bluuebunny/crossref_metadata_2025 huggingface dataset:
Engineered MSC-Laden Cartilage Constructs are Sensitive to Inflammatory Cytokine-Mediated Degradation
Authors: Yeger-McKeever Meira , Huang Alice H. , Stein Ashley F. , Mauck Robert L.
Published: March 2014

Degeneration of cartilage resulting from trauma or disease processes is an increasingly prevalent problem in the aging population. Intrinsic repair of cartilage is limited and few methodologies exist, short of prosthetic replacement, for restoring damaged articular surfaces. These realities engender a need for new strategies for extrinsic repair. One strategy, tissue engineering, generates replacement cartilage composed of scaffolds and differentiated chondrocytes [1]. In addition to chondrocytes, recent work has demonstrated that mesenchymal stem cells (MSCs) isolated from bone marrow may be induced to take on a chondrocyte-like phenotype [2]. Tissue engineered constructs of either cell type can yield near-native properties (though those derived from MSCs are typically lower) [3]. While such constructs may be surgically implanted to replace areas denuded of cartilage, one factor to consider is that these defect sites exist in an already inflamed joint [4]. In addition, surgical interventions trigger further inflammatory responses, greatest in the area of intervention [5]. Recent literature has shown that pro-inflammatory cytokines, such as interleukin-1beta (IL-1β), instigate catabolic destruction not only of cartilage explants, but also of chondrocyte-based engineered cartilage constructs [6–9]. Still other studies have shown that un-differentiated MSCs themselves may exert an anti-inflammatory effect on their local environment [10–12]. Thus the current study examined the effect of varying doses of IL-1β exposure on both chondrocyte- and MSC-based engineered cartilage constructs to determine the relative sensitivity of neo-cartilage derived from each cell type to cytokine induced degradation.
Vascular Smooth Muscle Cell Mechanics During Cyclic Stretch: Effect of Serum and a Serum Substitute
Authors: Du Wei , Pryse Kenneth M. , Fee Judy A. , Elson Elliot L. , Okamoto Ruth J.
Published: March 2014

Remodeling of arteries in response to altered loads is an area of intense interest to cardio-vascular clinicians and researchers. In humans, changes due to cardiovascular diseases (e.g. aortic dilatation) may occur slowly over many years, and mathematical models that describe the remodeling response are needed for predicting the course, and possible treatment, of these diseases. Recently, Humphrey and co-workers have proposed constrained mixture models [1] that consider local stresses in the arterial wall to be the sum of contributions from collagen, elastic fibers, and vascular smooth muscle cells (VSMCs). While numerous studies (e.g., [2]) have considered the active response of VSMCs in large arteries under quasi-static conditions, little is known about the mechanical response of VSMCs to continuous cyclic stretch. We have chosen 3-D bio-artificial tissue constructs as a model system in which to study the response of VSMCs to continuous cyclic stretch. However, VSMCs undergo a shift from a contractile phenotype to a de-differentiated phenotype during culture [3]. Some investigators have suggested that serum deprivation can induce re-differentiation toward a more contractile phenotype [4, 5]. The goal of our study was to compare the effect of incubation conditions on the active responses of VSMCs in 3-D tissue constructs to continuous cyclic stretch.
Hemodynamics in Human Abdominal Aortic Aneurysms During Rest and Simulated Exercise
Authors: Les Andrea S. , Cheng Christopher P. , Draney Blomme Mary T. , Figueroa C. Alberto , LaDisa John F. , Park Jinha M. , Herfkens Robert J. , Dalman Ronald L. , Taylor Charles A.
Published: March 2014

Abdominal Aortic Aneurysms (AAAs) — the localized enlargement of the abdominal aorta — represent the 13th leading cause of death in the United States. The natural progression of small (3–5 cm) AAAs is 2–6% growth per year until rupture or surgical repair [1]. As AAAs enlarge, adverse hemodynamic conditions (including regions of low mean wall shear stress and high particle residence time) are exacerbated under normal resting conditions.
Influence of Interleukin Treatment on Engineered and Native Articular Cartilage
Authors: Lima Eric G. , Bian Liming , Gonzales Francis B. , Ateshian Gerard A. , Hung Clark T.
Published: March 2014

Injury to the diarthrodial joint is often associated with elevated levels of cytokines and other inflammatory molecules. While the influence of interleukin on articular cartilage has been well-studied, its effects on engineered cartilage are not. The presence of inflammatory factors in the injured joint would be expected to affect the performance of implanted engineered cartilage repair tissue [1] and this effect may be especially pronounced in underdeveloped tissues [2]. The current study addresses this issue by examining the influence of interleukin (IL-1α and IL-1β) on engineered cartilage mechanical and biochemical properties at sequential stages of development. Furthermore, dexamethasone, an anti-inflammatory steroid that has been shown in some cases to suppress interleukin-induced degradation of native cartilage [3], was examined in the context of engineered constructs.
Comparison of Thermal and Non-Thermal Ablation of Tumor Using Focused Short Pulse Laser Beam
Authors: Dutta Ashim , Kramer Megan , Fahey Molly , Mitra Kunal , Grace Michael S.
Published: March 2014

For last few decades laser-induced tumor ablation has attracted significant attention of researchers. The accessibility of tumors located deep inside the body organ using fiber-optic probe without any major surgical resection has made this method an alternative for conventional surgical resection. Various minimally invasive techniques have been developed are used to ablate the tumor successfully with minimum collateral damages [1, 2]. All these techniques utilize the photo-thermal mechanism where conversion of laser energy (mainly from CW or long pulsed laser source) to heat energy leads to necrosis of the tissue through photocoagulation. Since, the necrosis of tumor is achieved by volumetric heating of the whole tumor there remains a significant chance of heat spreading out of the tumor volume damaging surrounding healthy tissue. Therefore, precise control of treatment parameters (laser pulse width, laser power, and irradiation time) is required to restrict the heat spread to the healthy tissue surrounding the tumor.
Improved Prediction of Local Trabecular Strain Enhances Non-Invasive Assessment of Micro Bone Strength Using a Surface Smoothing Technique in FEA
Authors: Ferreri Suzanne L. , Qin Yi-Xian
Published: March 2014

One key issue in clinical, non-invasive assessment of bone quality and fracture risk is the accurate prediction of localized trabecular strength through the determination of peak stress values and locations. Additionally, it has been suggested that peak stress/strain concentrations may play an important role in driving the bone remodeling process. Micro-CT based voxel finite element (FE) meshes have been widely used in nondestructive evaluation of global stiffness. Subsequently, this technique has been advantageous in studies addressing changes in bone volume and microstructure.
Screw/Plate Stability in Universal Locking Plate: A Novel Internal Fixator
Authors: Dharia Mehul A. , Forstein Micah A. , Compton Rick C. , Levine Danny L.
Published: March 2014

The recent trend in internal fixation of fractures puts a greater emphasis on biological fixation, which involves the use of locking plates and screws [1]. While conventional plates rely on frictional forces between the plate and the bone, locking plates utilize a threaded connection between screw and plate for fixation and stability [2]. Surgeons choose either type of fixation device in treatments for specific fractures and injuries.
Microindentation Testing of Rat Brain Tissue Slices
Authors: Wu James S. , Dunn Alison C. , Lee Sung J. , Sawyer W. Gregory , Sarntinoranont Malisa
Published: March 2014

In addition to traditional testing methods, which generally involve complex sample preparation, indentation exists as an alternative, non-destructive testing technique for measuring the mechanical properties of materials. Indentation is increasingly being used in the mechanical assessment of soft hydrated materials, e.g., biological tissues, because of its non-destructive nature, small sample capacity, and ability to hone in on localized regions of interest.
Effects of Tissue Swelling on Macromolecular Transport in Nervous Tissue: A Simulation Analysis
Authors: Chen Xiaoming , Sarntinoranont Malisa
Published: March 2014

Convection-enhanced delivery (CED) is a promising drug delivery method for treating diseases of the brain and spinal cord. CED infuses therapeutic agents via a cannula directly into the intraparenchymal space, circumventing the blood–brain barrier (BBB) and improving drug targeting [1]. CED enhances the transport of macromolecules by introducing convective transport to supplement diffusive transport.
Treatment of Cerebral Aneurysms With Flow Divertors: Long Term Results in an In Vivo Model
Authors: Sadasivan Chander , Lieber Baruch B. , Cesar Liliana , Seong Jaehoon , Wakhloo Ajay K.
Published: March 2014

Subarachnoid hemorrhagic stroke is a devastating illness with a 30-day mortality rate of 45% and is mostly caused due to the rupture of an intracranial aneurysm. Although these aneurysms are currently treated surgically by clipping, or, endovascularly by coiling and stent-assisted coiling, the feasibility of successfully treating aneurysms solely by the placement of an intravascular flow-diverting mesh across the aneurysm neck was established more than a decade ago [1]. Flow divertors disrupt the momentum exchange between the parent artery and aneurysm and significantly reduce intraaneurysmal hydrodynamic vorticity. The resultant flow stasis promotes thrombus formation within the aneurysm sac, which eventually matures into fibrotic tissue, leading to the exclusion of the aneurysm from the circulation. With the increased use of stents in the intracranial circulation, cases where coiling is not feasible, or is staged as a secondary procedure, are providing clinical evidence of the successful treatment of aneurysms with stents alone [2,3]. Such reports are sporadic and, moreover, the devices used are not designed to be flow divertors. Methodological evidence of the performance of appropriately designed flow divertors in treating cerebral aneurysms is currently unavailable.
Plaque and Shear Stress Distribution in Human Coronary Bifurcations: a Multi-Slice Computed Tomography Study
Authors: van der Giessen Alina G. , Wentzel Jolanda J. , van de Vosse Frans N. , van der Steen Antonius F. , de Feyter Pim J. , Gijsen Frank J.
Published: March 2014

It is generally accepted that early atherosclerosis develops in low shear-stress (SS) regions such as the outer wall of arterial bifurcations and the inner bend of curved vessels (1). However, in clinical practice, it is common to observe atherosclerotic plaques at the flow-divider, or carina, of coronary bifurcations (2). Plaques at the carina are more frequently found in symptomatic patients, and may represent a more advanced stage of atherosclerosis. The carina is located in a region which is exposed to high SS. We hypothesize that if plaques are located in atheroprotective high SS regions, they have grown circumferentially from the atherogenic low SS regions.
Simulation of Blood Perfusion in Tumour Microvasculature
Authors: Wu Jie , Xu Shixiong , Long Quan , Collins Michael W. , Koenig Carola S. , Zhao Gaiping , Jiang Yuping , Padhani Anwar R.
Published: March 2014

Solid tumor has become one of the most serious diseases that threaten mankind’s health and life all over the world. It is well recognized that structural and functional abnormalities of tumor vascularity and the subsequent microenvironment and cellular adaptive consequences creates a great barrier for drug delivery in solid tumors, contributing to treatment resistance. Hence, the investigation of microcirculatory dynamics in solid tumors has important significance for improving the effectiveness of many anticancer therapies.
Culture Medium With Blood Analog Mechanical Properties
Authors: van den Broek Chantal N. , Rutten Marcel C. M. , Frøbert Ole , van de Vosse Frans N.
Published: March 2014

Culture of arteries has become increasingly important in studying atherosclerosis and the effect of clinical interventions [1]. Ideally, arterial culturing should imitate in vivo conditions within an ex vivo environment. Physiological wall shear stresses are important as they induce an atheroprotective endothelial phenotype [2], which is relevant for maintaining arterial wall integrity. The arteries in such ex vivo studies, however, are perfused with culture medium, which has a viscosity lower than blood. Previously, the culture medium has been supplemented with dextran to obtain physiological fluid viscosity and wall shear stresses. However, several researchers [3,4] reported side effects of dextran on the cells in the arterial wall independent of its effect on medium viscosity. Also, dextran increases medium osmolality to supraphysiological levels [5]. This suggests that dextran may not be the optimal substance to increase medium viscosity.
Characterizing Strain in the Tibia of Rats Exposed to Hindlimb Unloading With an Exercise Countermeasure
Authors: Jeffery J. M. , Murphey M. C. , Stallone J. L. , Bloomfield S. A. , Hogan H. A.
Published: March 2014

The purpose of this research was to characterize the strains in the rat tibia induced by controlled muscle contractions of the lower limb. The muscle contractions were generated unilaterally by electrical stimulation of the sciatic nerve in anesthetized animals. The technique was developed by muscle biologists as a way of simulating resistive exercise, and it was used in the current research as a countermeasure for rats undergoing hindlimb unloading to simulate musculoskeletal effects of space flight. The intensity of muscle contraction is quantified by measuring the torque generated at the ankle joint. A wide range of torques can be generated by varying the frequency of the electrical stimulating signal. Three specific questions were addressed in the current study. First, what is the relationship between strain and torque? Second, does the relationship between strain and torque change during the period of hindlimb unloading with exercise? Third, are the strain magnitudes in the range generally regarded to be osteogenic? This project is part of a larger effort aimed at assessing the efficacy of the muscle stimulation method as a countermeasure for the negative musculoskeletal effects of mechanical unloading.
Validation of a High-Payload Robotic/UFS Testing System for Studying of Joint Motion
Authors: Lorang Noah H. , Hellmann Lauren A. , Wu Changfu , Woo Savio L.-Y.
Published: March 2014

Robotic technology has been adopted for studying the biomechanics of the knee joint by our research center and others since 1993 to gain a fundamental understanding of the knee, as well as to provide orthopedic surgeons with scientific data on the efficacy of various reconstructive techniques [1–4]. A robotic testing system generally consists of a six degree-of-freedom (DOF) robotic manipulator with a universal force-moment sensor (UFS) attached to the end effector [5]. This testing system offers a wide range of motion with precision path and position repeatability.
Rotational Acceleration Duration Affects Brain Strains in Lateral Impact
Authors: Li Jianrong , Zhang Jiangyue , Yoganandan Narayan , Pintar Frank A. , Gennarelli Thomas A.
Published: March 2014

Traumatic brain injury is a leading cause of disability and fatality in the United States. Approximately two million traumatic brain injury cases occur every year [1]. Motor vehicle crashes are a primary source [2]. Both clinical and laboratory studies have been conducted to understand injury mechanisms and establish injury thresholds [3, 4]. Physical models have also been used to investigate injury biomechanics [5, 6]. Angular acceleration is considered as a major cause of diffuse brain injuries (DBI) [7, 8], while the angular velocity is chosen as a suitable load descriptor for a diffuse brain injury criterion [4]. The present study is focused on the effect of angular acceleration duration on brain strains due to lateral impact.
Effect of the Red Blood Cells on the Primary Thrombus Formation
Authors: Yano Koichiro , Mori Daisuke , Tsubota Ken-ichi , Ishikawa Takuji , Wada Shigeo , Yamaguchi Takami
Published: March 2014

It has been pointed out that some mechanical factors play important roles in a series of physiological or biochemical processes during the thrombus formation. Recently, many studies including the authors’ work qualitatively demonstrated how the thrombus is regulated under the influences of the blood flow and the intercellular molecular bridge using computational fluid dynamics techniques[1–4]. They verified the importance of the balance of them in the process of the thrombus formation. However, few studies have taken into account the existence of the other cell constituents than the platelet such as red blood cell (RBC).
Numerical Simulation of Blood Flow Through Mechanical Heart Valves Using Meshless Techniques
Authors: Roldán Alejandro , Sweitzer Nancy , Osswald Tim , Chesler Naomi
Published: March 2014

Heart valve disease is a major contributor to cardiovascular mortality and morbidity. While bioprosthetic valves have satisfactory hemodynamic performance, mechanical heart valves (MHVs) are more durable, so their clinical use is increasing [1]. Unfortunately, current MHVs cause flow abnormalities, thrombosis and hemolysis [2]; they are therefore at a stage far from duplicating the function of natural valves. Recent improvements in computer performance and numerical methods have resulted in significant breakthroughs in MHV design [2]. In particular, computational fluid dynamics has been used to redesign valves to minimize the production of turbulence, regions of high shear stresses, pressure loss and stagnation regions in the vicinity of the leaflets [3]. These studies have, for the most part, used numerical techniques that require domain discretization such as finite element methods (FEM) or finite difference methods (FDM). However, these methods cannot represent the complexity of the moving and deforming boundaries present in an operating valve without extraordinarily high computational costs. That is, methods that use domain discretization require a fine mesh in small gaps between leaflets and near the valve housing. As a result, simplifying assumptions are typically made which introduce error into the results. We have recently implemented two meshless numerical techniques — the boundary element method (BEM) and the radial functions method (RFM) — that compute fluid flow fields without domain discretization and thus can model valve leaflet motions and unsteady flow with reasonable computational costs. The goal of this study was to model blood flow through mechanical heart valves using these techniques. In this paper we present the results of BEM simulations of heart valves in a range of open states. RFM techniques, which can efficiently simulate the nonlinear effects of inertia in the domain, are also described.
Hepatic Venous Blood Flow Distribution in the Total Cavopulmonary Connection: Patient-Specific Anatomical Models
Authors: Dasi Lakshmi , Pekkan Kerem , Whitehead Kevin , Fogel Mark , Yoganathan Ajit
Published: March 2014

CFD modeling of the anatomical pathways (TCPC) created by the palliative single-ventricle heart defect surgeries is an area studied by several research groups [1–5]. To the best of our knowledge except Walker et al. (in idealized experimental models) [6], all studies focused on the prediction of hydrodynamic power losses or dissipation function and ignored venous hepatic flow distribution to the left and right lungs. Hepatic flow coming from the inferior vena cava (IVC) transports essential growth factors that are required for normal lung growth. Inadequate IVC blood distribution also cause protein loosing enteropathy [7], a serious complex pathology leading to total failure of the surgically created single-ventricle circulation system. Early TCPC configurations distributing the hepatic flow unidirectionaly to one of the lungs [8] were promptly discontinued from the operating rooms and replaced with “+” shaped connections for these reasons, Fig 1.
Arterial Flows in Carotid Artery Dissection
Authors: Jou Liang-Der , Lee Deok Hee , Mawad Michel E.
Published: March 2014

Dissection at the carotid artery is not infrequent, and it may lead to arterial stenosis, dissecting-aneurysm, ischemia stoke, or subarachnoid hemorrhage [2]. The exact cause of carotid artery dissection remains unknown, but it occurs often among young and middle-aged individuals who are otherwise healthy [3]. Extra-cranial carotid dissection is often managed conservatively by anti-thrombotic therapy, while the intracranial carotid dissection often requires interventional management.
Influence of Walking Speed and Severity of Knee Osteoarthritis on Medial Compartment Loading
Authors: Zeni Joseph , Higginson Jill
Published: March 2014

Progression of knee osteoarthritis (OA) has been shown to occur in the presence of an increased load at the medial compartment [1]. Current gait analysis techniques allow researchers to use inverse dynamic techniques to calculate external knee adduction moments. These moments correlate to varus knee stresses and increased load in the medial knee compartment. These abnormal stresses have been hypothesized to play a role in the destruction of articular cartilage [2]. Previous authors have suggested that walking velocity will affect the adduction moment and that decreasing walking speed may reduce the maximal knee external moment during gait [3]. Based on these previous findings, we investigated various walking speeds in subjects with mild, moderate and severe OA and the effect on the external knee adduction moment.
Changes in Material Properties of Dialysis Membranes Due to the Effect of High Flux Dialysis
Authors: Aksoy Emin M. , Usta Metin , Ucisik Ahmet H.
Published: March 2014

Due to their clinical outcome high flux dialysers containing new generation of dialyser materials have been widely used for patients with chronic renal failure within the last decade [1]. Dialyser membranes are more prone to damage to to the harsh environment during high flux dialysis. Reuse of dialysers has advantages like better biocompatibility and lower cost, any damage of the dialysers membrane during reuse of the dialysers can also cause very serious clinical complications. Therefore reuse of the dialysers is an issue that has to be approached more cautiously. In this study polysulphone dialyser membranes were being investigated in terms of mechanical properties and changes in crystallinity before and after dialysis sessions. Dialysis sessions were performed on five patients with dialysis age less than two years and without any other accompanying disease at the Hemodialysis Department of Istanbul Haydarpasa Numune State Hospital.
Fluid Dynamic Events Within the Vitreous Cavity Induced by Saccadic Eye Rotations
Authors: Cafferata Chiara , Repetto Rodolfo , Siggers Jennifer , Stocchino Alessandro
Published: March 2014

The vitreous cavity constitutes most of the eye volume and is filled by the vitreous humour or vitreous body. It has the shape of a weakly deformed sphere, the deformation being essentially due to the presence of the lens, which produces an inward indentation in the anterior part of the chamber. Under normal conditions the vitreous body has the consistency of a gel with viscoelastic rheological behaviour [1]. Ageing gradually disintegrates the gel structure leading to a partial or total vitreous liquefaction. After some surgical procedures (vitrectomy) the vitreous body may be completely replaced by “tamponade fluids”, typically silicon oils, which are left for a certain time within the eye and are eventually replaced by water.
Biaxial Testing of Human Pericardium: A Comparative Study of Fixed and Fresh Tissue
Authors: Zigras Tiffany C. , Nagano Naoko , Tremblay Dominique , Rouleau Leonie , Mongrain Rosaire , Cartier Raymond , Leask Richard L.
Published: March 2014

The objective of this study is to examine the differences in biomechanical properties of fresh and glutaraldehyde fixed pericardium tissue to better utilize this tissue in cardiovascular surgery.
Three Dimensional Numerical Analysis of Flow Through the Human Carotid Bifurcation With Varying Degrees of Stenotic Plaque Formation
Authors: Lovald Scott T. , Khraishi Tariq , Heinrich Juan C. , Yonas Howard , Taylor Christopher L.
Published: March 2014

The human carotid artery bifurcation is often affected by plaque and atherosclerotic formations. A high degree of stenosis due to plaque deposit in the carotid artery can significantly diminish blood flow to the brain [1]. For three decades, local flow anomalies such as flow separation, recirculation, low wall shear stress, and high local particle residence time are factors that have been implicated in the development of arterial diseases [3, 1]. Numerical analysis of flow through a stenotic carotid bifurcation provides insight into local flow dynamics and an assessment of the risks of particular modes and degrees of stenosis.
Resultant Carpal Kinematics With Respect to Muscle Force Application
Authors: Patterson Rita M. , Buford William L. , Andersen Clark L. , Viegas Steven F.
Published: March 2014

Purpose: The purpose of this study was to investigate the kinematics of seven carpal bones during a simulated active (tendon-driven) and passive (externally-assisted) motion of the wrist.
Superelasticity of Vimentin Coiled-Coil Intermediate Filaments: Atomistic and Continuum Studies
Authors: Ackbarow Theodor , Buehler Markus J.
Published: March 2014

Vimentin coiled-coil alpha-helical dimers are elementary protein building blocks of intermediate filaments (IFs), an important component of the cell’s cytoskeleton that has been shown to control the large-deformation behavior of eukaryotic cell [1].
Micro CT-Based Large Scale Finite Element Modeling of Compressive and Torsional Properties of Human Cortical Bone
Authors: Yeni Yener N. , Zauel Roger R.
Published: March 2014

Cortical bone tissue quality is imperative in maintaining the mechanical competence of whole bones, particularly at sites of overuse and age-related fragility fractures where a considerable cortical bone component is present. (Note that cortical bone tissue is more than 80% of the bone in the body [1].)
Towards a Unified Multi-Scaled Theoretical-Experimental Paradigm for Characterizing Vascular Remodeling
Authors: Gleason Rudolph L.
Published: March 2014

Vascular remodeling plays a key role in many physiological and pathophysiological processes, as well as the success or failure of many clinical interventions; examples include vascular development and aging, hypertension and atherosclerosis, and restenosis of vascular grafts. Despite the explosion of information on vascular remodeling, from the molecular level to the tissue level, attempts at integrating these data into a predictive multi-scale model are still in their infancy. Humphrey and Rajagopal said well that in order to capture the salient features of these remodeling processes ‘one must track local balances or imbalances in the continual production, removal, [and remodeling] of individual constituents, the mechanical state in which the constituents are formed, and how these constituents are organized’. Abdominal aortic aneurysms (AAA’s) provide a good illustration of the need for a multi-scaled microstructurally-motivated mathematical model. During progression of AAA’s, circumferential expansion, vessel wall thinning and axial lengthening are coincident with a progressive loss of elastin and smooth muscle and decrease in glycosaminoglycans, with mature aneurysms consisting primarily of collagen and fibroblasts; thus, AAA’s experience spatial and temporal variations in their geometry, microstructural content and organization, and applied loads. To develop a predictive model for vascular remodeling, the complex interplay between evolving material behavior (via changes in microstructural content and organization) and applied loads, which determine the local mechanical environment and the mechano-biological response to this changing mechanical environment, must be incorporated.
Patient-Specific Fluid Structure Interaction Simulation Applied to Evaluating Hemodynamics Within the Total Cavopulmonary Connection
Authors: Wang Rui , Lacour-Gayet Francois G. , Lanning Craig , Hunter Kendall , Shandas Robin
Published: March 2014

Congenital heart disease (CHD), a life-threatening birth disorder, is the most common genetic disorder with an incidence rate as high as 1% in neonates (36,000 cases in 2006). Amongst these children, one out of four has single ventricle anomaly. As a palliative rather than a curative means for vascular reconstruction, the “Fontan” palliation has been used to produce stable hemodynamic states, at least for a limited period of time. However, the majority of post-Fontan patients faces a high risk of mortality and morbidity [1], and will have to undergo heart transplant eventually due to the excess load imposed on the single ventricle by the systemic resistance.
Multi-Scale Models of Epithelial Cell Injury and Detachment During Microbubble Flows
Authors: Dailey Hannah L. , Yalcin Huseyin C. , Ghadiali Samir N.
Published: March 2014

Certain pathological conditions, e.g. pneumonia or acute lung injury, can lead to fluid buildup in the small pulmonary airways. During breathing, micron-sized air bubbles propagate through the fluid-occluded airways and these microbubbles may exert injurious hydrodynamic stresses on the epithelial cells (EC) which line airway walls. Specifically, the pressure and shear stresses generated during microbubble flows may cause plasma membrane rupture [1], cell detachment [2] and an exacerbation of the existing lung injury.
Optimization of Quadriceps Force Distribution for Minimization of Patellofemoral Contact Pressure During a Squat
Authors: Shankar Aarthi S. , Guess Trent M.
Published: March 2014

Patellofemoral Pain (PFP) syndrome is a very common knee disorder. A possible cause may be excessive lateral force applied by the quadriceps and the patellar tendon producing an abnormal distribution of force and pressure within the patellofemoral joint [1]. EMG and in-vivo studies have been conducted to understand the function of the quadriceps and its relationship with PFP [2,3]. These studies suggest a strong relationship between muscle forces and PFP which originates from high lateral retropatellar contact forces. A dynamic computational model of the knee was developed which includes the quadriceps muscles Rectus Femoris (RF), Vastus Intermedius (VI), Vastus Lateralis (VL), and Vastus Medialis (VM) represented as force vectors. The model can predict retro-patellar contact pressures and the action of the individual quadriceps muscles based on the predicted pressures. The objective of this study was to develop a control system which could optimize the distribution of quadriceps muscle forces to minimize contact pressure between the patella and the femur of the knee during a squat.
Effects of Anomalous Diffusion Mechanisms in Developing Tissue Engineered Constructs
Authors: Chao Gabriel , Oomens Cees , van Donkelaar Rene , Baaijens Frank
Published: March 2014

Many diffusive processes in biological systems refuse to obey the standard laws of diffusion. In normal diffusion, the diffusivity can be considered constant and the concentration of the diffusive particles follows Fick’s law. However, in highly heterogeneous materials such as tissues, the complex microgeometry of the medium imposes serious restrictions to the mobility of the particles. This scenario is known as anomalous diffusion. Experiments in diverse biological systems including diffusion in the extracellular space of the brain [1], morphogen movement in the extracellular environment [2], protein movement inside cells [3], identified anomalous, rather than Fickian, transport.
Multiphasic Mechano-Electrochemical Finite Element Model of Human Intervertebral Disc
Authors: Yao Hai , Gu Wei Yong
Published: March 2014

The intervertebral disc (IVD) is the largest cartilaginous structure in human body that contributes to flexibility and load support in the spine. To accomplish these functions, the disc has a unique architecture consisting of a centrally-located nucleus pulposus (NP) surrounded superiorly and inferiorly by cartilage endplates and peripherally by the annulus fibrosus (AF). Because the disc is avascular and experiences mechanical loads, the cells in IVD tissues live in a complex physical environment. Knowledge of mechanical, chemical and electrical signals within the tissue is important for understanding mechanobiology of IVD [1]. The objective of this study was to develop a three-dimensional (3D), inhomogeneous finite element model (FEM) for human IVD for analyzing the physical environment and solute transport within the tissue under different mechanical loading conditions. A case of IVD under axial compression was simulated and reported.
Quantifying Variations in Collagen Matrix Deformation in Loaded Articular Cartilage
Authors: Briant Paul , Bevill Scott , Andriacchi Thomas P.
Published: March 2014

Mechanical loads have been shown in numerous studies to affect the health of articular cartilage [1]. Regional variations in the local deformation within articular cartilage under both normal and abnormal loading are, however, poorly understood. Understanding these deformation patterns is important, since conditions such as anterior cruciate ligament injury have been suggested to initiate cartilage breakdown by shifting the regions of frequent loading within the joint [2]. Quantifying variations in the deformation behavior of the collagen matrix in cartilage under load will therefore provide insight into the mechanical environment within cartilage and test the feasibility of a kinematic pathway to the initiation of osteoarthritis (OA). The objective of this study was to test the hypothesis that the collagen matrix in two regions of cartilage that normally experience different applied loads will deform differently under the same applied load.
A Rat Model of Osteoarthritic Temporomandibular Joint Pain: Mechanically-Induced Behavioral Hypersensitivity and Histologic Modifications
Authors: Nicoll Steven B. , Hee Christopher K. , Davis Martin B. , Winkelstein Beth A.
Published: March 2014

Orofacial pain associated with osteoarthritis (OA) in the temporomandibular joint (TMJ) is a significant clinical problem [1]. The pathophysiologic and cellular mediators that underlie the development of such chronic orofacial pain are not well understood, nor has a relationship to mechanical loading been defined. Several experimental models have been developed to examine causative factors in TMJ OA progression and joint pathology. Such models often involve intra-articular injections or surgical manipulation of tissue structures in order to alter joint kinematics and stability [2–6]. For example, severing of the discal attachments followed by anterior displacement of the disc has been employed in a rabbit model, while disc perforation and scraping of the condylar surface have been used in sheep models to induce OA symptoms [2,3]. A limitation of the above approaches is that they introduce artificial damage to the joint structures and do not approximate the clinical disorder of mechanically-induced TMJ OA. Therefore, the goal of this pilot study was to develop a novel model of TMJ OA via non-invasive and mechanically relevant methods that could produce behavioral hypersensitivity (mechanical allodynia) suggestive of pain symptoms and histological changes in the TMJ consistent with osteoarthritic pathology.
Thermoregulation in Humans: Results From an Anatomically-Based, High-Resolution Voxelized Model
Authors: Nelson David A. , Curran Allen R. , Marttila Eric A. , Charbonnel Sylvain , Fiala Dusan
Published: March 2014

The ability to predict local surface and internal temperatures in humans subjected to various environmental and direct thermal loads has applications which include assessment of human exposure to radio frequency radiation (RFR) from mobile phones [1], medical imaging technologies [2] and mild-temperature hyperthermia (MTH) treatment for some cancers [3].
Collocation of Macrophages and Mechanical Stress in Human Coronary Atherosclerotic Plaque
Authors: Hallow K. Melissa , Carnell Peter C. , Taylor W. Robert , Vito Raymond P.
Published: March 2014

Cardiovascular disease (CVD) is the leading cause of death in the United States. One of the primary causes of CVD is atherosclerosis, a progressive disease that begins with the deposition of lipid on arterial walls to form plaque. Over time, some plaques progress to an unstable configuration that is vulnerable to rupture, while others remodel to more stable configurations. The factors directing plaque progression toward instability are poorly understood.
Effects of Discontinuous Fiber Reinforcement on the Mechanical and Thermomechanical Properties of a Shape Memory Polymer
Authors: Lyons Michael B. , Shandas Robin
Published: March 2014

Over the last few years, we have developed shape memory polymers (SMPs) with several properties suitable for use in minimally-invasive biomedical devices. These properties include biocompatibility, the ability to fully recover large strains, the potential to serve as medication reservoirs for drug delivery, and low production cost. We and others have proposed use of shape memory polymers for various applications including cardiovascular stents, an endovascular clot removal system, and a self-tying suture.
Ameliorating Glycosaminoglycan (GAG) Loss and Cell Death in Articular Cartilage Following Single-Impact Loading
Authors: Natoli Roman M. , Athanasiou Kyriacos A.
Published: March 2014

Impact loading of articular cartilage leads to post-traumatic osteoarthritis (OA) through its effects on the cells and extracellular matrix (ECM) of the tissue. Studies have shown the level of impact or injurious compression correlates with increased cell death, degradation of the ECM, and detrimental changes in biomechanical properties [1]. Recently, several bioactive agents, such as P188 and IGF-I, have shown promising results by reducing cell death following injurious compression of cartilage explants [2, 3].
Scaffold Properties Play a Critical Role in the Retention of Synthesized Glycosaminoglycans in Tissue Engineered Cartilage
Authors: Kugler Lindsay E. , Ng Kenneth W. , O’Conor Christopher J. , Ateshian Gerard A. , Hung Clark T.
Published: March 2014

Agarose has been used as a model scaffold for cartilage tissue engineering research due to its maintenance of chondrocyte phenotype, support of cartilage tissue development, and ability to transmit mechanical stimuli [1–4]. In a previous study, the temporal application of TGF-β3 for only 2 weeks resulted in explosive growth in the functional properties of tissue engineered cartilage [5]. The role of scaffolds in tissue engineering includes providing a physiologic three-dimensional environment for cells, decreased path lengths for diffusion and retention of cell elaborated matrix. In past studies by our laboratory, it was hypothesized that the scaffold properties in engineered cartilage plays a crucial role in the retention of synthesized glycosaminoglycan (GAG) molecules, a major extracellular matrix constituent of articular cartilage [6, 7]. This study focuses on testing this hypothesis using 3%, 2%, and 1% (wt/vol) agarose as scaffolds for engineered cartilage.
MMP-2 and -9 Collocate With High Stresses Predicted Using Heterogeneous Mechanical Model of Arteries
Authors: Kim Yu Shin , Galis Zorina S. , Rachev Alexander , Vito Raymond P.
Published: March 2014

Mechanical stimuli influence vascular cell functions related to remodeling. The effect of mechanical environment on cell functions has been studied at tissue and cell levels. Tissue level studies provide the distribution of biological responses of cells in their natural environment. Cell culture studies provide better control of mechanical stimuli applied to cells in an artificial environment. Since mechanical stress and strain cannot be measured in situ, mathematical models are necessary to interpret results from tissue level studies using relationships established in cell culture studies.
An Implantable Transit-Time Aortic Flow Probe Using Capacitive Micromachined Ultrasound Transducers: Design and Optimization
Authors: Liu Jessica , Shandas Robin
Published: March 2014

Monitoring cardiac output continuously post-surgery for children with congenital heart disease is an important part of post-operative recovery, especially given the potential for large changes in vascular pressure as a side-effect of pharmaceutical agents given to help recovery. Current methods to monitor cardiac output are limited by the requirement for invasiveness (cuff-type flow probes), or do not provide continuous monitoring (ultrasound Doppler). Using a combination of analytical and finite element modeling, we explore the design and optimization of a unique ultrasonic transit-time flow probe that extends the capability of current devices by providing greater miniaturization, better sensitivity, and lower cost through the use of capacitive micromachined ultrasound transducer (cMUT) technology.
Dynamic Imaging of the Lumbar Spine
Authors: Pfeiffer Ferris M. , Ward Carol V. , Abernathie Dennis L.
Published: March 2014

Low back pain afflicts roughly two thirds of all adults at some time, making it second only to upper respiratory problems as the leading health care complaint in America [1]. Often low back pain goes undiagnosed. Association of symptoms with imaging results is weak [2]. Thus, “If...an anatomical diagnosis for low back conditions is impossible 80%–90% of the time, being able to differentiate normal spinal function from what is abnormal may be fundamental in creating a diagnosis based on spinal function rather than aberrant anatomy” (page 57) [3].
A Three Dimensional Simulation of Fluid-Structure Interaction
Authors: Liu Kunlun , Barocas Victor H.
Published: March 2014

A numerical method is presented for calculating 3-D unsteady flow through bileaflet heart valves and flexible obstruction. The method combines finite volume, finite element, and overlapping grid methods. The employed overlapping grid method decomposed the entire domain into the solid region, the fluid region in the vicinity of the solid (the inner region), and the outer fluid region. A finite volume scheme was implemented for the outer fluid region, while a finite element scheme was employed in the solid and inner fluid regions. Calculations were carried out for the full 3-D valve geometry under steady inflow conditions with the Reynolds number ranging from 400 to 1200.

The numerical results illustrate the evolution of the downstream vortices. The changes in the location and size of the reattachment vortices in response to the change of elastic modulus of solid and Reynolds number of fluids were recorded and tabulated. The results provide the detailed information sketching the evolution of the fluid-structure interaction in terms of the modes and amplitude.
Cells on a Bed of Micro-Needles: Modeling of the Scaling of the Response
Authors: McGarry J. P. , Chen C. S. , Deshpande V. S. , McMeeking R. M. , Evans A. G.
Published: March 2014

The behavior of a cell attached to a bed of micro-needles is investigated using a bio-chemo-mechanical model. In experiments, the cell is spread on the tips of the micro-needles to which it is attached by focal adhesions bonded to ligands in the fibronectin on the posts. Actin stress-fibers form and attach to the focal adhesion plaques and exert contractile force on the micro-needles. As a result, the posts deflect and their displacements are measured and used to calculate the applied forces. This step is straightforward, because the cells do not adhere to the flanks of the micro-needles, and Euler-Bernoulli beam theory can be used to convert the bending displacements to applied loads. The bio-chemo-mechanical model for the cytoskeleton incorporates a signal, the tension-stabilized formation of actomyosin stress fibers, and their myosin motor driven contractility. In conjunction, the focal adhesions are modeled to account for their mechanosensitivity, in which loads transmitted to them from the stress-fibers encourage the development of plaques attached to the fibronectin on the micro-needle tips. These features have been programmed into a finite element code (ABAQUS) and used to simulate the behavior of cells attached to a bed of micro-posts. The micro-needles themselves are modeled as elastic structures and, consequently, the contractile force applied by the cells causes them to bend. The model of a cell on micro-needles successfully reproduces the characteristics of the data from the experiments. The scaling of the behavior in terms of micro-needle height, diameter, spacing, and elastic stiffness is investigated. In addition, the parameters of the bio-chemo-mechanical model of the cytoskeleton and the focal adhesions are varied (contractile tension, rate of stress-fiber contraction, persistence time for the signal and the effective stiffness of the focal adhesions) and their effect on scaling of the response also investigated. The results provide insight into the bio-chemo-mechanical response of cells to biological stimuli. The scaling simulations also give guidance on how experiments utilizing cells on micro-needles can be designed to extend the understanding of the mechanosensitivity of cells.
Consequences of Long-Term Cyclic Indentation on Initially Intact Cartilage
Authors: Wu Bruce Y. C. , Gray Martha L. , Socrate Simona
Published: March 2014

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