properties to levels close to those of healthy muscles. Interestingly, histological staining and rheological data indicate that the loss factor is strongly related to structural changes of examined muscles.

Characterizing the viscoelastic behavior of neonatal peripheral nerves is critical in understanding stretch-related peripheral nerve injuries (PNIs) in neonates. This study investigated the in-vitro viscoelastic stress relaxation response of neonatal piglet brachial plexus (BP) and tibial nerves at two different strain levels (10% and 20%) and stress relaxation testing durations (90- and 300-seconds). BP and tibial nerves from 20 neonatal piglets were harvested and pre-stretched to either 10% or 20% strain at a dynamic rate of 100 mm/min to simulate conditions, such as shoulder dystocia, that may lead to stretch-related PNIs in neonates. At constant strain, the reduction in stress was recorded for 90- or 300-seconds. The biomechanical data were then fit to a viscoelastic model to acquire the short- and long-term stress relaxation time-constants. Though no significant differences in the degree of stress relaxation were found between the two tested strain levels after 90 seconds in both nerve types, reduction in stress was moderately greater (p = 0.056) at 10% strain than at 20% for BP after 300 seconds. The reduction in stress was significantly higher in nerves subjected to a 300 second testing duration than 90 second for both strain levels and nerve types. When comparing BP and tibial nerve stress relaxation response, BP nerve relaxed significantly more than tibial at both strain levels after 90 seconds, but no significant differences were observed after 300 seconds. Our results confirm that neonatal peripheral nerve tissue is highly viscoelastic. These novel biomechanical data can be incorporated into finite element and computational models studying neonatal PNIs.

Decellularised porcine super flexor tendon (pSFT) offers a promising solution to the replacement of damaged anterior cruciate ligament. It is desirable to package and terminally sterilise the acellular grafts to eliminate any possible harmful pathogens. However, irradiation techniques can damage the collagen structure and consequently reduce the mechanical properties. The aims of this study were to investigate the effects of irradiation sterilisation of varying dosages on the viscoelastic properties of the decellularised pSFT. Decellularised pSFT tendons were subjected to irradiation sterilisation using either 30 kGy gamma, 55 kGy gamma, 34 kGy E-beam, 15 kGy gamma, 15 kGy E-beam and (15 + 15) kGy E-beam (fractionated dose). Specimens then underwent stress relaxation testing at 0 and 12 months post sterilisation to determine whether any effect on the viscoelastic properties was progressive. Significant differences were found which demonstrated that all irradiation treatments had an effect on the time-independent and time-dependent viscoelastic properties of irradiated tendons compared to peracetic acid only treated controls. No significant differences were found between the irradiated groups and no significant differences were found between groups at 0 and 12 months. These results indicate the decellularised pSFT graft has a stable shelf-life.

Tendons transmit load from muscle to bone by utilizing their unique static and viscoelastic tensile properties. These properties are highly dependent on the composition and structure of the tissue matrix, including the collagen I hierarchy, proteoglycans, and water. While the role of matrix constituents in the tensile response has been studied, their role in compression, particularly in matrix pressurization via regulation of fluid flow, is not well understood. Injured or diseased tendons and tendon regions that naturally experience compression are known to have alterations in glycosaminoglycan content, which could modulate fluid flow and ultimately mechanical function. While recent theoretical studies have predicted tendon mechanics using poroelastic theory, no experimental data have directly demonstrated such behavior. In this study, we use high-bandwidth AFM-based rheology to determine the dynamic response of tendons to compressive loading at the nanoscale and to determine the presence of poroelastic behavior. Tendons are found to have significant characteristic dynamic relaxation behavior occurring at both low and high frequencies. Classic poroelastic behavior is observed, although we hypothesize that the full dynamic response is caused by a combination of flow-dependent poroelasticity as well as flow-independent viscoelasticity. Tendons also demonstrate regional dependence in their dynamic response, particularly near the junction of tendon and bone, suggesting that the structural and compositional heterogeneity in tendon may be responsible for regional poroelastic behavior. Overall, these experiments provide the foundation for understanding fluid-flow-dependent poroelastic mechanics of tendon, and the methodology is valuable for assessing changes in tendon matrix compressive behavior at the nanoscale. Keywords: Poroelasticity; Viscoelasticity; Tendon; AFM; Nanomechanics, National Institutes of Health (U.S.) (Grant F32-AG052284), National Science Foundation (U.S.) (Grant CMMI-1536233)

The mechanical environment and mechanobiology of bone marrow may play essential roles in bone adaptation, cancer metastasis, and immune cell regulation. However, the location of marrow within the trabecular pore space complicates experimental measurement of marrow mechanics. Computational models provide a means to assess the shear stress and pressure in the marrow during physiological loading, but they rely on accurate inputs for the marrow and the physics assumed for the interaction of bone and marrow. Elastic, viscoelastic, and fluid constitutive properties have all been reported from experimental measurements of marrow properties. It is unclear whether this ambiguity reflects the various length-scales, loading rates, and boundary conditions of the experiments, or if the material models are sufficiently similar as to be interchangeable. To address this question, we analyzed both the mean shear stress and its spatial distribution induced in marrow during compression of trabecular bone cubes when using linear elastic, neo-Hookean, viscoelastic, and power-law fluid constitutive models. Experimentally reported parameters were initially applied for all four constitutive models, resulting in poor agreement. The parameters of the soft solid models were calibrated by linear interpolation so that the volume averaged shear stress agreed with the fluid model for each, but this could only be accomplished on a specimen-by-specimen basis. Following calibration, the root-mean-squared (RMS) difference between the solid and fluid constitutive models was still greater than 26% even when the overall mean shear stress was in close agreement, indicating that the spatial distribution of stress is also sensitive to the constitutive model. As such, the choice of constitutive model should be backed by a strong rationale, and results should be interpreted with care.

Muscle force can be generated actively through changes in neural excitation, and passively through externally imposed changes in muscle length. Disease and injury can disrupt force generation, but it can be challenging to separate passive from active contributions to these changes. Ultrasound elastography is a promising tool for characterizing the mechanical properties of muscles and the forces that they generate. Most prior work using ultrasound elastography in muscle has focused on the group velocity of shear waves, which increases with increasing muscle force. Few studies have quantified the phase velocity, which depends on the viscoelastic properties of muscle. Since passive and active forces within muscle involve different structures for force transmission, we hypothesized that measures of phase velocity could detect changes in shear wave propagation during active and passive conditions that cannot be detected when considering only group velocity. We measured phase and group velocity in the human biceps brachii during active and passive force generation and quantified the differences in estimates of shear elasticity obtained from each of these measurements. We found that measures of group velocity consistently overestimate the shear elasticity of muscle. We used a Voigt model to characterize the phase velocity and found that the estimated time constant for the Voigt model provided a way to distinguish between passive and active force generation. Our results demonstrate that shear wave elastography can be used to distinguish between passive and active force generation when it is used to characterize the phase velocity of shear waves propagating in muscle.

The mitral valve is a highly heterogeneous tissue composed of two leaflets, anterior and posterior, whose unique composition and regional differences in material properties are essential to overall valve function. While mitral valve mechanics have been studied for many decades, traditional testing methods limit the spatial resolution of measurements and can be destructive. Optical coherence elastography (OCE) is an emerging method for measuring viscoelastic properties of tissues in a noninvasive, nondestructive manner. In this study, we employed air-pulse OCE to measure the spatial variation in mitral valve elastic properties with micro-scale resolution at 1 mm increments along the radial length of the leaflets. We analyzed differences between the leaflets, as well as between regions of the valve. We found that the anterior leaflet has a higher elastic wave velocity, which is reported as a surrogate for stiffness, than the posterior leaflet, most notably at the annular edge of the sample. In addition, we found a spatial elastic gradient in the anterior leaflet, where the annular edge was found to have a greater elastic wave velocity than the free edge. This gradient was less pronounced in the posterior leaflet. These patterns were confirmed using established uniaxial tensile testing methods. Overall, the anterior leaflet was stiffer and had greater heterogeneity in its mechanical properties than the posterior leaflet. This study measures differences between the two mitral leaflets with greater resolution than previously feasible and demonstrates a method that may be suitable for assessing valve mechanics following repair or during the engineering of synthetic valve replacements.

The Mechanical characterization of skeletal muscles is strongly dependent on numerous experimental design factors. Nevertheless, significant knowledge gaps remain on the characterization of muscle mechanics and a large number of experiments should be implemented to test the influence of a large number of factors. In this study, we propose a design of experiment method (DOE) to study the parameter sensitivity while minimizing the number of tests. A Box-Behnken design was then implemented to study the influence of strain rate, preconditioning and preloading conditions on visco-hyperelastic mechanical parameters of two rat forearm muscles. The results show that the strain rate affects the visco-hyperelastic parameters for both muscles. These results are consistent with previous work demonstrating that stiffness and viscoelastic contributions increase with strain rate. Thus, DOE has been shown to be a valid method to determine the effect of the experimental conditions on the mechanical behaviour of biological tissues such as skeletal muscle. This method considerably reduces the number of experiments. Indeed, the presented study using 3 parameters at 3 levels would have required at least 54 tests per muscle against 14 for the proposed DOE method.

It is well-accepted that articular (ART) cartilage composition and tissue architecture are intimately related to mechanical properties. On the other hand, very little information about other cartilage tissues is available, such as elastin-rich auricular (AUR) cartilage. While thorough investigation of ART cartilage has enhanced osteoarthritis research, ear cartilage reconstruction and tissue engineering (TE) could benefit in a similar way from in-depth analysis of AUR cartilage properties. This study aims to explore the constituent-function relationships of AUR cartilage, and how elastin influences mechanical behavior. Stress-relaxation indentation and tensile tests were performed on bovine ART and AUR cartilage. Elastase incubation was performed to simultaneously deplete elastin and sulfated glycosaminoglycans (sGAG), while hyaluronidase incubation was used to deplete sGAG-only, in order to systematically investigate matrix components in material behavior. ART and AUR cartilages showed different viscoelastic behaviors, with AUR cartilage exhibiting a more elastic behavior. Higher equilibrium properties and limited viscous dissipation of strain energy were observed in AUR cartilage, while ART cartilage exhibited a rapid viscous response and high resistance to instantaneous loading. In conclusion, loss of sGAG had no effect on auricular mechanics in contrast to articular cartilage where GAG loss clearly correlated with mechanical properties. Auricular cartilage without elastin lost all compressive mechanical integrity, whereas in articular cartilage this was provided by collagen. This work shows for the first time the involvement of elastin in the mechanical behavior of ear cartilage. In future, this data can be used in AUR cartilage TE efforts to support reproduction of tissue-specific mechanical properties. (C) 2015 Elsevier Ltd. All rights reserved.

Tendon’s viscoelastic behaviors are important to the mechanical function and mechanobiology. When loaded in longitudinal tension, tendons often have a very large Poisson’s ratio (ν > 2) that exceeds the limit of incompressibility for isotropic material (ν = 0.5), indicating that tendon experiences volume loss, inducing poroelastic fluid exudation in the transverse direction. Therefore, transverse poroelasticity is an important contributor to tendon material behavior. Tendon hydraulic permeability which is required to evaluate the fluid flow contribution to viscoelasticity, is mostly unavailable, and where available, varies by several orders of magnitude. In this manuscript, we quantified the transverse poroelastic material parameters of rat tail tendon fascicles by conducting transverse osmotic loading experiments, in both tension and compression. We used a multi-start optimization method to evaluate the parameters based on biphasic finite element modeling. Our tendon samples had a transverse hydraulic permeability of 10(−4) to 10(−5) mm(4) (Ns)(−1) and showed a significant tension-compression nonlinearity in the transverse direction. Further, using these results, we predict hydraulic permeability during longitudinal (fiber-aligned) tensile loading, and the spatial distribution of fluid flow during osmotic loading. These results reveal novel aspects of tendon mechanics and can be used to study the physiomechanical response of tendon in response to mechanical loading.

Stress generation during collective cell migration represents one of the key factors which influence the configuration of migrating cells, viscoelasticity of multicellular systems and their inter-relation. Local generation of stress (normal and shear) is significant even in 2D. Normal stress is primarily accumulated within a core region of migrating cell clusters during their movement through the dense environment and during the collisions of migrating cell clusters caused by uncorrelated motility. Shear stress can be significant within perturbed boundary layers around migrating clusters. Cells are more sensitive to the action of shear stress compared with normal stress. Shear stress of a few Pa significantly influences cell state. Prior studies have shown that collectively migrating cells move in such a way to minimize this stress, but it has not yet been determined how cells effectively minimize it. Deeper insight into possible cell mechanisms for minimizing undesirable shear stress would be of great importance because it may help to direct morphogenesis, accelerate wound healing or prevent cancer invasion. In the proposed model three primary mechanisms in which cells may reduce shear are given: decreasing speed, tissue thickening, and/or reducing slip effects. Suggestions obtained from the proposed model indicate a need for further experimental studies that will reveal whether the heterogeneity in the cell-cell adhesion types correlates well with the stiffness inhomogeneity, or changes in the adhesion clustering, cytoskeletal linkage or some other modification to the adhesion complex (adherens junctions or tight junctions) are occurring to influence overall adhesive strength.

Ultrasound elastography is envisioned as an optional modality to augment standard ultrasound B-mode imaging and is a promising technique to aid in detecting uterine masses which cause abnormal uterine bleeding in both pre- and post-menopausal women. In order to determine the effectiveness of strain imaging, mechanical testing to establish the elastic contrast between normal uterine tissue and stiffer masses such as leiomyomas (fibroids) and between softer pathologies such as uterine cancer and adenomyosis has to be performed. In this paper, we evaluate the stiffness of normal uterine tissue, leiomyomas, and endometrial cancers using a EnduraTEC ElectroForce (ELF) system. We quantify the viscoelastic characteristics of uterine tissue and associated pathologies globally by using two mechanical testing approaches, namely a dynamic and a quasi-static (ramp testing) approach. For dynamic testing, 21 samples obtained from 18 patients were tested. The testing frequencies were set to 1, 10, 20, and 30 Hz. We also report on stiffness variations with pre-compression from 1% to 6% for testing at 2%, 3%, and 4% strain amplitude. Our results show that human uterine tissue stiffness is both dependent on percent pre-compression and testing frequencies. For ramp testing, 20 samples obtained from 14 patients were used. A constant strain rate of 0.1% was applied and comparable results to dynamic testing were obtained. The mean modulus contrast at 2% amplitude between normal uterine tissue (the background) and leiomyomas was 2.29 and 2.17, and between the background and cancer was 0.47 and 0.39 for dynamic and ramp testing, respectively.

Trabecular bone is viscoelastic under dynamic loading. However, it is unclear how tissue viscoelasticity controls viscoelasticity at the apparent-level. In this study, viscoelasticity of cylindrical human trabecular bone samples (n = 11, male, age 18–78 years) from 11 proximal femurs were characterized using dynamic and stress-relaxation testing at the apparent-level and with creep nanoindentation at the tissue-level. In addition, bone tissue elasticity was determined using scanning acoustic microscope (SAM). Tissue composition and collagen crosslinks were assessed using Raman micro-spectroscopy and high performance liquid chromatography (HPLC), respectively. Values of material parameters were obtained from finite element (FE) models by optimizing tissue-level creep and apparent-level stress-relaxation to experimental nanoindentation and unconfined compression testing values, respectively, utilizing the second order Prony series to depict viscoelasticity. FE simulations showed that tissue-level equilibrium elastic modulus (Eeq) increased with increasing crystallinity (r = 0.730, p = .011) while at the apparent-level it increased with increasing hydroxylysyl pyridinoline content (r = 0.718, p = .019). In addition, the normalized shear modulus g1 (r = −0.780, p = .005) decreased with increasing collagen ratio (amide III/CH2) at the tissue-level, but increased (r = 0.696, p = .025) with increasing collagen ratio at the apparent-level. No significant relations were found between the measured or simulated viscoelastic parameters at the tissue- and apparent-levels nor were the parameters related to tissue elasticity determined with SAM. However, only Eeq, g2 and relaxation time τ1 from simulated viscoelastic values were statistically different between tissue- and apparent-levels (p < .01). These findings indicate that bone tissue viscoelasticity is affected by tissue composition but may not fully predict the macroscale viscoelasticity in human trabecular bone., final draft, peerReviewed

Ligaments and tendons undergo volume loss when stretched along the primary fiber axis, which is evident by the large, strain-dependent Poisson's ratios measured during quasi-static tensile tests. Continuum constitutive models that have been used to describe ligament material behavior generally assume incompressibility, which does not reflect the volumetric material behavior seen experimentally. We developed a strain energy equation that describes large, strain dependent Poisson's ratios and nonlinear, transversely isotropic behavior using a novel method to numerically enforce the desired volumetric behavior. The Cauchy stress and spatial elasticity tensors for this strain energy equation were derived and implemented in the FEBio finite element software (www.febio.org). As part of this objective, we derived the Cauchy stress and spatial elasticity tensors for a compressible transversely isotropic material, which to our knowledge have not appeared previously in the literature. Elastic simulations demonstrated that the model predicted the nonlinear, upwardly concave uniaxial stress-strain behavior while also predicting a strain-dependent Poisson's ratio. Biphasic simulations of stress relaxation predicted a large outward fluid flux and substantial relaxation of the peak stress. Thus, the results of this study demonstrate that the viscoelastic behavior of ligaments and tendons can be predicted by modeling fluid movement when combined with a large Poisson's ratio. Further, the constitutive framework provides the means for accurate simulations of ligament volumetric material behavior without the need to resort to micromechanical or homogenization methods, thus facilitating its use in large scale, whole joint models.

Voice is the essential part of singing and speech communication. Voice disorders significantly affect the quality of life. The viscoelastic mechanical properties of the vocal fold mucosa determine the characteristics of the vocal folds oscillations, and thereby voice quality. In the present study, a non-invasive method was developed to determine the shear modulus of human vocal fold tissue in vivo via measurements of the mucosal wave propagation speed during phonation. Images of four human subjects' vocal folds were captured using high speed digital imaging (HSDI) and magnetic resonance imaging (MRI) for different phonation pitches, specifically fundamental frequencies between 110 and 440 Hz. The MRI images were used to obtain the morphometric dimensions of each subject's vocal folds in order to determine the pixel size in the high-speed images. The mucosal wave propagation speed was determined for each subject and at each pitch value using an automated image processing algorithm. The transverse shear modulus of the vocal fold mucosa was then calculated from a surface (Rayleigh) wave propagation dispersion equation using the measured wave speeds. It was found that the mucosal wave propagation speed and therefore the shear modulus of the vocal fold tissue were generally greater at higher pitches. The results were in good agreement with those from other studies obtained via in vitro measurements, thereby supporting the validity of the proposed measurement method. This method offers the potential for in vivo clinical assessments of vocal folds viscoelasticity from HSDI.

We have studied stress relaxation of bovine femoral cortical bone specimens treated with KOH aqueous solution which had been known to degrade selectively protein molecules in bone. With the KOH treatment, we found an increase in specimens' volume. This increase was regarded as swelling of the bone specimen, presumably due to matrix protein network degradation including that of collagen. In an analogy of bone to gel structure, an increasing ratio of specimen volume was used as an indicating parameter for the matrix protein network degradation by the treatment. Although an empirical equation with a linearly combined form of two Kohlrausch-Williams-Watts (KWW) functions has been shown to describe the stress relaxation of bone specimens, a single KWW function was suitable for the bone specimens treated with KOH solution for as little as 3 h. In KOH treated specimens, both the initial modulus and the relaxation time decreased with the volume-increasing ratio, while the relaxation time distribution did not change. A chemo-rheological consideration attributed the reduction of modulus values to the network degradation in the organic matrix phase. The relaxation time of KOH treated specimens was thought to be related to the longer relaxation time of untreated bones, although there was a discontinuity between the extrapolated relaxation time values for KOH treated specimens and untreated specimens. This discontinuity may have originated from the release of residual stress existing in the bone by the matrix protein degradation. The results of the present study suggest that the state of matrix protein is crucial for integrating the mechanical properties of bone. (c) 2012 Elsevier Ltd. All rights reserved.

Permeability is an overarching mechanical parameter encompassing the effects of porosity, pore size, and interconnectivity of porous structures. This parameter directly influences transport of soluble particles and indirectly regulates fluid pressure and velocity in tissue engineering scaffolds. The permeability also contributes to the viscoelastic behavior of visco-porous material under loading through frictional drag mechanism. We propose a straightforward experimental method for permeability characterization of tissue engineering scaffolds. In the developed set-up a step-wise spacer was designed to facilitate measurement of the permeability under different compressive strains while maintaining similar experimental conditions during the successive measurements. As illustration of the method, we measured the permeability of scaffolds presenting different average pore sizes and subjected to different compression values. Results showed an exponential relationship between the permeability and the average pore size of the scaffolds. Furthermore, the trend of the permeability decrease with compressive strains was depending on pore sizes of the scaffolds. The permeability also appeared to play a role in relaxation behavior of the scaffolds.

Tendon functionality is related to its mechanical properties. Tendon damage leads to a reduction in mechanical strength and altered biomechanical behavior, and therefore leads to compromised ability to carry out normal functions such as joint movement and stabilization. Damage can also accumulate in the tissue and lead to failure. A noninvasive method with which to measure such damage potentially could quantify structural compromise from tendon injury and track improvement over time. In this study, tendon mechanics are measured before and after damage is induced by “overstretch” (strain exceeding the elastic limit of the tissue) using a traditional mechanical test system while ultrasonic echo intensity (average gray scale brightness in a B-mode image) is recorded using clinical ultrasound. The diffuse damage caused by overstretch lowered the stress at a given strain in the tissue and decreased viscoelastic response. Overstretch also lowered echo intensity changes during stress relaxation and cyclic testing. As the input strain during overstretch increased, stress levels and echo intensity changes decreased. Also, viscoelastic parameters and time-dependent echo intensity changes were reduced.

Creep is a time-dependent viscoelastic deformation observed under a constant prolonged load. It has been indicated that progressive vertebral deformation due to creep may increase the risk of vertebral fracture in the long-term. The objective of this study was to examine the relationships of creep with trabecular architecture and tissue mineral density (TMD) parameters in human vertebral cancellous bone at a physiological static strain level. Architecture and TMD parameters of cancellous bone were analyzed using microcomputerized tomography (micro-CT) in specimens cored out of human vertebrae. Then, creep and residual strains of the specimens were measured after a two-hour physiological compressive constant static loading and unloading cycle. Creep developed (3877 ± 2158 μe) resulting in substantial levels of non-recoverable post-creep residual strain (1797 ± 1391 μe). A strong positive linear correlation was found between creep and residual strain (r = 0.94, p < 0.001). The current results showed that smaller thickness, larger surface area, greater connectivity of trabeculae, less mean tissue mineral density (TMD, represented by gray levels) and higher variability of TMD are associated with increasing logarithmic creep rate. The TMD variability (GL(COV)) was the strongest correlate of creep rate (r = 0.79, p < 0.001). This result suggests that TMD variability may be a useful parameter for estimating the long-term deformation of a whole vertebral body. The results further suggest that the changes in TMD variability resulting from bone remodeling are of importance and may provide an insight into the understanding of the mechanisms underlying progressive failure of vertebral bodies and development of a clinical fracture.

Although stiffness and strength of lower limb bones have been investigated in the past, information is not complete. While the femur has been extensively investigated, little information is available about the strain distribution in the tibia, and the fibula has not been tested in vitro. This study aimed at improving the understanding of the biomechanics of lower limb bones by: (i) measuring the stiffness and strain distributions of the different low limb bones; (ii) assessing the effect of viscoelasticity in whole bones within a physiological range of strain-rates; (iii) assessing the difference in the behaviour in relation to opposite directions of bending and torsion. The structural stiffness and strain distribution of paired femurs, tibias and fibulas from two donors were measured. Each region investigated of each bone was instrumented with 8-16 triaxial strain gauges (over 600 grids in total). Each bone was subjected to 6-12 different loading configurations. Tests were replicated at two different loading speeds covering the physiological range of strain-rates. Viscoelasticity did not have any pronounced effect on the structural stiffness and strain distribution, in the physiological range of loading rates explored in this study. The stiffness and strain distribution varied greatly between bone segments, but also between directions of loading. Different stiffness and strain distributions were observed when opposite directions of torque or opposite directions of bending (in the same plane) were applied. To our knowledge, this study represents the most extensive collection of whole-bone biomechanical properties of lower limb bones.

Relaxation studies were conducted on specimens of bovine cancellous bone at post-yield strains. Stress and strain were measured for 1000s and the relaxation modulus was determined. Fifteen cylindrical, cancellous bone specimens were removed from one bovine femur in the anterior-posterior direction. The relaxation modulus was found to be a function of strain. Therefore cancellous bone is non-linearly viscoelastic/viscoplastic in the plastic region. A power law regression was fit to the relaxation modulus data. The multiplicative constant was found to be statistically related through a power law relationship to both strain (p0.0005) and apparent density (p0.0005) while the power coefficient was found to be related through a power law relationship, E(t, epsilon)=A(epsilon)t(-n(epsilon)), to strain (p0.0005), but not apparent density.

Udgivelsesdato: 2009-Aug-7 Orthopaedic implant fixation is strongly dependant upon the effective mechanical properties of newly formed tissue. In this study, we evaluated the potential of modal analysis to derive viscoelastic properties of periprosthetic tissue. We hypothesized that Young's modulus and loss factor could be obtained by a combined theoretical, computational and experimental modal analysis approach. This procedure was applied to ex vivo specimens from a cylindrical experimental implant placed in cancellous bone in an unloaded press-fit configuration, obtained after a four week observation period. Four sections each from seven textured titanium implants were investigated. The first resonant frequency and loss factor were measured. Average experimentally determined loss factor was 2% (SD 0.4%) and average first resonant frequency was 2.1 KHz (SD: 50). A 2D axisymmetric finite element (FE) model identified effective Young's modulus of tissue using experimental resonant frequencies as input. Average value was 42 MPa (SD: 2.4) and no significant difference between specimens was observed. In this pilot study, the non-destructive method allowed accurate measure of dynamic loss factor and resonant frequency and derivation of effective Young's modulus. Prior to implementing this dynamic protocol for broader mechanical evaluation of experimental implant fixation, further work is needed to determine if this affects results from subsequent destructive shear push-out tests.

The way in which the nucleus experiences mechanical forces has important implications for understanding mechanotransduction. Knowledge of nuclear material properties and, specifically, their relationship to the properties of the bulk cell can help determine if the nucleus directly experiences mechanical loads, or if it is a signal transduction mechanism secondary to cell membrane deformation that leads to altered gene expression. Prior work measuring nuclear material properties using micropipette aspiration suggests that the nucleus is substantially stiffer than the bulk cell [Guilak, F., Tedrow, J.R., Burgkart, R., 2000. Viscoelastic properties of the cell nucleus. Biochem. Biophys. Res. Commun. 269, 781-786], whereas recent work with unconfined compression of single chondrocytes showed a nearly one-to-one correlation between cellular and nuclear strains [Leipzig, N.D., Athanasiou, K.A., 2008. Static compression of single chondrocytes catabolically modifies single-cell gene expression. Biophys. J. 94, 2412-2422]. In this study, a linearly elastic finite element model of the cell with a nuclear inclusion was used to simulate the unconfined compression data. Cytoplasmic and nuclear stiffnesses were varied from 1 to 7 kPa for several combinations of cytoplasmic and nuclear Poisson's ratios. It was found that the experimental data were best fit when the ratio of cytoplasmic to nuclear stiffness was 1.4, and both cytoplasm and nucleus were modeled as incompressible. The cytoplasmic to nuclear stiffness ratio is significantly lower than prior reports for isolated nuclei. These results suggest that the nucleus may behave mechanically different in situ than when isolated.

A longstanding challenge in accurate mechanical characterization of engineered and biological tissues is maintenance of both stable sample hydration and high instrument signal resolution. Here, we describe the modification of an instrumented indenter to accommodate nanomechanical characterization of biological and synthetic tissues in liquid media, and demonstrate accurate acquisition of force–displacement data that can be used to extract viscoelastoplastic properties of hydrated gels and tissues. We demonstrate the validity of this approach via elastoplastic analysis of relatively stiff, water-insensitive materials of elastic moduli E41000 kPa (borosilicate glass and polypropylene), and then consider the viscoelastic response and representative mechanical properties of compliant, synthetic polymer hydrogels (polyacrylamide-based hydrogels of varying mol%-bis crosslinker) and biological tissues (porcine skin and liver) of Eo500 kPa. Indentation responses obtained via loading/unloading hystereses and contact creep loading were highly repeatable, and the inferred E were in good agreement with available macroscopic data for all samples. As expected, increased chemical crosslinking of polyacrylamide increased stiffness (Ep40 kPa) and decreased creep compliance. E of porcine liver (760 kPa) and skin (222 kPa) were also within the range of macroscopic measurements reported for a limited subset of species and disease states. These data show that instrumented indentation of fully immersed samples can be reliably applied for materials spanning several orders of magnitude in stiffness (E ¼ kPa–GPa). These capabilities are particularly important to materials design and characterization of macromolecules, cells, explanted tissues, and synthetic extracellular matrices as a function of spatial position, degree of hydration, or hydrolytic/enzymatic/corrosion reaction times.

Percutaneous implants are a family of devices that penetrate the skin and all suffer from the same problems of infection because the skin seal around the device is not optimal. Contributing to this problem is the mechanical discontinuity of the skin/device interface leading to stress concentrations and micro-trauma that chronically breaks any seal that forms. In this paper, we have quantified the mechanical behavior of human skin under low-magnitude shear loads over physiological relevant frequencies. Using a stress-controlled rheometer, we have performed isothermal (37 degrees C) frequency response experiments between 0.628 and 75.39 rad/s at 0.5% and 0.04% strain on whole skin and dermis-only, respectively. Step-stress experiments of 5 and 10 Pa shear loads were also conducted as were strain sweep tests (6.28 rad/s). Measurements were made of whole human skin and skin from which the epidermis was removed (dermis-only). At low frequencies (0.628-10 rad/s), the moduli are only slightly frequency dependent, with approximate power-law scaling of the moduli, G' approximately G'' approximately omega(beta), yielding beta=0.05 for whole skin and beta=0.16 for dermis-only samples. Step-stress experiments revealed three distinct phases. The intermediate phase included elastic "ringing" (damped oscillation) which provided new insights and could be fit to a mathematical model. Both the frequency and step-stress response data suggest that the epidermis provides an elastic rigidity and dermis provides viscoelasticity to the whole skin samples. Hence, whole skin exhibited strain hardening while the dermis-only demonstrated stress softening under step-stress conditions. The data obtained from the low-magnitude shear loads and frequencies that approximate the chronic mechanical environment of a percutaneous implant should aid in the design of a device with an improved skin seal.

In this paper we develop a lattice Boltzmann algorithm to simulate red blood cell (RBC) behavior in shear flows. The immersed boundary method is employed to incorporate the fluid-membrane interaction between the flow field and deformable cells. The cell membrane is treated as a neo-Hookean viscoelastic material and a Morse potential is adopted to model the intercellular interaction. Utilizing the available mechanical properties of RBCs, multiple cells have been studied in shear flows using a two-dimensional approximation. These cells aggregate and form a rouleau under the action of intercellular interaction. The equilibrium configuration is related to the interaction strength. The end cells exhibit concave shapes under weak interaction and convex shapes under strong interaction. In shear flows, such a rouleau-like aggregate will rotate or be separated, depending on the relative strengths of the intercellular interaction and hydrodynamic viscous forces. These behaviors are qualitatively similar to experimental observations and show the potential of this numerical scheme for future studies of blood flow in microvessels.

Despite continued progress in the treatment of aortic valve (AV) disease, current treatments continue to be challenged to consistently restore AV function for extended durations. Improved approaches for AV repair and replacement rests upon our ability to more fully comprehend and simulate AV function. While the elastic behavior the AV leaflet (AVL) has been previously investigated, time-dependent behaviors under physiological biaxial loading states have yet to be quantified. In the current study, we performed strain rate, creep, and stress-relaxation experiments using porcine AVL under planar biaxial stretch and loaded to physiological levels (60 N/m equi-biaxial tension), with strain rates ranging from quasi-static to physiologic. The resulting stress-strain responses were found to be independent of strain rate, as was the observed low level of hysteresis ( approximately 17%). Stress relaxation and creep results indicated that while the AVL exhibited significant stress relaxation, it exhibited negligible creep over the 3h test duration. These results are all in accordance with our previous findings for the mitral valve anterior leaflet (MVAL) [Grashow, J.S., Sacks, M.S., Liao, J., Yoganathan, A.P., 2006a. Planar biaxial creep and stress relaxatin of the mitral valve anterior leaflet. Annals of Biomedical Engineering 34 (10), 1509-1518; Grashow, J.S., Yoganathan, A.P., Sacks, M.S., 2006b. Biaxial stress-stretch behavior of the mitral valve anterior leaflet at physiologic strain rates. Annals of Biomedical Engineering 34 (2), 315-325], and support our observations that valvular tissues are functionally anisotropic, quasi-elastic biological materials. These results appear to be unique to valvular tissues, and indicate an ability to withstand loading without time-dependent effects under physiologic loading conditions. Based on a recent study that suggested valvular collagen fibrils are not intrinsically viscoelastic [Liao, J., Yang, L., Grashow, J., Sacks, M.S., 2007. The relation between collagen fibril kinematics and mechanical properties in the mitral valve anterior leaflet. Journal of Biomechanical Engineering 129 (1), 78-87], we speculate that the mechanisms underlying this quasi-elastic behavior may be attributed to inter-fibrillar structures unique to valvular tissues. These mechanisms are an important functional aspect of native valvular tissues, and are likely critical to improve our understanding of valvular disease and help guide the development of valvular tissue engineering and surgical repair.

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.

In this study, we proposed a novel approach to assess the energy dissipation during the post-yield deformation of bone. Based on the stress-strain behavior in an incremental and cyclic loading-unloading-reloading scheme in uniaxial tension, we partitioned the post-yield energy dissipation of bone into three distinct pathways: released elastic strain energy (U(er)); irreversible energy (U(i)); and hysteresis energy (U(h)). Among them, U(er) depends on the stiffness loss, U(i) is the energy permanently consumed, and U(h) reflects changes in the viscoelastic behavior of bone in the process of post-yield deformation. As an example, bone specimens from human cadaveric femurs of middle-aged and elderly donors were tested using this approach. The results of this study indicate that there exist age-related differences in post-yield energy dissipation and modulus degradation. These results implicate that this novel approach could detect the age-related differences in energy dissipation of bone and may aid in understanding the underlying mechanisms of such changes.

The fitting of quasi-linear viscoelastic (QLV) constitutive models to material data often involves somewhat cumbersome numerical convolution. A new approach to treating quasi-linearity in 1-D is described and applied to characterize the behavior of reconstituted collagen. This approach is based on a new principle for including nonlinearity and requires considerably less computation than other comparable models for both model calibration and response prediction, especially for smoothly applied stretching. Additionally, the approach allows relaxation to adapt with the strain history. The modeling approach is demonstrated through tests on pure reconstituted collagen. Sequences of "ramp-and-hold" stretching tests were applied to rectangular collagen specimens. The relaxation force data from the "hold" was used to calibrate a new "adaptive QLV model" and several models from literature, and the force data from the "ramp" was used to check the accuracy of model predictions. Additionally, the ability of the models to predict the force response on a reloading of the specimen was assessed. The "adaptive QLV model" based on this new approach predicts collagen behavior comparably to or better than existing models, with much less computation.

The purpose of this study was to gain an improved understanding of the mechanical behavior of the intervertebral disc in the presence and absence of the vertebral endplates. Mechanical behaviors of rat caudal motion segments, vertebrae and isolated disc explants under two different permeability conditions were investigated and viscoelastic behaviors were evaluated using a stretched-exponential function to describe creep and recovery behaviors. The results demonstrated that both vertebrae and discs underwent significant deformations in the motion segment even under relatively low-loading conditions. Secondly, disruption of the collagenous network had minimal impact on equilibrium deformations of disc explants as compared to disc deformations occurring in the motion segments provided that vertebral deformations were accounted for; however, differences in endplate permeability conditions had a significant effect on viscoelastic behaviors. Creep occurred more quickly than recovery for motion segment and explant specimens. In addition, disc explants and motion segments both exhibited non-recoverable deformations under axial compression under low- and high-loading conditions. Results have important implications for interpreting the role of vertebral endplates in contributing to disc mechanical behaviors and direct application to mechanobiology studies involving external loading to rodent tail intervertebral discs.

Stiffness degradation and strength degradation are often measured to monitor and characterize the effects of damage accumulation in bone. Based on evidence that these properties could be affected by not only damage magnitude but also test conditions, the present study investigated the effect of hold condition and recovery time on measures of tensile damage. Machined human femoral cortical bone specimens were subjected to tensile tests consisting of a pre-damage diagnostic loading cycle, a damage loading cycle and post-damage cycle. Controlled variables were recovery time (1, 10, and 100 min) and hold condition (zero load or zero strain) after the damage cycle. Damage measures were calculated as the ratio of each post-damage cycle to the pre-damage value for loading modulus, secant modulus, unloading modulus, stress relaxation and strain (stress) recovery at 1 min post-diagnostic time. The damage cycle caused reductions in all measures, and some measures varied with recovery time and hold condition. Apparent modulus degradation for both hold conditions decreased with recovery time. Stress relaxation was unaffected by recovery time for both hold conditions. Zero-strain hold conditions resulted in lower values for degradation of modulus and change of relaxation. Stress or strain recovery after the damage cycle was evident through 100 min, but 90% of the recovery occurred within 10 min. The results demonstrate that choice of test conditions can influence the apparent magnitude of damage effects. They also indicate that 10 min recovery time was sufficient to stabilize most measures of the damage state.

Discrete element models have often been the primary tool in investigating and characterising the viscoelastic behaviour of soft tissues. However, studies have employed varied configurations of these models, based on the choice of the number of elements and the utilised formation, for different subject tissues. This approach has yielded a diverse array of viscoelastic models in the literature, each seemingly resulting in different descriptions of viscoelastic constitutive behaviour and/or stress-relaxation and creep functions. Moreover, most studies do not apply a single discrete element model to characterise both stress-relaxation and creep behaviours of tissues. The underlying assumption for this disparity is the implicit perception that the viscoelasticity of soft tissues cannot be described by a universal behaviour or law, resulting in the lack of a unified approach in the literature based on discrete element representations. This paper derives the constitutive equation for different viscoelastic models applicable to soft tissues with two characteristic times. It demonstrates that all possible configurations exhibit a unified and universal behaviour, captured by a single constitutive relationship between stress, strain and time as: View the MathML source?+A??+B?¨=P??+Q?¨. The ensuing stress-relaxation G(t) and creep J(t ) functions are also unified and universal, derived as View the MathML sourceG(t)=c1e?A+A2?4B2Bt+(?0?c1)e?A?A2?4B2Bt and View the MathML sourceJ(t)=c2+(?0?c2)e-PQt+?0Pt, respectively. Application of these relationships to experimental data is illustrated for various tissues including the aortic valve, ligament and cerebral artery. The unified model presented in this paper may be applied to all tissues with two characteristic times, obviating the need for employing varied configurations of discrete element models in preliminary investigation of the viscoelastic behaviour of soft tissues.

Inverse finite element (FE) analysis is an effective method to predict material behavior, evaluate mechanical properties, and study differences in biological tissue function. The meniscus plays a key role in load distribution within the knee joint and meniscal degradation is commonly associated with the onset of osteoarthritis. In the current study, a novel transversely isotropic hyper-poro-viscoelastic constitutive formulation was incorporated in a FE model to evaluate changes in meniscal material properties following tibiofemoral joint impact. A non-linear optimization scheme was used to fit the model output to indentation relaxation experimental data. This study is the first to investigate rate of relaxation in healthy versus impacted menisci. Stiffness was found to be decreased (p=0.003), while the rate of tissue relaxation increased (p=0.010) at twelve weeks post impact. Total amount of relaxation, however, did not change in the impacted tissue (p=0.513).

The determination of subject-specific model parameter values is necessary in order for a computer simulation model of human motion to be evaluated quantitatively. This study used an optimisation procedure along with a kinematically driven simulation model of the contact phase in running jumps to determine the elastic parameters of segmental wobbling masses and the foot-ground interface. Kinetic and kinematic data were obtained on running jumps for height and distance performed by an elite male high jumper. Stiffness and damping coefficients of the visco-elastic elements in the model were varied until the difference between simulation and performance was minimised. Percentage differences of 6% and 9% between the simulated and recorded performances were obtained in the jumps for height and distance, respectively. When the parameters obtained from the jump for height were used in a simulation of the jump for distance (and vice versa), there was poor agreement with the recorded jump. On the other hand, a common set of visco-elastic parameters were obtained using the data from both recorded jumps resulting in a mean difference of only 8% (made up of 7% and 10%) between simulation and performance that was almost as good as the individual matches. Simulations were not overly sensitive to perturbations of the common set of visco-elastic parameters. It is concluded that subject-specific elastic parameters should be calculated from more than a single jump in order to provide a robust set of values that can be used in different simulations.

This study presents a framework for viscoelasticity where the free energy density depends on the stored energy of intact strong and weak bonds, where weak bonds break and reform in response to loading. The stress is evaluated by differentiating the free energy density with respect to the deformation gradient, similar to the conventional approach for hyperelasticity. The breaking and reformation of weak bonds is treated as a reaction governed by the axiom of mass balance, where the constitutive relation for the mass supply governs the bond kinetics. The evolving mass contents of these weak bonds serve as observable state variables. Weak bonds reform in an energy-free and stress-free state, therefore their reference configuration is given by the current configuration at the time of their reformation. A principal advantage of this formulation is the availability of a strain energy density function that depends only on observable state variables, also allowing for a separation of the contributions of strong and weak bonds. The Clausius–Duhem inequality is satisfied by requiring that the net free energy from all breaking bonds must be decreasing at all times. In the limit of infinitesimal strains, linear stress–strain responses and first-order kinetics for breaking and reforming of weak bonds, the reactive framework reduces exactly to classical linear viscoelasticity. For large strains, the reactive and classical quasilinear viscoelasticity theories produce different equations, though responses to standard loading configurations behave similarly. This formulation complements existing tools for modeling the nonlinear viscoelastic response of biological soft tissues under large deformations.

The mechanical contribution of nucleus in adherent cells to bearing intracellular stresses remains unclear. In this paper, the effects of fluid shear stress on morphology and elastic properties of endothelial nuclei were investigated. The morphological observation suggested that the nuclei in the cytoplasm were being vertically compressed under static conditions, whereas they were elongated and more compressed with a fluid shear stress of 2 Pa (20 dyn/cm(2)) onto the cell. The elongated nuclei remained the shape even after they were isolated from the cells. The micropipette aspiration technique on the isolated nuclei revealed that the elastic modulus of elongated nuclei, 0.62 +/- 0.15 kPa (n = 13, mean +/- SD), was significantly higher than that of control nuclei, 0.42 +/- 0.12 kPa (n = 11), suggesting that the nuclei remodeled their structure due to the shear stress. Based of these results and a transmission electron microscopy, a possibility of the nucleus as an intracellular compression-bearing organelle was proposed, which will impact interpretation of stress distribution in adherent cells. (C) 2005 Elsevier Ltd. All rights reserved.

Brainstem trauma occurs frequently in severe head injury, often resulting in fatal lesions due to importance of brainstem in crucial neural functions. Structurally, the brainstem is composed of bundles of axonal fibers distinctly oriented in a longitudinal direction surrounded by an extracellular matrix. We hypothesize that the oriented structure and architecture of the brainstem dictates this mechanical response and results in its selective vulnerability in rotational loading. In order to understand the relationship between the biologic architecture and the mechanical response and provide further insight into the high vulnerability of this region, a structural and mathematical model was created. A fiber-reinforced composite model composed of viscoelastic fibers surrounded by a viscoelastic matrix was used to relate the biological architecture of the brainstem to its anisotropic mechanical response. Relevant model parameters measured include the brainstem's composite complex moduli and relative fraction of matrix and fiber. The model predicted that the fiber component is three times stiffer and more viscous than the matrix. The fiber modulus predictions were compared with experimental tissue measurements. The optic nerve, a bundle of tightly packed longitudinally arranged myelinated fibers with little matrix, served as a surrogate for the brainstem fiber component. Model predictions agreed with experimental measures, offering a validation of the model. This approach provided an understanding of the relationship between the specific biologic architecture of the brainstem and the anisotropic mechanical response and allowed insight into reasons for the selective vulnerability of this region in rotational head injury.

Traumatic damage to the brainstem occurs frequently when the brain skull complex experiences injurious loading especially during those traumatic situations that produce diffuse axonal injury (DAI). DAI has been shown to be dependent on load direction and correlated with regional tissue deformation in response to rotational inertial loads. Possible mechanisms for the selective vulnerability of the brainstem are (1) the geometry of the central nervous system is responsible for producing high tissue strains in these regions, (2) regional differences in overall material stiffness result in larger deformations at these sites, and (3) the anisotropic mechanical properties of these regions lead to a sensitivity to the rotational load direction and magnitude. This paper investigates the latter two hypotheses by performing oscillatory shear tests on adult porcine brainstem in three mutually perpendicular directions. The complex shear moduli were calculated over a range of frequencies (20-200 Hz), for three levels of peak engineering strain (2.5%, 5.0%, and 7.5%). The directional data demonstrated that the brainstem exhibits significant transversely isotropic behavior. Both components of the complex modulus in which the axonal fibers are oriented parallel to the plane of shear but transverse to the shear direction were significantly higher than those of the other two, mutually indistinguishable test cases across the range of strains tested. By comparison with similar tests on cerebral tissue, these data demonstrated that the brainstem displays a stiffer biomechanical response. These differences were present for both components of the complex shear modulus and were greater as the magnitude of the applied strain increased. The regional stiffness and anisotropic response of the brainstem coupled with its location as a narrow bridge between CNS regions interact to result in the selective vulnerability of this region in rotational loading.

Traction tests on soft tissues show that the shape of the stress strain curves depends on the strain rate at which the tests are performed. Many of the constitutive models that have been proposed fail to properly consider the effect of the strain rate when large deformations are encountered. In the present study, a framework based on elastic and viscous potentials is developed. The resulting constitutive law is valid for large deformations and satisfies the principles of thermodynamics. Three parameters -- two for the elasticity and one for the viscosity -- were enough to precisely fit the non-linear stress strain curves obtained at different strain rates with human cruciate ligaments and patellar tendons. The identification results then in a realistic, three-dimensional viscoelastic constitutive law. The developed constitutive law can be used regardless of the strain or rotation values. It can be incorporated into a finite element program to model the viscoelastic behavior of ligaments and tendons under dynamic situations.

Under tensile loading, tendon undergoes a number of unique structural changes that govern its mechanical response. For example, stretching a tendon is known to induce both the progressive “uncrimping” of wavy collagen fibrils and extensive lateral contraction mediated by fluid flow out of the tissue. However, it is not known whether these processes are interdependent. Moreover, the rate-dependence of collagen uncrimping and its contribution to tendon's viscoelastic mechanical properties are unknown. Therefore, the objective of this study was to (a) develop a methodology allowing for simultaneous measurement of crimp, stress, axial strain and lateral contraction in tendon under dynamic loading; (b) determine the interdependence of collagen uncrimping and lateral contraction by testing tendons in different swelling conditions; and (c) assess how the process of collagen uncrimping depends on loading rate. Murine flexor carpi ulnaris (FCU) tendons in varying ionic environments were dynamically stretched to a set strain level and imaged through a plane polariscope with the polarizer and analyzer at a fixed angle. Analysis of the resulting images allowed for direct measurement of the crimp frequency and indirect measurement of the tendon thickness. Our findings demonstrate that collagen uncrimping and lateral contraction can occur independently and interstitial fluid impacts tendon mechanics directly. Furthermore, tensile stress, transverse contraction and degree of collagen uncrimping were all rate-dependent, suggesting that collagen uncrimping plays a role in tendon's dynamic mechanical response. This study is the first to characterize the time-dependence of collagen uncrimping in tendon, and establishes structure–function relationships for healthy tendons that can be used to better understand and assess changes in tendon mechanics after disease or injury.

Characterization of the dynamic mechanical behavior of brain tissue is essential for understanding and simulating the mechanisms of traumatic brain injury (TBI). Changes in mechanical properties may also reflect changes in the brain due to aging or disease. In this study, we used magnetic resonance elastography (MRE) to measure the viscoelastic properties of ferret brain tissue in vivo. Three-dimensional (3D) displacement fields were acquired during wave propagation in the brain induced by harmonic excitation of the skull at 400 Hz, 600 Hz and 800 Hz. Shear waves with wavelengths on the order of millimeters were clearly visible in the displacement field, in strain fields, and in the curl of displacement field (which contains no contributions from longitudinal waves). Viscoelastic parameters (storage and loss moduli) governing dynamic shear deformation were estimated in gray and white matter for these excitation frequencies. To characterize the reproducibility of measurements, two ferrets were studied on three different dates each. Estimated viscoelastic properties of white matter in the ferret brain were generally similar to those of gray matter and consistent between animals and scan dates. In both tissue types G′ increased from approximately 3 kPa at 400 Hz to 7 kPa at 800 Hz and G″ increased from approximately 1 kPa at 400 Hz to 2 kPa at 800 Hz. These measurements of shear wave propagation in the ferret brain can be used to both parameterize and validate finite element models of brain biomechanics.