bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-Destructive and Non-Invasive Assessment of Mechanical Properties in Heart Valve Tissue Engineering
Authors: Kortsmit Jeroen , Driessen Niels J. B. , Rutten Marcel C. M. , Baaijens Frank P. T.
Published: March 2014

Despite recent progress, mechanical properties of tissue engineered heart valves still lack mechanical strength compared to native aortic valves [1]. Although cyclic tissue straining in bioreactor systems is known to enhance tissue formation [2], specific optimal loading protocols have not yet been defined. To get a better insight in the effects of mechanical loading on tissue development, mechanical behavior of tissue constructs should be monitored and controlled during culture. However, currently used methods for mechanical characterization (e.g. tensile tests, indentation tests) are destructive and can therefore only be performed at the end stage of tissue culture. An experimental-numerical approach was previously proposed by which leaflet deformation was assessed during culture in a bioreactor system, real-time and non-invasively [3]. Further development of this approach now enables a non-invasive and non-destructive assessment of mechanical properties of engineered heart valve leaflets.
The Effect of Parkinson’s Disease on the Step Response to a Backwards Pull
Authors: McVey Molly A. , Stylianou Antonis P. , Luchies Carl W. , Lyons Kelly E. , Pahwa Rajesh , Jernigan Stephen , Mahnken Jonathan
Published: March 2014

Postural instability is one of the most disabling symptoms of Parkinson’s disease (PD) and often leads to falls. Falls can have severe physical, psychological, and economic impacts including fractures, fear of falling, and loss of independence [1]. Effective interventions to reduce fall risk exist [2, 3] and would be most effective if they could be implemented prior to a fall occurring. Unfortunately, the current methods to evaluate postural instability in PD are not sensitive enough to predict those who are at an increased risk of falling so it is difficult to identify the best time to begin fall interventions.
High Frequency Precise Ultrasound Imaging System to Assess Mouse Hearts and Blood Vessels
Authors: Mahmoud Ahmed M. , Cortes Daniel H. , Mustafa S. Jamal , Mukdadi Osama M.
Published: March 2014

Genetically modified mice provide a powerful tool for understanding the molecular mechanisms and pathogenesis of human cardiovascular diseases like human atherosclerosis [1]. Numerous mouse strains are available today with phenotypes relevant to human cardiovascular diseases [1,2]. These mouse strains have prompted the development of techniques for assessing the cardiovascular function and morphology of living mice. Recently, several imaging techniques have been emerged as promising non-invasive imaging modalities, such as electron-beam computed tomography, magnetic resonance imaging, positron emission tomography, optical coherent tomography, and ultrasound biomicroscopy (UBM) [3,4]. Although these systems are capable of detecting anatomic and functional information, they may not be suitable to image mouse heart vasculatures. The small size and rapid movement of mouse hearts require systems acquiring images using temporal resolution of less than 10 ms with spatial resolution of 100 μm or less [4]. However, in mice, which have extremely small coronary arteries and high heart rates, the coronary circulation constitutes a great challenge for these available imaging techniques.
A Nonlinear Biphasic Hyperelastic Model for Acute Hydrocephalus
Authors: Smith Joshua H. , García Jose Jaime
Published: March 2014

The cerebrospinal fluid present in the central nervous system plays an important role in the physiological activities and protection of the brain. Disruptions of CSF flow lead to different forms of a disease known as hydrocephalus, characterized by a significant increment of the ventricular space. In acute hydrocephalus the Sylvius aqueduct is blocked and ventricular pressure is greatly increased.
Accuracy of Cell Mechanical Measurements Using Oscillating Optical Tweezers: A Computational Study
Authors: Ricles Laura M. , Dailey Hannah L. , Ghadiali Samir N.
Published: March 2014

The accurate characterization of living cell micro-mechanical properties is a clinically important problem since several disease pathologies depend on the deformation response of cells to applied mechanical loads. For example, the acute respiratory distress syndrome (ARDS) is characterized by an increase in the permeability of the alveolar-capillary barrier, resulting in an influx of edema fluid into the lung. Due to the surfactant inactivation and decreased gas exchange, ARDS patients must be mechanically ventilated [1,3]. However, hydrodynamic stresses exerted on the epithelial cells (EpC) that line airway walls during the reopening of the collapsed or fluid-filled airways can lead to further injury known as ventilator-induced lung injury [1].
Factors Affecting Protein Distribution and Structure in a Dried Droplet
Authors: Ragoonanan Vishard , Aksan Alptekin
Published: March 2014

Convective/diffusive drying of biopreservation solutions that contain biological macromolecules or organisms is widely-utilized, especially in desiccated and vitrified state preservation. Typically, solutions are deposited on a surface as thin films or droplets and are dried in a controlled environment. A typical biopreservation solution contains the biomaterial to be preserved, non-reducing sugars (trehalose, sucrose, etc.), polyols, and salts [1]. There are several factors that affect the overall stabilization and storage efficiency of a biopreservation solution: the properties of the chemicals in the solution, the thermodynamic state of the product to be stabilized, the processing conditions, and the interactions of the solution with the surface it is dried on. For example, during drying of a sessile droplet in a low relative humidity environment, secondary flows form within the droplet due to contact line pinning and non-uniform surface flux. These flows mainly cause accumulation of solutes at the droplet’s periphery [2]. An additional factor is the specific interactions among the constituents of the biopreservation solution, which can affect the stability of the biological material.
Elastin Haploinsufficiency Is Associated With Altered Interstitial Phenotype and Progressive Aortopathy
Authors: Gruber Matthew J. , Krishnamurthy Varun , Narmoneva D. A. , Hinton Robert B.
Published: March 2014

Supravalvular aortic stenosis (SVAS) [1] is a disease of the cardiovascular system that leads to narrowing of the large arteries in humans. Studies have shown [2] that SVAS is caused by mutations or deletions in the elastin gene resulting in elastin haploinsufficiency. Elastin haploinsufficiency results in systemic hypertension [3], thinner and more numerous elastic lamellae [4], and altered arterial mechanics [5]. Genetically modified elastin deficient mice (ELN+/-) recapitulates the human phenotype including obstructive arterial disease and decreased arterial compliance [1,3]. Elastin deficiency in these mice is associated with changes in the mechanical microenvironment in the vascular wall [6], including enhanced wall thickness, increased smooth muscle cell (SMC) proliferation [7] and stiffening of arteries [8]. However, the molecular mechanisms for these changes are not fully understood. Also from a developmental perspective, no information is available regarding initiation and progression of aortic pathology in ELN+/− mice with time. The objectives of this study were to determine the temporal effects of elastin haploinsufficiency on the functional properties of aortic tissue and the aortic cell phenotype, using the elastin deficient mouse model (ELN+/-). We hypothesized that elastin haploinsufficiency will result in progressive abnormalities in aortic stiffness and dynamic alterations in aortic smooth muscle cell phenotype.
Mechanics of Aortic Smooth Muscle Cells in Tissue Constructs: Effects of Matrix Composition
Authors: Du Wei , Pryse Kenneth M. , 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 coworkers have proposed constrained mixture models [1] that can describe these acute and chronic changes[2, 3]. These models consider local stresses in the arterial wall to be the sum of individual contributions from collagen, elastic fibers, and vascular smooth muscle cells (VSMCs) Therefore, the mechanical behavior of VSMCs (presumed to be mechanically in parallel) should be independent of the exact composition of the extracellular matrix (ECM) at any specified stage of tissue remodeling. Previously we have studied the mechanics of VSMCs in 3-D bio-artificial tissue constructs made with collagen [4]. In this study, we made 3-D constructs using fibrin, and investigated whether VSMC morphology and mechanics are dependent on the ECM composition. Because previous studies have shown that VSMCs respond to cyclic stretch by increasing alignment and extra-cellular matrix production[5], we measured the mechanical responses of the VSMCs under continuous cyclic stretch.
Finite Element Analysis of the Knee: The Effect of Tibiofemoral Alignment and Weight on the Stresses in the Knee
Authors: Yang N. H. , Hashemi H. N. , Canavan P.
Published: March 2014

Osteoarthritis (OA) is a degenerative disease of articular cartilage that affects millions of people [1]. Local biomechanical factors may severely affect the initiation and progression of OA due to changes in loading conditions at the knee cartilage. Body weight and the frontal plane tibiofemoral alignment are two biomechanical factors that could increase the overall loading at the knee. A normal knee will have a tibiofemoral angle approximately 7° valgus [2]. Deviation from this angle leads to a knee joint with a varus or valgus condition. The tibiofemoral angle is measured by the intersection made between the mechanical axis of the femur and the tibia in the frontal plane and affects the magnitude of the varus knee moment, Fig. 1A. Biomechanical studies have shown the varus moment is a key determinant in the load distribution at the knee [3, 4], Fig. 1A, and has been linked to OA progression [5, 6].
A Strain Rate Dependent Constitutive Model for Liver Tissue: Experiments and Modeling
Authors: Roan Esra , Vemaganti Kumar
Published: March 2014

The mechanical characterization of liver tissue can be highly beneficial in the management of liver diseases and injuries (1). Liver is the most frequently injured abdominal organ due to injuries that are generally caused by motor vehicle accidents and falls from heights, both of which result in rapid decelerations (2). Moreover, in the US alone, more than 20,300 people die each year as a result of complications arising from chronic liver diseases and the associated fibrosis and cirrhosis.
Fluorescence Resonance Energy Transfer Between a Fluorescent Protein and Commercially Available Quantum Dots
Authors: Dennis Allison M. , Bao Gang
Published: March 2014

Semi-conductor quantum dots (QDs) are exceptionally bright fluorescent emitters that have garnered much attention over the past decade as an emerging tool for biomedical investigations. QDs offer several advantages over organic fluorophores, including up to 1,000-fold higher brightness than most organic fluorophores, very photostable, the “tunable emission” allowing for desired emission spectrum, and the ability to excite almost all QDs by a single (UV) wavelength [1,2]. The QDs typically used in the visible wavelength range are CdSe/ZnS core-shell nanoparticles; the CdSe center confers the particle its unique optical properties, while the ZnS shell serves as a passivation layer, protecting the core from oxidation and enhancing the quantum yield. In addition, an organic coating is necessary in order to confer water-solubility to the QD for biological studies [1,2].
The Effect of Aortic Endovascular Graft Oversizing on Barb Penetration and Fixation Strength
Authors: Kratzberg Jarin A. , Barnhart William , Golzarian Jafar , Raghavan Madhavan L.
Published: March 2014

Endovascular repair of abdominal aortic aneurysm (AAA), where an endovascular graft (EVG) — a stented vascular graft — is implanted intraluminally into the AAA has shown excellent short term outcome. However, long term outcome of implanted EVGs is fraught with new complications, the most severe of which is endoleak from graft migration, which can lead to re-pressurization of the AAA and potentially rupture. Graft migration is defined as the distal drift of an implanted EVG of 5mm or more from its initial anchor site (Figure 1). There have been many design changes to help decrease the rate of EVG migration including the addition of proximal attachment barbs to grafts to help secure them to the aortic wall. However, studies show that freedom from migration rates have not significantly increased for those grafts containing barbs compared to grafts without barbs [1]. We believe that controlled studies of endovascular graft parameters can lead to improvements in its design that increase graft attachment strength and hence decrease the risk of migration. The aim of the current study was to assess a key design variable in barbed grafts namely, graft oversizing (GO), defined as the ratio of expanded graft dia to aorta dia. We sought to assess the relationship between GO and attachment strength in barbed EVGs. Specifically, we hypothesized that a high GO will impede the ability of the EVG barbs to effectively penetrate the aortic wall.
Dynamics of the Aortic Valve Under Normal, Flow Rate-Varied and Heart Rate-Varied Conditions: An In Vitro Study
Authors: Yap Choon Hwai , Dasi Laksmi Prasad , Rusly Roy Junius , Yoganathan Ajit P.
Published: March 2014

Aortic valve (AV) disease caused by calcific stenosis is one of the major causes of cardiac related deaths around the world. Studies indicate that abnormal hemodynamics and structural stress fields experienced by the valve leaflets could cause tissue inflammation, which could lead to leaflet calcification and sclerosis [1,2]. However, the mechanics and dynamic properties of the aortic valve under various hemodynamic conditions have not been fully characterized, preventing us from further investigation of this link between mechanics and valve pathology.
Simulations of the Hinge Flow Fields of a Bileaflet Mechanical Heart Valve Under Physiologic Pulsatile Aortic Conditions
Authors: Simon Hélène A. , Ge Liang , Borazjani Iman , Sotiropoulos Fotis , Yoganathan Ajit P.
Published: March 2014

Native heart valves with limited functionality are commonly replaced by prosthetic heart valves. Since the first heart valve replacement in 1960, more than three million valves have been implanted worldwide. The most widely implanted prosthetic heart valve design is currently the bileaflet mechanical heart valve (BMHV), with more than 130,000 implants every year worldwide. However, studies have shown that this valve design can still cause major complications, including hemolysis, platelet activation, and thromboembolic events. Clinical reports and recent in vitro experiments suggest that these thrombogenic complications are associated with the hemodynamic stresses imposed on blood elements by the complex non-physiologic flow induced by the valve, in particular in the hinge region.
Evaluation of Polylactic Acid/Beta-Tricalcium Phosphate Scaffolds as Segmental Bone Graft Substitutes
Authors: Yanoso Laura , Jacobson Justin , Dadali Tulin , Reynolds David , Awad Hani
Published: March 2014

The use of processed structural allografts for treatment of massive segmental defects in long bones can be complicated by poor incorporation and remodeling of the devitalized graft, foreign-body reaction and micro-damage accumulation which often leads to catastrophic graft failure [1]. It is therefore useful to develop a bioengineered, biodegradable scaffold that is able to stimulate healing of the defect region. The use of bioengineered scaffolds has been limited due to their poor mechanical strength that does not permit withstanding large in vivo loads and due to their poor osteoinductive properties. We therefore investigated the use of rigid polylactic acid/beta-tricalcium phosphate (PLA/βTCP) composites used in conjunction with osteoinductive factors such as growth hormones (parathyroid hormone (PTH)) and growth factors (bone morphogenic protein-2 (BMP-2) & vascular endothelial growth factor (VEGF)) to stimulate bone formation and vessel ingrowth in the segmental defect region. We examined the physical characteristics of the scaffolds, and evaluated their osteoinductive potential in a clinically-relevant mouse model of a femoral segmental defect with or without PTH treatment. Finally, we used an ectopic bone formation model to assess the efficacy of the scaffold in site-specific delivery of bone anabolic factors.
Mechano-Regulation of Stem Cell Differentiation During Bending Stimulation of a Healing Bone Defect
Authors: Hayward Lauren N. M. , Morgan Elise F.
Published: March 2014

Mechanical stimulation of a bone fracture can alter the course of tissue differentiation [1]. Quantitative characterization of this mechano-regulatory effect has great therapeutic potential. For example, mechano-regulation theories are already being applied to tailor scaffold designs in tissue engineering applications [2]. Approaches such as these may lead to improved treatment of bone and joint degeneration as well as treatment of orthopedic injuries.
Damage Accumulation Model of Prosthetic Heart Valves in Forward and Reverse Flow Phases
Authors: Alemu Yared , Xenos Michalis , Deng Yuefan , Feng Rui , Einav Shmuel , Bluestein Danny
Published: March 2014

A highly resolved 3D geometry of a bileflet mechanical heart valve (MHV) was constructed to study the contribution of the forward and regurgitant flow phases to platelet damage. Platelet stress accumulation during repetitive passages past the valve was calculated using a damage accumulation model in pertinent trajectories. Additionally a discrete particles dynamics (DPD) multiscale modeling approach, which widely departs from the traditional continuum approach, was applied to this MHV geometry. It generated viscous blood flow velocity distributions, and is envisioned to further facilitate multiscale simulations of flow induced thrombogenicity in blood recirculating devices.
Modeling Shear Behavior in the Annulus Fibrosus
Authors: Hollingsworth Nathaniel T. , Wagner Diane R.
Published: March 2014

An accurate constitutive law for the annulus fibrosus (AF) is critical to modeling the complex loads and deformations of the intervertebral disc. In the healthy disc, the loads applied to the AF are primarily a combination of tension and torsion. Several researchers [1–5] have developed nonlinear strain energy functions to model the AF using the fiber-reinforced composite theory of Spencer [6]. However, a limitation to these previous studies is that they did not include shear data in calculating the model coefficients. Although many of these models have non-physical representations of the stress contribution of the collagen fibers [1, 2, 4], (i.e. collagen fibers only support tensile loads, but in the models they also support compressive axial loads), others have implemented a tension-only restriction for collagen fibers [3, 5]. The objective of this study was to model shear behavior of the AF in addition to previously modeled loading conditions [2]. The currently proposed model includes shear data in determining model coefficients. Additionally, we examined the effect of a tension-only representation of collagen fibers on the model’s fit to the experimental data.
Modeling Fluorescence Recovery After Photobleaching in Cyclically Loaded Bone: Potential Application in Quantitatively Measuring Load-Induced Solute Flows
Authors: Zhou Xiaozhou , Novotny John E. , Wang Liyun
Published: March 2014

Recent experiments strongly suggest that osteocytes, the most numerous bone cells, play much more active roles in bone adaptation and metabolism [1]. These multifunctioning cells are found to detect external mechanical stimuli, and to release soluable agents that modulate the functioning of other cell types [1, 2]. Solute transport around osteocytes through the bone lacunar-canalicular system (LCS), especially via load-induced convection, is critical for osteocyte viability and proper functioning. However, despite of significant advance in elucidating the LCS microstructure, permeability, and the molecular sieving properties [3–5], the fundamental mechanisms of solute transport around osteocytes still remain poorly understood, and solute flows have not been quantified in vivo.
The Dependence of Mechanical Properties of Adult Rat Myocytes on Cell Alignment
Authors: Liu Honghai , Yun Julie X. , Pirlo Russel K. , Dean Delpine , Yao Hai , Laberge Martine , Gao Bruce Z.
Published: March 2014

In response to damage, stress and cell death cardiac muscle undergoes remodeling in which cardiomyocytes de-differentiate and re-differentiate. An understanding of the mechanisms involved in this process may lead to therapies to promote and enhance the repair of damaged cardiac tissue. However, due to the complexity of native environments, it is hard to investigate this remodeling process directly on tissues isolated from the body. Therefore, it is important to construct a cell-culture model that will replicate the most relevant characteristics of that tissue in controlled environments with greater capability to be assessed. Native cardiac myocytes have an aligned arrangement in which neighboring cardiomyocytes are electrically and mechanical coupled through contact junctions. When adult cardiomyocytes are placed into a culture dish, the cells will be randomly oriented and lose their native phenotypes gradually due to the lack of proper aligned cell-cell connections. To address this issue, we have implemented our laser cell micropatterning system to create an adult cardiomyocyte culturing model with aligned rows of cells connected end to end. In this abstract, we describe the experimental procedure to achieve the laser alignment of adult cardiomyocytes and the results of mechanical property testing of the myocytes investigated using Multimode Picoforce Nanoscope Atomic Force Microscope (AFM) (Veeco).
Comparison of the Mechanical Properties of the Intraluminal Thrombus in Abdominal Aortic Aneurysms and Thrombus Mimics
Authors: Ashton John H. , Haskett Darren G. , Vande Geest Jonathan P.
Published: March 2014

An intraluminal thrombus (ILT) forms along the inner layer of the aorta in 75% of abdominal aortic aneurysms (AAAs) [1] and can often times cover a large surface area of the AAA wall. Mechanical modeling of the ILT is essential in many AAA studies. For example, inclusion of the ILT in rupture risk models significantly affects the estimated stress acting on the aneurysmal wall [2]. In addition, using ILT mechanical properties to model fluid flow through the ILT is critical to developing an intraluminal drug delivery treatment of AAAs to ensure the drug reaches the aneurysmal wall.
Syngas Laminar Burning Velocity: Comparison Between the Schlieren Photography and Spherical Bomb Methods
Authors: Monteiro Eliseu , Sotton Joulien , Labouda Serguei , Bellenoue Marc , Moreira Nuno Afonso , Malheiro Salvador
Published: March 2014

Gasification is a thermochemical process which can be defined as the conversion of an organically derived, carbonaceous feedstock by partial oxidation[1]. Typical gas product (syngas) includes mainly H2, CO, CO2, CH4 and N2, when air is used as oxidizing agent.
Comparison Between Isotropic and Anisotropic Electrical Properties of a DTI-Based Cardiac Model
Authors: Saaibi Ana Maria , Chang Isaac , Hwang Min-Sig , Sarntinoranont Malisa
Published: March 2014

Cardiac function is influenced by the three-dimensional organization of the myocardial fibers. Cardiac fibers are arranged in a circumferential, longitudinal, and a sheet-like fashion, forming counter-wound helices from the base to the apex of the heart. This fiber organization is responsible for the delicate balance between mechanical and electrical functioning of the heart. When electrical disruption of this coordinated function occurs, this is associated with cardiac arrhythmias which may lead to more serious conditions like ventricular fibrillation.
Use of Raman Microspectroscopy to Study Partioning of Molecules During Freeze-Processing of Protein Solutions
Authors: Dong Jinping , Hubel Allison , Bischof John C. , Aksan Alptekin
Published: March 2014

Biostabilization processes, based on desiccation, cooling or freezing, are surface-induced and thus are inevitably governed by scale-dependent kinetic constraints. During processing, these kinetic constraints induce heterogeneity (solute, and solvent concentration gradients, thermal gradients, and eventually, phase separation in the medium). During freezing, ice crystallization induces thermal (due to latent heat release), and concentration gradients (due to solute rejection) causing phase separation in the medium (i.e., formation of regions at different thermodynamic states). For example, during a typical cryopreservation application initially the bulk water freezes, increasing the concentration of the solutes in the rest of the unfrozen solution. Upon further cooling, the freeze-concentrated solution may also vitrify (or some constituents may crystallize), creating at least two distinct regions within the same medium with two distinct states.
Simulation of Optimal Surgical Anastomosis of Pediatric Aortic Cannula
Authors: Drummond Arielle , Dur Onur , Pekkan Kerem , Antaki James
Published: March 2014

Ventricular assist devices (VADs) have received widespread application to treat adults with end-stage heart failure. However, application to the pediatric population has been limited due to the excessive size; and therefore miniature, pediatric VADs (PVADs) are now being developed for the pediatric population to expand the current treatment options available to young patients with congenital heart defects and acquired heart disease. These pumps are typically connected via the left ventricular apex (via an inflow cannula) to the ascending aorta (via an outflow cannula). The distal anastomosis between outflow cannula and aorta has been studied by other researchers [1, 2] revealing complex fluid dynamic phenomena due to the non-physiologic confluence of native blood flow and outflow from the VAD. The corresponding pediatric anastomosis differs in dimensions and proportions to the adult, and has not yet been studied. The objective of this initial study is to examine the influence of cannula design, location, angle of insertion, and flow rate on the macro- and micro-fluid dynamics in the pediatric aorta. This parametric study is intended to provide both developers and surgeons with insight that would lead to optimization of both the cannula and surgical procedure, with particular emphasis at avoiding recirculation and stagnation flows commonly associated with platelet activation and thrombus generation [2, 3].
Risk Assessment of Cerebral Aneurysm Rupture and Regrowth
Authors: Childress Emily M. , Yarborough Christina , Hyun Sinjae , Ulm Arthur J. , Robinson Joe Sam
Published: March 2014

Cerebral aneurysms are dilatations in blood vessels of the brain. It is estimated that approximately 10 in every 100,000 persons per year has cerebral aneurysms and it occurs most often in people between ages 30 and 60 years [1]. Of these, roughly 27,000 patients per year are reported to have ruptured aneurysms. Since ruptures can lead to such conditions as central nerve system (CNS) hemorrhages in subarachnoid and intraparenchymal spaces, the chance of survival, once this occurs, is 50%.
Inhibition of Bone Loss and Muscle Atrophy by Dynamic Muscle Contractions With Rest Periods in a Functional Disuse Mouse Model
Authors: Ali Adiba , Qin Yi-Xian
Published: March 2014

Osteoporosis, induced by aging and long-term disuse, often occurs together with muscle loss. Musculoskeletal disuse causes severe physiologic changes and it has been proposed the synergistic effects of muscle function and bone adaptation. Bone fluid flow has been shown to be induced during mechanical loading, and is proposed to be a critical mediator of bone adaptation. The skeletal muscle may serve as a muscle pump that may mediate bone mechanotransduction via modulation of intramedullary pressure. Thus, muscular stimulation is proposed to be used to simultaneously treat both muscle and bone loss, but the optimal parameters required for such treatment is unclear. Studies have separately investigated the optimal signal parameters for bone or muscle. Insertion of recovery periods during high frequency stimulations have shown potential to reduce muscle atrophy by minimizing fatigue and mimicking physiologic contractions, and demonstrated enhancement of bone remodeling. Our preliminary research has indicated that dynamic muscle contractions within an optimal frequency range can significantly recover disuse induced bone loss. However, the optimal rest periods required to prevent muscle fatigue during stimulations are not clear. The overall objective of this study was to evaluate optimized dynamic muscle stimulations at relatively high frequency, e.g., 20 Hz, and to test the role of varying the rest duration on muscle mass and bone morphology in a functional hind limb disuse mouse model.
Molecular Mobility in Trehalose Loaded Mammalian Cells: Time-Resolved Fluorescence Anisotropy Measurements
Authors: Chakraborty Nilay , Parker Wesley , Elliott Kevin E. , Smith Stuart T. , Moyer Patrick J. , Elliott Gloria
Published: March 2014

Many preservation methods have utilized sugars such as trehalose as protectants against injury during cell preservation processing, especially during drying (1–5). As mammalian cells do not synthesize trehalose, research in the mammalian cell desiccation field has focused on the development of strategies to enable trehalose delivery into the intracellular milieu. Numerous techniques have been explored ranging from microinjection (2) to the creation or utilization of membrane pores (1,3). Fluid phase endocytosis has shown great promise as an effective strategy for non-invasively delivering water-soluble materials into the intracellular space (4, 5). In this technique trehalose is transported across the cell membrane in membrane-bound cellular compartments called endosomes. Cells incubated in cell culture medium containing trehalose have been shown to take up considerable amounts of trehalose by this technique (4, 5). How much of this trehalose actually become available for protection of biomolecules during the dehydration process has yet to be determined.
Fibroblasts Induce Mechanical Changes in the Extracellular Environment and Enhance Capillary-Like Network Formation
Authors: Hurley Jennifer R. , Narmoneva Daria A.
Published: March 2014

Cardiac tissue engineering studies have demonstrated the importance of revascularization in engineered grafts for successful implantation and regeneration [1]. Understanding the myocardium’s complex cellular organization and the interactions between the major cardiac cell types (cardiomyocytes, endothelial cells, and cardiac fibroblasts) is critical for revascularization. Our previous studies have shown the importance of cardiomyocyte-endothelial interactions [2]. However, there is limited information available on endothelial-fibroblast interactions. We and others have previously observed that during capillary assembly, fibroblasts provide chemical signaling via expression of growth factors [3, 4]. In addition, fibroblasts may also regulate angiogenesis through alterations to the mechanical environment via myocardial remodeling, including matrix degradation and deposition, and tissue contraction. Changes to the extracellular mechanical enviroment may lead to changes in basic cell functions such as proliferation, apoptosis, and growth factor expression.
Mechanical and Chemical Stimulation of Bone-Marrow Stem Cells in a Three-Dimensional Fibrin Matrix: Preliminary Results
Authors: LoSurdo Jessica L. , Chew Douglas W. , Nieponice Alejandro , Vorp David A.
Published: March 2014

The primary goal of tissue engineering is to develop a biological, mechanically-robust, and anti-thrombogenic vascular graft to replace diseased or damaged tissue and organs [1]. For example, researchers have incorporated smooth muscle cells (SMCs) into extracellular matrix to provide a living, functional conduits with the intended purpose of replacing SMC-containing tubes, such as the blood vessel, urethra, esophagus, intestine, etc. Although the preferred source is autologous cells to avoid immunological rejection, adult SMCs are difficult to obtain and expand. An alternative source of autologous cells could be bone marrow derived stem cells (BMSCs), which differentiate toward mesenchymal and hematopoietic lineages [2].
Detection of Myocardial Fiber Disruption in Artificial Lesions With 3D DT-MRI Tract Models
Authors: Zhang Song , Crow John A. , Cooper Robert C. , McLaughlin Ronald M. , Burgess Shane , Borazjani Ali , Liao Jun
Published: March 2014

In the United States, it is estimated that in 2008 approximately 1.2 million people will suffer a new or recurrent myocardial infarction. In 2005, the latest full year for which statistics are available, 16 million Americans (7.3% of the population) had some form of coronary heart disease. Loss of myocardium as a result of myocardial infarction increases wall stress locally and globally and triggers adaptive responses at the molecular, cellular, and tissue levels. These adaptive responses can lead to left ventricular dilation and congestive heart failure. Accurate non-invasive evaluation of myocardial structural degeneration (damage) and left ventricular remodeling following an infarct would have both prognostic and therapeutic value clinically.
A Robotic Dynamic Activity Simulator: Design, Performance and Application
Authors: Sharkey Neil A. , Hoskins Andrew H.
Published: March 2014

The mechanics and physiological processes that produce human locomotion are most commonly measured using non-invasive techniques that limit potential risks to subjects or patients. The complex mechanics of the foot and ankle during dynamic events often cannot be determined from information provided by these techniques and a deeper understanding is necessary to more effectively diagnose and treat pathologic conditions. This has prompted many researchers to turn to alternative techniques, in most cases either numerical simulation employing computational models or physical laboratory models that load or re-animate cadaver limbs procured from conscientious donors.
Cardiogenesis of Embryonic Stem Cells is Modulated by Hydrodynamic Mixing Conditions
Authors: Sargent Carolyn Y. , Hiatt Luke A. , Anantharaman Sandhya , Berson Eric , McDevitt Todd C.
Published: March 2014

Embryonic stem cells (ESCs) have the potential to differentiate into all somatic cell types and are uniquely capable of differentiating into functional cardiomyocytes; however, to effectively use ESCs for cell-based therapies to regenerate viable myocardial tissue, an improved understanding of mechanisms regulating differentiation is necessary. Currently, application of exogenous factors is commonly attempted to direct stem cell differentiation; however, progression towards controlling multiple environmental factors, including biochemical and mechanical stimuli, may result in increased differentiation efficiency for clinical applications. Additionally, current methods of ESC differentiation to cardiomyocytes are labor-intensive and produce relatively few cardiomyocytes based on initial ESC densities. Rotary suspension culture to produce embryoid bodies (EBs) has been shown to yield greater numbers of differentiating ESCs than static suspension cultures [1]. Thus, the objective of this study was to examine how the hydrodynamic mixing conditions imposed by rotary orbital culture modulate cardiomyocyte differentiation.
Experimental and Computational Investigation of the Poroviscoelastic Response of Engineered and Native Ligament
Authors: O’Connor Devin T. , Ma Jinjin , Narayanan Harish , Garikipati Krishna R. , Arruda Ellen M. , Grosh Karl
Published: March 2014

Experiments on explanted soft tissue and collagen gels [1], and the theory of soft tissue mechanics [2], indicate that the important mechanisms by which soft collagenous tissues deform and develop stress include elasticity, viscoelasticity and poroelasticity. These contributions to the mechanical response are directly modulated by the content and morphology of collagen, elastin, other molecules such as proteoglycans and glycosaminoglycans, and fluid, which is water. Our engineered collagenous constructs demonstrate histological and mechanical characteristics of native tendon and ligament of different levels of maturity. In order to evaluate whether the constructs have optimal mechanical function for implantation and utility for regenerative medicine, the relation must be established between the content and morphology of collagen and elastin, and the elastic, viscoelastic and poroelastic response of the engineered collagenous constructs at these different developmental levels.
Comparison of Right Ventricular Stroke Work for Tetralogy Patient and Normal Subject
Authors: Das Ashish , Gottliebson William , Banerjee Rupak K.
Published: March 2014

Tetralogy of Fallot (TOF), also called blue-baby syndrome is one of the most common congenital heart defects in children after infancy and is estimated to account for 10% of all congenital heart defects [3]. TOF consists of four interrelated lesions: i) ventricular septal defect ii) Pulmonary stenosis iii) Right ventricular (RV) hypertrophy and (iv) Overriding Aorta [3]. TOF has been successfully repaired for several decades (Fig. 1). There are now an estimated 100,000 adult “repaired TOF” patients in the United States alone. As a result, long-term sequelae of the disease and repair have become important clinical issue. Specifically, residual pulmonary valve insufficiency (PI) is one such accepted and often unavoidable sequela. PI, when severe, abnormally alters the RV loading conditions, thereby triggering RV hypertrophy and dilatation. In turn, RV dilatation can evolve into irreversible RV myocardial contractile dysfunction, and has been related to sudden death in many “repaired TOF” patients. To normalize RV loading conditions, pulmonary valve replacement is often necessary and should be performed prior to the onset of irreversible RV myocardial damage.
Towards a Structurally Based Constitutive Model of Urinary Bladder Wall Tissue Remodeling After Spinal Cord Injury
Authors: Wognum Silvia , Sacks Michael S.
Published: March 2014

Spinal cord injury (SCI) is accompanied by urologic complications, characterized by two phases (early areflexic phase and late hyperreflexic phase), where the routine function of the urinary bladder of storing urine and voiding becomes compromised. In addition to functional deficiencies, these pathologies are often accompanied by changes in bladder wall tissue morphology and mechanical properties. Our experimental studies have revealed that the bladder wall can undergo rapid remodeling post-SCI (figs.1,2) and exhibits complex biomechanical responses (fig.2B) [1,2,3,4]. These remodeling events will result in profound changes in bladder wall biomechanical behavior (fig.2) and ultimately organ function. The specific alterations in mechanical behavior and functional properties of bladder wall tissue and the underlying mechanisms are not well understood. A multi-phase structural constitutive model of the bladder wall is clearly needed to understand how changes in various tissue components produce observed changes in bladder function.
Biomechanical Comparison of Open Transosseous Versus Arthroscopic Suture Anchor Repair of the Subscapularis Tendon
Authors: Wheeler Daniel J. , Garabekyan Tigran , Lugo Roberto , Buckley Jenni M. , Lotz Marielena , Lotz Jeffrey C. , Ma C. Benjamin
Published: March 2014

There has been interest in improving arthroscopic subscapularis repairs due to their popularity and efficacy when compared to open subscapularis repairs. However, previous biomechanical analyses of rotator cuff repairs have typically focused on the supraspinatus tendon [1–5]. Testing repair techniques in the subscapularis tendon requires the modification of previously established biomechanical testing methods. Most rotator cuff tendon tests have utilized axial loading on supraspinatus and infraspinatus tendons [1–4]. Most subscapularis tendons are torn with forced external rotation of the shoulder. Axial loading of the subscapularis tendon would not be representative of the injury mechanism. Additionally, past rotator cuff studies have employed a variety of techniques for clamping tendons, including freezing clamps and soft tissue grips. Such methods offer insufficient fixation for tendons that have high muscle content, such as the subscapularis. Several studies have focused on the repair’s ability to restore the appropriate healing environment at insertion footprint. These investigations have used either digitizers or pressure-sensitive film to measure contact area [5–7]. However, there are questions concerning the repeatability and accuracy of the results provided by these techniques. The objective of this study was to compare the biomechanical performance of open, transosseous fixation with that of the arthroscopic, suture anchor technique for subscapularis repair, while making three specific improvements to current testing methods. It sought to: 1) apply physiologically accurate loads to the subscapularis using cyclic, external rotation, 2) identify an effective method of clamping tendons with high muscle content, such as the subscapularis, and 3) introduce a novel, tactile pressure measurement system that measures contact pressure and area in real-time.
Extracellular Matrix-Contractile Response Coupling of the Aortic Heart Valve Interstitial Cell
Authors: Schmidt David E. , Merryman W. David , Sacks Michael S.
Published: March 2014

The role of aortic valve interstitial cell (AVIC) and extracellular matrix (ECM) interactions of the aortic valve (AV) are not well understood. Distinct differences in the composition and structure of the AV leaflet layers (fibrosa and ventricularis) have been shown to influence mechanical properties 1. Our ability to measure the effects of changes in cellular stiffness in the dense collagenous AV leaflets (AVL) 2 offers a unique opportunity to explore the in-situ AVIC stiffness and local AVIC-ECM mechanical interactions. In the present study, a multi-scale finite element model approach was developed based on our simulations of our flexural stiffness experiment 2 were used to develop effective layer dependent mechanical properties. In addition, we present a predictive model for the alteration of AVL tissue mechanical properties resulting from AVIC contraction. This model provides a means to probe the layer dependent properties under the influence of AVIC contraction relative to an intact tissue state. By establishing a procedure to examine ECM stiffness in situ, through coupled experimental and computational methods, insights into relative contributions of ECM components were developed. Finally, in contrast previous study, where tissue stiffness was reported in terms on an instantaneous elastic modules, this work provides a more complete mechanical response of AVL in flexure.
Simultaneous Determination of Skeletal Model Parameter Values, Motions, and Controls From Noisy Measurement Data
Authors: Fattey Michael G. , Fregly Benjamin J.
Published: March 2014

Accurate model parameter value and motion determination is important for obtaining reliable results from inverse dynamics analyses of gait. If the model parameters do not properly match their true values, the predicted motions and loads may lose their clinical significance [1]. Typical approaches to biomechanical model parameter estimation have included the use of scaling rules based on cadaver studies [2] and the use of multi-level optimization routines [3,4]. However, scaling rules do not provide optimal parameter estimates, and multi-level optimization techniques are computationally expensive.
On the Intracellullar Memory of Stress Fiber Orientation: Effects of Microtubules and Focal Adhesions on the Repolymerization Process of Stress Fibers
Authors: Yang Yunfeng , Nagayama Kazuaki , Matsumoto Takeo
Published: March 2014

Stress fibers (SFs) play essential roles in various cellular functions such as cell movement, shape maintenance and cell division [1]. One of their key features is that they dynamically change their structures in response to mechanical environment to which they are exposed [2]. For example, cultured endothelial cells exposed to cyclic stretch preferentially reorganize their actin stress fibers to the direction in which the strain magnitude of the fibers become minimum [3].
Local Release of Metallic Ions From Stents Into Vascular Tissue and Associated Alterations of Stent Surfaces
Authors: Halwani Dina O. , Anderson Peter G. , Brott Brigitta C. , Anayiotos Andreas S. , Lemons Jack E.
Published: March 2014

In-vivo corrosion of endovascular stents presents two main risks; release of metallic debris and deterioration of the mechanical properties of the stents which may lead to fracture. Retrieval analysis of explanted nickel-titanium (NiTi) aortic stent grafts showed pitting corrosion and fracture of the NiTi wire component [1, 2].
Imaging of Aortic Valve Collagen Structure and Internal Deformations Using a Novel Digital Image Correlation Technique
Authors: Doehring Todd C. , Kahelin Michael
Published: March 2014

Advancements in optics and digital imaging tools have often led to new insights into tissue structure. Newly available computer controlled lcd polarizing filters have provided unprecedented control over light waveforms and structure. Inexpensive digital cameras have many times greater color sensitivity. Our goal is to apply these new technologies to quantitative imaging of aortic valve structures in-situ. We have developed a new elliptically polarized light imaging system (EPLIS) and technique for imaging aortic valve tissues. This new technique reveals takes advantage of the birefringent property of collagen to reveal multi-layered collagen fiber and membrane valve structures that were previously unknown. Using digital imaging correlation (DIC) image analysis software (developed in-house), the new imaging technique allows direct measurement of the internal deformations of aortic valve specimens during controlled loading. We present our imaging and analysis techniques, along with time-lapse images showing the complex structure of the aortic valve and direct measurements of deformations under controlled loads.
Urothelial Biomechanics: Submucosal Sensing of Intravesical Pressure
Authors: Fletter Paul C. , Zaszczurynski Paul J. , Damaser Margot S.
Published: March 2014

Measurement of physiological pressures is fundamental to many forms of medical diagnosis and monitoring in the cardiovascular, respiratory, gastrointestinal, urological and other systems. Pressure is usually measured via catheters, either connected to transducers outside the body or more recently by micro-transducers mounted on the tip of such catheters. However, this requires that the catheters be inserted and maintained without infection and that the patient be tethered to a recording device. While this may be manageable during short term tests such as urodynamics, the measurement of bladder pressure to diagnose incontinence, chronic monitoring poses an additional set of obstacles.