Introduction

The postnatal heart grows mostly in response to increased hemodynamic load. However, the specific biomechanical stimuli that stimulate cardiac growth as a reaction to increased hemodynamic load are still poorly understood. It has been shown that isolated neonatal rat cardiac myocytes normalize resting sarcomere length by adding sarcomeres in series when subjected to uniaxial static strain. Because there is experimental evidence that myocytes can distinguish the direction of stretch, it was postulated that myocytes also may normalize interfilament lattice spacing as a response to cross-fiber stretch.

Methods

A growth law was proposed in which fiber axial growth was stimulated by fiber strain deviating from zero and fiber radial growth by cross-fiber strain (parallel to the wall surface) deviating from zero. Fiber radial growth rate constant was 1/3 of the fiber axial growth rate constant. The growth law was implemented in a finite element model of the newborn Sprague-Dawley rat residually stressed left ventricle (LV). The LV was subjected to an end-diastolic pressure of 1 kPa and about 25 weeks of normal growth was simulated.

Results

Most cellular and chamber dimension changes in the model matched experimentally measured ones: LV cavity and wall volume increased from 2.3 and 54 μliter, respectively in the newborn to 276 μliter and 1.1 ml, respectively in the adult rat; LV shape became more spherical; internal LV radius increased faster than wall thickness; unloaded sarcomere lengths exhibited a transmural gradient. The major discrepancy with experiments included a reversed transmural gradient of cell length in the older rat.

Conclusion

A novel strain-based growth law has been presented that reproduced physiological postnatal growth in the rat LV.

Pulmonary arterial hypertension (PAH) is caused by narrowing and stiffening of the pulmonary arteries that increase pulmonary vascular impedance (PVZ). In particular, small arteries narrow and large arteries stiffen. Large pulmonary artery (PA) stiffness is the best current predictor of mortality from PAH. We have previously shown that collagen accumulation leads to extralobar PA stiffening at high strain (Ooi, Wang et al. 2010). We hypothesized that collagen accumulation would increase PVZ, including total pulmonary vascular resistance (Z0), characteristic impedance (ZC), pulse wave velocity (PWV), and index of global wave reflections (Pb/Pf), which contribute to increased right ventricular afterload. We tested this hypothesis by exposing mice unable to degrade type I collagen (Col1a1R/R) to 21 days of hypoxia (hypoxia), some of which were allowed to recover for 42 days (recovery). Littermate wild-type mice (Col1a1+/+) were used as controls. In response to hypoxia, mean PA pressure (mPAP) increased in both mouse genotypes with no changes in cardiac output (CO) or PA inner diameter (ID); as a consequence, Z0 (mPAP/CO) increased by ~100% in both genotypes (p<0.05). Contrary to our expectations, ZC, PWV and Pb/Pf did not change. However, with recovery, ZC and PWV decreased in the Col1a1+/+ mice and remained unchanged in the Col1a1R/R mice. Z0 decreased with recovery in both genotypes. Microcomputed tomography measurements of large PAs did not show evidence of stiffness changes as a function of hypoxia exposure or genotype. We conclude that hypoxia-induced PA collagen accumulation does not affect the pulsatile components of pulmonary hemodynamics but that excessive collagen accumulation does prevent normal hemodynamic recovery, which may have important consequences for right ventricular function.

Computational models have the potential to provide precise estimates of stresses and strains associated with sites of coronary plaque rupture. However, lack of adequate mathematical description of diseased human vessel wall mechanical properties is hindering computational accuracy. The goal of this study is to characterize the behavior of diseased human coronary and carotid arteries using planar biaxial testing. Diseased coronary specimens exhibit relatively high stiffness (50–210 kPa) and low extensibility (1–10%) at maximum equibiaxial stress (250 kPa) compared to human carotid specimens and values commonly reported for porcine coronary arteries. A thick neointimal layer observed histologically appears to be associated with heightened stiffness and the direction of anisotropy of the specimens. Fung, Choi-Vito and modified Mooney-Rivlin constitutive equations fit the multiaxial data from multiple stress protocols well, and parameters from representative coronary specimens were utilized in a finite element model with fluid-solid interactions. Computed locations of maximal stress and strain are substantially altered, and magnitudes of maximum principal stress (48–65 kPa) and strain (6.5–8%) in the vessel wall are lower than previously predicted using parameters from uniaxial tests. Taken together, the results demonstrate the importance of utilizing disease-matched multiaxial constitutive relationships within patient-specific computational models to accurately predict stress and strain within diseased coronary arteries.

In vivo human mitral valves (MV) were imaged using real-time 3D transesophageal echocardiography (rt-3DTEE), and volumetric images of the MV at mid-systole were analyzed by user-initialized segmentation and 3D deformable modeling with continuous medial representation, a compact representation of shape. The resulting MV models were loaded with physiologic pressures using finite element analysis (FEA). We present the regional leaflet stress distributions predicted in normal and diseased (regurgitant) MVs. Rt-3DTEE, semi-automated leaflet segmentation, 3D deformable modeling, and FEA modeling of the in vivo human MV is tenable and useful for evaluation of MV pathology.

The stiffness, anisotropy, and heterogeneity of freshly dissected (control) and perfusion-decellularized rat right ventricles were compared using an anisotropic inverse mechanics method. Cruciform tissue samples were speckled and then tested under a series of different biaxial loading configurations with simultaneous force measurement on all four arms and displacement mapping via image correlation. Based on the displacement and force data, the sample was segmented into piecewise homogeneous partitions. Tissue stiffness and anisotropy were characterized for each partition using a large-deformation extension of the general linear elastic model. The perfusion-decellularized tissue had significantly higher stiffness than the control, suggesting that the cellular contribution to stiffness, at least under the conditions used, was relatively small. Neither anisotropy nor heterogeneity (measured by the partition standard deviation of the modulus and anisotropy) varied significantly between control and decellularized samples. We thus conclude that although decellularization produces quantitative differences in modulus, decellularized tissue can provide a useful model of the native tissue extracellular matrix. Further, the large-deformation inverse method presented herein can be used to characterize complex soft tissue behaviors.

Biomechanical factors play fundamental roles in the natural history of abdominal aortic aneurysms (AAAs) and their responses to treatment. Advances during the past two decades have increased our understanding of the mechanics and biology of the human abdominal aorta and AAAs, yet there remains a pressing need for considerable new data and resulting patient-specific computational models that can better describe the current status of a lesion and better predict the evolution of lesion geometry, composition, and material properties and thereby improve interventional planning. In this paper, we briefly review data on the structure and function of the human abdominal aorta and aneurysmal wall, past models of the mechanics, and recent growth and remodeling models. We conclude by identifying open problems that we hope will motivate studies to improve our computational modeling and thus general understanding of AAAs.

Recent progress in tissue engineering has made it possible to build contractile bio-hybrid materials that undergo conformational changes by growing a layer of cardiac muscle on elastic polymeric membranes. Further development of such muscular thin films for building actuators and powering devices requires exploring several design parameters, which include the alignment of the cardiac myocytes and the thickness/Young’s modulus of elastomeric film. To more efficiently explore these design parameters, we propose a 3-D phenomenological constitutive model, which accounts for both the passive deformation including pre-stretch and the active behavior of the cardiomyocytes. The proposed 3-D constitutive model is implemented within a finite element framework, and can be used to improve the current design of bio-hybrid thin films and help developing bio-hybrid constructs capable of complex conformational changes.

The elastic modulus of bioengineered materials has a strong influence on the phenotype of many cells including cardiomyocytes. On polyacrylamide (PAA) gels that are laminated with ligands for integrins, cardiac myocytes develop well organized sarcomeres only when cultured on substrates with elastic moduli in the range of 10 kPa to 30 kPa, near those of the healthy tissue. On stiffer substrates (>60 kPa) approximating the damaged heart, myocytes form stress fiber-like filament bundles but lack organized sarcomeres or an elongated shape. On soft (<1 kPa) PAA gels myocytes exhibit disorganized actin networks and sarcomeres. However, when the polyacrylamide matrix is replaced by hyaluronic acid (HA) as the gel network to which integrin ligands are attached, robust development of functional neonatal rat ventricular myocytes occurs on gels with elastic moduli of 200 Pa, a stiffness far below that of the neonatal heart and on which myocytes would be amorphous and dysfunctional when cultured on polyacrylamide-based gels. The HA matrix by itself is not adhesive for myocytes, and the myocyte phenotype depends on the type of integrin ligand that is incorporated within the HA gel, with fibronectin, gelatin, or fibrinogen being more effective than collagen 1. These results show that HA alters the integrin-dependent stiffness response of cells in vitro and suggests that expression of HA within the extracellular matrix (ECM) in vivo might similarly alter the response of cells that bind the ECM through integrins. The integration of HA with integrin-specific ECM signaling proteins provides a rationale for engineering a new class of soft hybrid hydrogels that can be used in therapeutic strategies to reverse the remodeling of the injured myocardium.

Tissue assembly in the developing embryo is a rapid and complex process. While much research has focused on genetic regulatory machinery, understanding tissue level changes such as biomechanical remodeling remains a challenging experimental enigma. In the particular case of embryonic atrioventricular valves, micro-scale, amorphous cushions rapidly remodel into fibrous leaflets while simultaneously interacting with a demanding mechanical environment. In this study we employ two microscale mechanical measurement systems in conjunction with finite element analysis to quantify valve stiffening during valvulogenesis. The pipette aspiration technique is compared to a uniaxial load deformation, and the analytic expression for a uniaxially loaded bar is used to estimate the nonlinear material parameters of the experimental data. Effective modulus and strain energy density are analyzed as potential metrics for comparing mechanical stiffness. Avian atrioventricular valves from globular Hamburger–Hamilton stages HH25–HH34 were tested via the pipette method, while the planar HH36 leaflets were tested using the deformable post technique. Strain energy density between HH25 and HH34 septal leaflets increased 4.6±1.8 fold (±SD). The strain energy density of the HH36 septal leaflet was four orders of magnitude greater than the HH34 pipette result. Our results establish morphological thresholds for employing the micropipette aspiration and deformable post techniques for measuring uniaxial mechanical properties of embryonic tissues. Quantitative biomechanical analysis is an important and underserved complement to molecular and genetic experimentation of embryonic morphogenesis.

Simulation-based medicine and the development of complex computer models of biological structures is becoming ubiquitous for advancing biomedical engineering and clinical research. Finite element analysis (FEA) has been widely used in the last few decades to understand and predict biomechanical phenomena. Modeling and simulation approaches in biomechanics are highly interdisciplinary, involving novice and skilled developers in all areas of biomedical engineering and biology. While recent advances in model development and simulation platforms offer a wide range of tools to investigators, the decision making process during modeling and simulation has become more opaque. Hence, reliability of such models used for medical decision making and for driving multiscale analysis comes into question. Establishing guidelines for model development and dissemination is a daunting task, particularly with the complex and convoluted models used in FEA. Nonetheless, if better reporting can be established, researchers will have a better understanding of a model’s value and the potential for reusability through sharing will be bolstered. Thus, the goal of this document is to identify resources and considerate reporting parameters for FEA studies in biomechanics. These entail various levels of reporting parameters for model identification, model structure, simulation structure, verification, validation, and availability. While we recognize that it may not be possible to provide and detail all of the reporting considerations presented, it is possible to establish a level of confidence with selective use of these parameters. More detailed reporting, however, can establish an explicit outline of the decision-making process in simulation-based analysis for enhanced reproducibility, reusability, and sharing.

A new micro-computed tomography (μCT) image processing approach to estimate the loss of cement-bone interlock was developed using the concept that PMMA cement flows and cures around trabeculae during the total knee arthroplasty procedure. The initial mold shape of PMMA cement was used to estimate the amount of interdigitated bone at the time of implantation and following in vivo service using enbloc human postmortem retrievals. Laboratory prepared specimens, where there would be no biological bone resorption, were used as controls to validate the approach and estimate errors. The image processing technique consisted of identifying bone and cement from the μCT scan set, dilation of the cement to identify the cement cavity space, and Boolean operations to identify the different components of the interdigitated cement-bone regions. For laboratory prepared specimens, there were small errors in the estimated resorbed bone volume fraction (reBVfr = 0.11±0.09) and loss in contact area fraction (CAfr = 0.06±0.15). These values would be zero if there were no error in the method. For the postmortem specimens, the resorbed volume fraction (reBVfr = 0.85±0.16) was large, meaning that only 15% of the cement mold shape was still filled with bone. The loss of contact area fraction (CAfr = 0.84±0.17) was similarly large. This new approach provides a convenient method to visualize and quantify trabecular bone loss from interdigitated regions from postmortem retrievals. The technique also illustrates for the first time that there are dramatic changes in how bone is fixed to cement following in vivo service.

Intraluminal exposure of the infrarenal aorta to porcine pancreatic elastase represents one of the most commonly used experimental models of the development and progression of abdominal aortic aneurysms. Morphological and histological effects of elastase on the aortic wall have been well documented in multiple rodent models, but there has been little attention to the associated effects on mechanical properties. In this paper, we present the first biaxial mechanical data on, and associated nonlinear constitutive descriptors of, the effects of elastase on the infrarenal aorta in mice. Quantification of the dramatic, acute effects of elastase on wall behavior in vitro is an essential first step toward understanding the growth and remodeling of aneurysms in vivo, which depends on both the initial changes in the mechanics and the subsequent inflammation-mediated turnover of cells and extracellular matrix that contributes to the evolving mechanics.

Based on the hypothesis that diabetic foot lesions have a mechanical etiology, extensive efforts have sought to establish a relationship between ulcer occurrence and plantar pressure distribution. However, these factors are still not fully understood. The purpose of this study was to simultaneously record shear and pressure distributions in the heel and forefoot and to answer whether: (i) peak pressure and peak shear for anterior-posterior (AP) and medio-lateral (ML) occur at different locations, and if (ii) peak pressure is always centrally located between sites of maximum AP and ML shear stresses. A custom built system was used to collect shear and pressure data simultaneously on 11 subjects using the 2-step method. The peak pressure was found to be 362 kPa ±106 in the heel and 527 kPa ± 123 in the forefoot. In addition, the average peak shear values were higher in the forefoot than in the heel. The greatest shear on the plantar surface of the forefoot occurred in the anterior direction (mean and std dev: 37.7 ±7.6 kPa), whereas for the heel, peak shear on the foot was in the posterior direction (21.2 ±5 kPa). The results of this study suggest that the interactions of the shear forces caused greater “spreading” in the forefoot and greater tissue “dragging” in the heel. The results also showed that peak shear stresses do not occur at the same site or time as peak pressure. This may be an important factor in locating where skin breakdown occurs in patients at high-risk for ulceration.

Ascending stairs is a challenging activity of daily living for many populations. Frontal plane joint dynamics are critical to understand the mechanisms involved in stair ascension as they contribute to both propulsion and medio-lateral stability. However, previous research is limited to understanding these dynamics while initiating stair ascent from a stand. We investigated if initiating stair ascent from a walk with a comfortable self-selected speed could affect the frontal plane lower-extremity joint moments and powers as compared to initiating stair ascent from a stand and if this difference would exist at consecutive ipsilateral steps on the stairs. Kinematics data using a 3-D motion capture system and kinetics data using two force platforms on the first and third stair treads were recorded simultaneously as ten healthy young adults ascended a custom-built staircase. Data were collected from two starting conditions of stair ascent, from a walk (speed: 1.42±0.21m/s) and from a stand. Results showed that subjects generated greater peak knee abductor moment and greater peak hip abductor moment when initiating stair ascent from a walk. Greater peak joint moments and powers at all joints were also seen while ascending the second ipsilateral step. Particularly, greater peak hip abductor moment was needed to avoid contact of the contralateral limb with the intermediate step by counteracting the pelvic drop on the contralateral side. This could be important for therapists using stair climbing as a testing/training tool to evaluate hip strength in individuals with documented frontal plane abnormalities (i.e. knee and hip osteoarthritis, ACL injury).

We present a robust and computationally inexpensive method to estimate the lengths and three-dimensional moment arms for a large number of musculotendon actuators of the human lower limb. Using a musculoskeletal model of the lower extremity, a set of values was established for the length of each musculotendon actuator for different lower limb generalized coordinates (joint angles). A multidimensional spline function was then used to fit these data. Muscle moment arms were obtained by differentiating the musculotendon length spline function with respect to the generalized coordinate of interest. This new method was then compared to a previously used polynomial regression method. Compared to the polynomial regression method, the multidimensional spline method produced lower errors for estimating musculotendon lengths and moment arms throughout the whole generalized coordinate workspace. The fitting accuracy was also less affected by the number of dependent degrees of freedom and by the amount of experimental data available. The spline method only requires information on musculotendon lengths to estimate both musculotendon lengths and moment arms, thus relaxing data input requirements, whereas the polynomial regression requires different equations to be used for both musculotendon lengths and moment arms. Finally, we used the spline method in conjunction with an electromyography driven musculoskeletal model to estimate muscle forces under different contractile conditions, which showed the method is suitable for the integration into large scale neuromusculoskeletal models.

The hyoid bone is a unique bone in the skeleton not articulated to any other bone. The hyoid muscles, which attach to the hyoid bone, may play a role in neck mechanics, but analysis of their function requires quantifying hyoid bone mechanics. The goal of this study was to obtain the detailed kinematics of the hyoid bone over a large range of flexion-extension motion using radiographs at 5 postures. The position of the hyoid bone in the sagittal plane was characterized with respect to head, jaw and vertebral movements. Sex differences in hyoid kinematics were also investigated. We hypothesized that (1) the position of the hyoid bone in the sagittal plane is linearly correlated with motion of the head, jaw and vertebrae, and (2) the hyoid position, size and kinematics are sex-specific. We found that the hyoid bone X, Y and angular position generally had strong linear correlations with the positions of the head, jaw and the cervical vertebrae C1–C4. Hyoid X and angular position was also correlated to C5. Sex differences were found in some regressions of the hyoid bone with respect to C1–C5. The angular and linear measurements of the hyoid bone showed sex differences in absolute values, which were not evident after normalization by posture or neck size. Incorporating these results to neck models would enable accurate modeling of the hyoid muscles. This may have implications for analyzing the mechanics of the cervical spine, including loads on neck structures and implants.

Objectives

To develop an improved model representation of the biomechanics of the levator muscles during the second stage of labor and to use a sensitivity analysis to explore the pathomechanics of levator muscle injury.

Methods

A subject-specific finite element model of human pelvic floor and fetal head was developed based on in vivo MRI data of a fetal head and maternal pelvis. An anisotropic visco-hyperelastic constitutive model employed material parameters estimated from biaxial tests on pelvic floor tissues. Boundary conditions reflected both anatomic constraints and the curve of Carus. A short second stage of labor, scaled to 10 minutes, was then simulated using a single expulsive push made in the absence of levator co-contraction.

Results

Large levator stresses occured near the levator hiatus reaching 9 MPa at the pubovisceral muscle enthesis. The dominant principal stresses were located at, and aligned with, the edge of the hiatus. Muscle stretch bordering the levator hiatus was inhomogeneous: The average levator was 3.55 with a high of 4.64 at the pubovisceral muscle enthesis. Decreasing perineal body stiffness by 40%, 50%, and 60% led to reductions in the maximum principal stretch ratio at the pubovisceral muscle enthesis of 8%, 13%, and 18%, respectively.

Conclusions

The pubovisceral muscle enthesis and the muscle near the perineal body are the regions of greatest strain thereby placing them at highest risk for stretch-related injury. Decreasing perineal body tissue stiffness significantly reduced tissue stress and strain, and therefore injury risk, in those regions.

Cortical bone specimens were damaged using repeated blocks of tensile creep loading until a near-terminal amount of creep damage was generated (corresponding to a reduction in elastic modulus of 15%). One group of cortical bone specimens was submitted to the near-terminal damage protocol and subsequently underwent fatigue loading in tension with a maximum strain of 2000 με (Damage Fatigue, n=5). A second group was submitted to cyclic fatigue loading but was not pre-damaged (Control Fatigue, n=5). All but one specimen (a damaged specimen) reached run-out (10 million cycles, 7.7 days). No significant differences in microscopic cracks or other tissue damage were observed between the two groups or between either group and additional, completely unloaded specimens. Our results suggest that damage in cortical bone allograft that is not obvious or associated with a stress riser may not substantially affect its fatigue life under physiologic loading.

The Achilles’ tendon moment arm (ATma) is a critical quantity in that it defines the triceps surae’s ability to generate a moment on the calcaneus, which is then transferred to the foot. This measure has been primarily acquired two-dimensionally in small male populations. Thus, the primary purpose of this study was to establish the first in vivo three-dimensional measures of the ATma, measured non-invasively during dynamic activity in a large normative population, inclusive of both males and female subjects (n=20). Subjects were each placed supine in a 1.5T MRI and asked to repeat a simulated toe-raise while a full sagittal-cine-phase contrast (dynamic) MRI dataset was acquired. From these data, the 3D and 2D ATma was calculated. The ATma was scaled by the distal tibial width, based on a correlation analysis. The 2D ATma overestimated its 3D counterpart by 3.1 mm, on average. The scaled ATma was no different between the male and female cohorts, but the scaled Achilles’ tendon area was smaller in the male cohort. The magnitudes of the ATma were most similar to previously reported values when variations in ankle angle were taken into account. The results of this study have important implications for the applicability of ATma data to both clinical questions and modelling. Any future studies should adapt the ATma based on subject size and/or sex, ensure compatibility between the manner in which the ankle angle is defined and the data being used, and account for the influence that muscle force has on the 3D ATma.

Radial force (Fr) distributions describe grip force coordination about a cylindrical object. Recent studies have employed only explicit Fr tasks, and have not normalized for anatomical variance when considering Fr distributions. The goals of the present study were (i) to explore Fr during tangential force production tasks, and (ii) to examine the extent to which anatomical registration (i.e. spatial normalization of anatomically analogous structures) could improve signal detectability in Fr data. Twelve subjects grasped a vertically-oriented cylindrical handle (diameter = 6 cm) and matched target upward tangential forces of 10, 20, and 30 N. Fr data were measured using a flexible pressure mat with an angular resolution 4.8 deg, and were registered using piecewise-linear interpolation between five manually identified points-of-interest. Results indicate that Fr was primarily limited to three contact regions: the distal thumb, the distal fingers, and the fingers’ metatacarpal heads, and that, while increases in tangential force caused significant increases in Fr for these regions, they did not significantly affect the Fr distribution across the hand. Registration was found to substantially reduce between-subject variability, as indicated by both accentuated Fr trends, and amplification of the test statistic. These results imply that, while subjects focus Fr primarily on three anatomical regions during cylindrical grasp, inter-subject anatomical differences introduce a variability that, if not corrected for via registration, may compromise one’s ability to draw anatomically relevant conclusions from grasping force data.

Previous studies of the mechanical work performed during uphill and downhill walking have neglected the simultaneous negative and positive work performed by the leading and trailing legs during double support. Our goal was to quantify the mechanical work performed by the individual legs across a range of uphill and downhill grades. We hypothesized that during double support, 1) with steeper uphill grade, the negative work performed by the leading leg would become negligible and the trailing leg would perform progressively greater positive work to raise the center of mass (CoM), and 2) with steeper downhill grade, the leading leg would perform progressively greater negative work to lower the CoM and the positive work performed by the trailing leg would become negligible. 11 healthy young adults (6M/5F, 71.0 ± 12.3 kg) walked at 1.25 m/s on a dual-belt force-measuring treadmill at seven grades (0, ±3, ±6, ±9°). We collected three-dimensional ground reaction forces (GRFs) and used the individual limbs method to calculate the mechanical work performed by each leg. As hypothesized, the trailing leg performed progressively greater positive work with steeper uphill grade, and the leading leg performed progressively greater negative work with steeper downhill grade (p<0.005). To our surprise, unlike level-ground walking, during double support the leading leg performed considerable positive work when walking uphill and the trailing leg performed considerable negative work when walking downhill (p<0.005). To understand how humans walk uphill and downhill, it is important to consider these revealing biomechanical aspects of individual leg function and interaction during double support.

Aging is associated with loss of muscle volume (MV) and force leading to difficulties with activities of daily living. However, the relationship between upper limb MV and joint strength has not been characterized for older adults. Quantifying this relationship may help our understanding of the functional upper limb declines older adults experience. Our objective was to assess the relationship between upper limb MV and maximal isometric joint moment-generating capacity (IJM) in a single cohort of healthy older adults (age≥65 years) for 6 major functional groups (32 muscles). MV was determined from MRI for 18 participants (75.1±4.3 years). IJM at the shoulder (abduction/adduction), elbow (flexion/extension), and wrist (flexion/extension) was measured. MV and IJM measurements were compared to previous reports for young adults (28.6±4.5 years). On average older adults had 16.5% less total upper limb MV compared to young adults. Additionally, older adult wrist extensors composed a significantly increased percentage of upper limb MV. Older adult IJM was reduced across all joints, with significant differences for shoulder abductors (p<0.0001), adductors (p=0.01), and wrist flexors (p<0.0001). Young adults were strongest at the shoulder, which was not the case for older adults. In older adults, 40.6% of the variation in IJM was accounted for by MV changes (p≤0.027), compared to 81.0% in young adults. We conclude that for older adults, MV and IJM are, on average, reduced but the significant linear relationship between MV and IJM is maintained. These results suggest that older adult MV and IJM cannot be simply scaled from young adults.

Intervertebral disc degeneration, a leading cause of low back pain, poses a significant socioeconomic burden with a broad array of costly treatment options. Mechanical loading is important in disease progression and treatment. Connecting mechanics and biology is critical for determining how loading parameters affect cellular response and matrix homeostasis. A novel ex-vivo experimental platform was developed to facilitate in-situ loading of rabbit functional spinal units (FSUs) with relevant biological outcome measures. The system was designed for motion outside of an incubator and validated for rigid fixation and physiologic environmental conditions. Specimen motion relative to novel fixtures was assessed using a digitizer; fixture stiffness exceeded specimen stiffness by an order of magnitude. Intradiscal pressure (IDP), measured using a fiberoptic pressure transducer, confirmed rigidity and compressive force selection. Surrounding media was controlled at 37 °C, 5% O2/CO2 using a closed flow loop with an hypoxic incubator and was validated with probes in the specimen chamber. FSUs were subjected to cyclic compression (20 cycles) and four-hour creep at 1.0 MPa. Disc tissue was analyzed for cell viability using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), which showed high viability (> 90%) regardless of loading. Conditioned media was assayed for type-II collagen degradation fragments (CTX-II) and an aggrecan epitope (CS-846) associated with new aggrecan synthesis. CTX-II concentrations were not associated with loading, but CS-846 concentrations appeared to be increased with loading. Preservation of the full FSU allows physiologic load transmission and future multi-axis motion and identification of load-responsive proteins, thereby forming a new niche in intervertebral disc organ culture.

This work presents a validation of a fluid-structure interaction computational model simulating the flow conditions in an in vitro mock heart chamber modeling mitral valve regurgitation during the ejection phase during which the trans-valvular pressure drop and valve displacement are not as large. The mock heart chamber was developed to study the use of 2D and 3D color Doppler techniques in imaging the clinically relevant complex intra-cardiac flow events associated with mitral regurgitation. Computational models are expected to play an important role in supporting, refining, and reinforcing the emerging 3D echocardiographic applications. We have developed a 3D computational fluid-structure interaction algorithm based on a semi-implicit, monolithic method, combined with an arbitrary Lagrangian-Eulerian approach to capture the fluid domain motion. The mock regurgitant mitral valve corresponding to an elastic plate with a geometric orifice, was modeled using 3D elasticity, while the blood flow was modeled using the 3D Navier-Stokes equations for an incompressible, viscous fluid. The two are coupled via the kinematic and dynamic conditions describing the two-way coupling. The pressure, the flow rate, and orifice plate displacement were measured and compared with numerical simulation results. In-line flow meter was used to measure the flow, pressure transducers were used to measure the pressure, and a Doppler method developed by one of the authors was used to measure the axial displacement of the orifice plate. The maximum recorded difference between experiment and numerical simulation for the flow rate was 4%, the pressure 3.6%, and for the orifice displacement 15%, showing excellent agreement between the two.

Changes in the plantar soft tissue shear properties may contribute to ulceration in diabetic patients, however, little is known about these shear parameters. This study examines the elastic and viscoelastic shear behavior of both diabetic and non-diabetic plantar tissue. Previously compression tested plantar tissue specimens (n = 54) at six relevant plantar locations (hallux, first, third, and fifth metatarsal heads, lateral midfoot, and calcaneus) from four cadaveric diabetic feet and five non-diabetic feet were utilized. Per in vivo data (i.e., combined deformation patterns of compression followed by shear), an initial static compressive strain (36–38%) was applied to the tissue followed by target shear strains of 50% and 85% of initial thickness. Triangle waves were used to quantify elastic parameters at both strain levels and a stress relaxation test (0.25s ramp and 300s hold) was used to quantify the viscoelastic parameters at the upper strain level. Several differences were found between test groups including a 52–62% increase in peak shear stress, a 63% increase in toe shear modulus, a 47% increase in final shear modulus, and a 67% increase in middle slope magnitude (sharper drop in relaxation) in the diabetic tissue. Beyond a 54% greater peak compressive stress in the third metatarsal compared to the lateral midfoot, there were no differences in shear properties between plantar locations. Notably, this study demonstrates that plantar soft tissue with diabetes is stiffer than healthy tissue, thereby compromising its ability to dissipate shear stresses borne by the foot that may increase ulceration risk.