bluuebunny/crossref_metadata_2025 huggingface dataset:
Design From Nature: Kinematic Modeling of the Seahorse Tail
Authors: Praet Tomas , Adriaens Dominique , Rommens Thibaut , Masschaele Bert , Van Cauter Sofie , De Beule Matthieu , Verhegghe Benedict
Published: July 2013

Through billions of years of evolution, nature has produced remarkably elegant solutions to a whole range of real-world problems. An increasing number of engineers is turning towards nature for design inspiration, as the evolutionary adaptation of organisms is in many ways comparable to the design cycle used in engineering: changes in functionality are tested on their fitness and thereafter either reinforced or rejected.
Could Substrate Stiffness and Oxygen Tension Regulate Stem Cell Differentiation During Fracture Healing?
Authors: Burke D. , Kelly D. J.
Published: July 2013

Extrinsic mechanical signals have been implicated as key regulators of Mesenchymal Stem Cell (MSC) differentiation [1]. It has been possible to test different hypotheses for mechano-regulated differentiation by attempting to simulate regenerative events such as bone fracture repair [2]. During such events, repeatable spatial and temporal patterns of tissue differentiation occur. More recently, in vitro studies have identified other environmental cues, such as substrate stiffness [3] and oxygen tension [4], as key regulators of MSC differentiation. The hypothesis of this study is that a computational model that assumes substrate stiffness and oxygen tension regulate stem cell differentiation can be used to predict the spatial and temporal patterns of tissue differentiation that occur during fracture healing.
Differentiation and Dynamic Tensile Loading Alter Nuclear Mechanics and Mechanoreception in Mesenchymal Stem Cells
Authors: Heo Su-Jin , Nerurkar Nandan L. , Driscoll Tristan P. , Mauck Robert L.
Published: July 2013

Mesenchymal stem cells (MSCs) are a promising cell source for tissue engineering applications, given their ease of isolation and multi-potential differentiation capacity [1]. Passive and active mechanical signals can direct MSC lineage commitment [2], however, the subcellular machinery that translates physical cues to biologic response remains unclear. Direct deformation of the nucleus may influence differentiation by inducing mechanical reorganization of nuclear chromatin. Because the nuclei of differentiated cells are stiffer than progenitor cells [3], it is possible that such mechanoregulatory mechanisms vary with differentiation state. Lamin A/C is a filamentous protein that largely defines nuclear shape, size and stiffness [3]. Recent work suggests that Lamin A/C also regulates chromatin organization and transcriptional activity [4]. Recently, we have developed an in vitro system to direct the functional differentiation of MSCs into fibrochondrocytes, using electrospun polymeric nanofiber substrates [5]. Alignment of nanofibers directs cell alignment, allowing external forces to be applied uniformly along the long axes of cells, emulating the mechanical microenvironment experienced by embryonic progenitors during fibrous tissue morphogenesis [6]. We have noted, however, that as MSCs undergo fibrochondrogenesis, translation of scaffold deformation to nuclear deformation is attenuated [7]. From those studies, it was not clear whether this was due to changes in cellular mechanics or to accretion of extracellular matrix during differentiation. Thus the objective of the present work was to specifically identify how fibrochondrogenesis of MSCs on aligned nanofibrous scaffolds alters nuclear mechanics and mechanoreception, and further to ascertain whether mechanical stimulation alone can elicit similar mechanoregulatory changes.
A Quantitative Comparison Between Baseline Hemodynamics and End-Stage Aneurysm Formation in ApoE −/− Mice
Authors: Trachet Bram , Renard Marjolijn , De Santis Gianluca , Staelens Steven , De Backer Julie , Antiga Luca , Loeys Bart , Segers Patrick
Published: July 2013

The pathogenesis of abdominal aortic aneurysm (AAA) formation still remains debated. Hemodynamics have been suggested to play a (modulating) role, but no follow-up studies have been performed due to (a.o.) a lack of human data before disease initiation. We therefore used an established mouse model of AAA [1] to study whether AAA develops at locations experiencing disturbed flow. We set up a framework to obtain mouse-specific Computational Fluid Dynamics (CFD) simulations of the mouse abdominal aorta, combining: (i) an in vivo assessed geometric model [2] and (ii) in vivo measured boundary conditions. A distance map was generated to link baseline and end-stage aortic morphologies after AAA development, and the relationship between baseline hemodynamics and end-stage dilatation was quantified.
Feasibility of Highly Constrained Muscle Force Predictions for the Knee During Gait
Authors: Walter Jonathan P. , D’Lima Darryl D. , Besier Thor F. , Fregly Benjamin J.
Published: July 2013

Accurate assessment of human muscle forces during walking could significantly aid in the analysis and treatment of common neuromusculoskeletal disorders such as osteoarthritis [1], stroke, and cerebral palsy. However, the inability to measure muscle forces in vivo along with the inability to calculate muscle forces directly has greatly hindered achievement of this goal. Due to its complexity, the knee is a particularly difficult joint for assessing in vivo muscle forces.
Stretch-Induced Stress Fiber Remodeling and MAPK Activations Depend on Mechanical Strain Rate
Authors: Hsu Hui-Ju , Locke Andrea , Vanderzyl Susan Q. , Kaunas Roland
Published: July 2013

Actin stress fibers (SFs), bundles of actin filaments crosslinked by α-actinin and myosin II in non-muscle cells, are mechanosensitive structural elements that respond to applied stress and strain to regulate cell morphology, signal transduction and cell function. Results from various studies indicate that myosin-generated contraction extends SFs beyond their unloaded lengths and cells maintain fiber strain at an optimal level that depends on actomyosin activity (Lu et al., 2008). Stretching the matrix upon which cells adhere perturbs the cell-matrix traction forces and cells respond by actively re-establishing the preexisting level of force (Brown et al., 1998; Gavara et al., 2008). We have developed a sarcomeric model of SF networks (Kaunas et al., 2011) to predict the effects of stretch on SF reorganization depending on the rates of matrix stretching, SF turnover, and SF stress relaxation.
Mechanisms of Abdominal Aortic Aneurysm Formation in Persons With Traumatic Amputation of a Lower Extremity
Authors: Smolensky Alexander V. , Clement-Guinaudeau Stephanie , Larche Michael K. , Oshinski John N. , Taylor W. Robert
Published: July 2013

Abdominal aortic aneurysms (AAA) are a major cause of morbidity and mortality in the US. The incidence of AAA in older Americans approaches 30%. The most common place of AAA is infrarenal abdominal aorta where oscillatory shear stress (OSS) is present. OSS is known to initiate an inflammatory response in the endothelium. It is known that there is up to a 5-fold increase in the occurrence of AAA in individuals with traumatic amputation of a lower extremity. This increased AAA occurrence is unrelated to co-morbid conditions. We recruited 3 healthy volunteers who underwent infrarenal abdominal aortic Magnetic Resonance angiography and phase contrast imaging. These measurements were done at base line and with acute arterial blood flow occlusion to lower extremity with a blood pressure cuff to mimic amputation. The collected data was used to calculate systolic forward and diastolic retrograde blood flow and wall shear stress during cardiac cycle. Our results suggest that mimicking amputation produces a nearly doubling of retrograde blood flow with ∼50% increase of negative WSS. These changes are more pronounced on the contralateral to the “amputation” side. We conclude that lower extremity traumatic amputations may lead to augmentation of OSS in infrarenal aorta causing AAA development.
Altered Mechanosensitivity Can Explain the Substantially Increased Bone Mass in Hypoparathyroidism
Authors: Christen Patrik , van Rietbergen Bert , Ito Keita
Published: July 2013

Hypoparathyroidism (HypoPTH) is characterized by low or absent parathyroid hormone (PTH). It is mainly associated with a drastic suppression of bone turnover by around 80% (Rubin et al., 2008) and a substantial increase in bone mass in the range of 10–32% (Rubin et al., 2008; Abugassa et al., 1993).
Positive and Negative Wall Shear Stress Gradients Have Different Effects on Endothelial Phenotype Under High Wall Shear Stress
Authors: Dolan Jennifer , Sim Frasier , Meng Hui , Kolega John
Published: July 2013

In both human and animal models, cerebral aneurysms tend to develop at the apices of bifurcations in the cerebral vasculature where the blood vessel wall experiences complex hemodynamics. In vivo studies have recently revealed that the initiation of cerebral aneurysms is confined to a well-defined hemodynamic microenvironment [1,2]. Metaxa et al. [2] found that early aneurysm remodeling initiates where the vessel wall experiences high wall shear stress (WSS) and flow is accelerating, thus creating a positive spatial gradient in WSS (WSSG). Closer examination of such in vivo studies reveals that exposure of the vessel wall to equally high WSS in the presence of decelerating flow, that is, negative WSSG, does not result in aneurysm-like destruction.
Shoulder Rotational Laxity is Related to Joint Loading During Throwing
Authors: Zheng Nigel , Wang Hongsheng , Eaton Koco
Published: July 2013

Throwing arm injuries are common and often related to shoulder rotational laxity. Both shoulder external and internal rotational laxity are often checked in a physical assessment. The shoulder external rotation of the throwing arm during physical assessment is reported to be about 10 degree greater than the non-throwing arm [1]. Throwing arm injuries often occur during throwing activities. High forces and torques were generated during throwing activity. Extremely high shoulder external rotation (about 180°) and high internal rotation velocity (over 7000°/s) during baseball pitching are reported [2].
On the Role of Modeling Choices in Estimation of Cerebral Aneurysm Wall Tension
Authors: Ramachandran Manasi , Hu Shouhua , Lu Jia , Laakso Aki , Harbaugh Robert E. , Raghavan Madhavan L.
Published: July 2013

Estimations of pressure-induced tension in the cerebral aneurysm sac wall may serve as metrics that help stratify patients according to rupture risk. Beyond segmentation of patient-specific aneurysm geometries, many modeling choices may be made in order to numerically estimate pressure-induced aneurysm wall tension. Some of these key choices are: 1) the material model and its parameters (this is unknown at a patient-specific level); 2) whether or not to accommodate bending deformation (membrane versus shell); 3) whether and how much of vasculature to include in domain of analysis; and 4) how to address the lack of zero-pressure geometry (forward versus inverse solution schemes). Often, the focus is on what the best of these modeling choices are. In an ideal world, appropriate modeling choices would be the use of an anisotropic finite elastic model [1–2], shell-like behavior [3], a large enough vasculature in the analysis domain to minimize edge-effects at the aneurysm sac, and an inverse solution scheme [3] to address the pre-deformed nature of the sac under in vivo imaging. But are these rigorous modeling choices really that necessary? Would compromising on these choices translate into significant error in the findings? We submit that, to the extent that the goal is to stratify patients according to sac wall tension, modeling choices are really secondary and will not translate into significant error in our interpretations. The objective of this study is to test the importance of three of these modeling choices — material model, truncation of vasculature in analysis domain and solution scheme (forward versus inverse) — in stratifying aneurysms based on wall tension using aneurysms in a study population.
Finite Element Analysis of Nutrient Distribution and Cell Viability in Intervertebral Disc: Effect of Compression and Degeneration
Authors: Jackson Alicia R. , Huang Chun-Yuh , Brown Mark D. , Gu Weiyong
Published: July 2013

The intervertebral disc (IVD) is the largest avascular structure in the human body. As such, important nutrients, such as glucose and oxygen, that are necessary for cellular survival and functioning, must be transported into the disc via diffusion. As a result, steep concentration gradients develop across the tissue, dependent upon both cellular demand (i.e., metabolism) and transport. Both mechanical loading and tissue degeneration may alter nutrient distributions in the IVD. This may, in turn, affect IVD cell activity and viability.
Influence of Heart Rate and Epicardial Stenosis Severity on Cardiac Contractility Under Concomitant Microvascular Disease in a Porcine Model
Authors: Peelukhana Srikara V. , Kolli Kranthi K. , Gottliebson William , Leesar Massoud , Helmy Tarek , Effat Mohamed , Arif Imran , Schneeberger Eric W. , Succop Paul , Banerjee Rupak K.
Published: July 2013

Invasive guide wire methods to assess functional severity of coronary stenosis are affected by dynamic variables like heart rate (HR), contractility, epicardial stenosis (AS) and blood pressure. The interdependence of these factors is also influenced by the presence of concomitant microvascular disease (CMVD). The purpose of this study is to assess the variation in contractility under varying HR and AS in the presence of CMVD. In vivo experiments were performed on seven Yorkshire pigs. It was found that, in the presence of concomitant microvascular disease (CMVD), for lower AS (<50%) contractility increases for HR<120 bpm while it marginally decreases for HR>120 bpm. However, for higher AS (>50%), contractility decreases for both HR<120 bpm and HR>120 bpm.
A Growth and Remodeling Approach to AAA Modeling: Feasibility and Initial Insights
Authors: Wilson John S. , Baek Seungik , Humphrey Jay D.
Published: July 2013

While the advancement and widespread use of medical imaging have greatly aided in the diagnosis of abdominal aortic aneurysms (AAAs), many questions remain regarding the natural progression of AAAs and most importantly predicting their likelihood of rupture — an event carrying a mortality rate of over 80% [1]. Current guidelines recommend surgical intervention when the aneurysm achieves a diameter of 5.5 cm [2]; however, it has been documented by at least one study of 161 consecutive patients that approximately 10% of AAA ruptures occur in aneurysms measuring 5 cm or less [3]. It is also unknown how many surgically repaired aneurysms may not have proceeded to rupture in a patient’s lifetime. For this reason, there is much interest in identifying better predictors of rupture risk than diameter alone.
The Effect of Intramedullary Stem Curvature on the Torsional Stability of Cemented Joint Replacement Systems
Authors: Hosein Yara K. , Clynick Meghan P. , Takaki Sarah E. , McLachlin Stewart D. , Dunning Cynthia E.
Published: July 2013

Joint replacement surgeries are a common treatment for diseased or damaged joints. The procedure typically involves the insertion of a metal stemmed component into the bone canal, either with or without bone cement, to achieve fixation to the host bone. Although this procedure has proven effective, implant loosening remains a relatively common complication, leading to pain and the eventual need for revision surgery.
Brain Tissue Modelling: Calibration and Validation of a Fractional Calculus Based Viscoelastic Constitutive Equation
Authors: Libertiaux Vincent , Cescotto Serge
Published: July 2013

Constitutive equations for biological tissues can be sorted in two categories: structural and phenomenological. The first approach is based on the microstructure of the tissue while the second relies on a macroscopic description. Due to the nature of the neural tissue, structural approach is rarely used. Meaney [1] proposed a model for the white matter of the brain.
Development, Pre-Clinical Validation of the UltraMag and Summary of the Clinical Experience With Levitronix Ventricular Assist System
Authors: Gellman Barry N. , Richardson J. Scott , Tuzun Egemen , Gempp Thomas M. , Harms Kelly M. , Fleischli Andreas , Moody Kimberly S. , Marks John D. , Conger Jeff L. , Kent Stella , Frazier O. Howard , Dasse Kurt A.
Published: July 2013

Over 6,500 cardiac and cardiopulmonary support patients have been treated worldwide with Levitronix “MagLev” support devices, including over 850 pediatric patients. The Levitronix CentriMag and PediMag systems are currently commercially available for short term clinical cardiopulmonary support applications. A new version of ventricular assist device, the UltraMag has been developed. The UltraMag is designed for VAD support of infants and adults. The UltraMag device is intended for use for up to 90 days of extracorporeal cardiac or cardiopulmonary support. This article describes this unique technology, preclinical validation, and reports on the worldwide clinical experience with all commercially available Levitronix support systems.
Intracranial Pressure Measurement Within the Rat Skull is Sensitive to Shock Wave Intensity and Weight of the Specimen
Authors: Bolander Richard , Bir Cynthia , VandeVord Pamela
Published: July 2013

Blast associated injuries have been quantified into different classes based on the type of trauma that they create [1]. Of these types of trauma, the neuropathology invoked by shock wave exposure is the most ambiguous [1]. The properties associated with shock wave exposure have lead to multiple hypothesized mechanisms for brain trauma including: acceleration-based damage, a thoracic squeeze resulting in pressure pulses to the brain, or transference of energy from the shock wave into the brain via the skull [2, 3].
PANC-1 Migration and Cluster Formation is Regulated by Short Range Mechanical Forces
Authors: Holfinger Steven , Reen Rashmeet , Ackerman William , Kniss Douglas , Gooch Keith J.
Published: July 2013

Islet cell transplantation has already shown improved control of glucose levels and the potential to achieve insulin independence in type 1 diabetes mellitus, however there is a shortage of organ donors needed to match patient needs [1–2]. In the search for alternative sources of islets, many cell types have shown signs of β-cell differentiation by secreting c-peptide, insulin, and glucagon [3–5]. When maintained in serum-free medium, human epithelial-like pancreatic adenocarcinoma (PANC-1) cells and human-islet derived precursor cells (hIPCs) can go through a morphological transition and cluster [6]. These islet-like cell aggregates subsequently express glucagon, somatostatin, and insulin, indicating that clustering may play an important role in differentiation towards β-cells [7].
The Effects of Extracellular Matrix Proteins and Stiffness on Neuronal Cell Adhesion
Authors: Kleiman Ross , Previtera Michelle , Parikh Sharan , Verma Devendra , Schloss Rene , Langrana Noshir
Published: July 2013

Spinal cord injuries have spurred research interests in finding ways to repair or replace damaged neurons. We are looking to find novel ways to promote proliferation and differentiation of stem cells in order to replace damaged spinal cord neurons. While previous studies have shown that the mechanical properties of the cellular environment influence proliferation and differentiation, these studies have only been performed on polyacrylamide and agarose gels (1, 2). Collagen gels provide the opportunity to promote neuronal precursor cell (NPCs) proliferation and differentiation in a more natural environment by utilizing the mechanical properties of the gel. In this study, we examine the effects of 2D collagen matrices of varying stiffness on proliferation and differentiation of rat, spinal cord NPCs in order to create a more biocompatible tissue-engineered platform.
Remodeling and Contractility of the Actin Cytoskeleton During the Shear Deformation of Single Chondrocytes
Authors: Dowling Enda P. , Ronan William , Deshpande Vikram S. , McMeeking Robert M. , Athanasiou Kyriacos A. , McGarry J. Patrick
Published: July 2013

Numerous in vitro studies have demonstrated that chondrocytes react to mechanical stimuli. Compression of chondrocytes in an agarose gel induces disruption of the actin cytoskeleton [1]. In addition, chondrogenic gene expression decreases for chondrocytes cultured in monolayer, while inhibition of actin polymerization causes an increase in type II collagen and GAG production [2]. Despite such extensive in vitro investigations, the mechanisms by which chondrocytes actively respond to mechanical loading are not well understood. Simple hyperelastic and viscoelastic computational cell models have previously been used to model chondrocytes. However, such passive models ignore the key biomechanisms by which cells sense and react to external loads, and hence offer limited insight or predictive capability [3].
Framework for Fluid-Structure Interaction Analysis of Aortic Coarctation Resulting From Proximal Protusion of Thoracic Aortic Stent Graft Into the Arch
Authors: Pasta Salvatore , Dur Onur , Cho Jae-Sung , Pekkan Kerem , Vorp David A.
Published: July 2013

Thoracic aortic stent grafts (TASG) are commonly used to repair aortic anomalies or diseases in a minimally-invasive fashion. One complication of TASG is collapse, whereby blood is unable to completely flow through the graft as intended. Most TASG collapses occur in the setting of endovascular repair of traumatic thoracic aortic transection, where a typically smaller diameter aorta of pediatric patients is repaired with a relatively larger diameter endograft designed to treat aneurysmal disease [1]. It is hypothesized that the poor apposition of the leading edge of the proximal stent graft to the lesser curvature of the aortic arch can result increased hemodynamic force at the leading side of the graft can reach sufficient magnitude to cause collapse and gradual occlusion of the tubular graft. The incidence rates of stent graft collapse in endovascular aortic transection repairs have been reported to range from 0.03% to 10% [2].
The Role of SRC in Strain- and Ligand- Dependent Phenotypic Modulation of Mouse Embryonic Fibroblasts
Authors: Sewell-Loftin M. K. , Merryman W. David
Published: July 2013

Connective tissue fibrosis represents a significant portion of mortality and morbidity in our society. These diseases include many illnesses such as heart valve disease, atherosclerosis, macular degeneration, and cirrhosis, meaning that millions of lives are affected by these conditions each year. Fibrotic tissues form when quiescent fibroblasts activate becoming myofibroblasts, the phenotype of active tissue construction and fibrosis. During this process, the cells produce smooth muscle α-actin (αSMA), a contractile element considered to be the hallmark of cellular activation [1]. Following the production of αSMA, there is an increase in the synthesis of extracellular matrix (ECM) proteins, most notably type I collagen; this increase in ECM proteins causes the stiffening of the tissue characteristic of fibrotic disease. In non-disease states (such as wound healing or tissue development), the myofibroblasts will either deactivate, becoming fibroblasts again, or apoptose before tissue fibrosis occurs. However, when myofibroblasts persist, increased ECM protein deposition causes increased tissue stiffness and activates neighboring cells, causing the fibrosis to propagate. Currently there are no therapies to prevent or reverse fibrosis. Therefore a more thorough understanding of the dynamic mechanical environment and signaling pathways involved in the activation of fibroblasts is required to develop potential treatments.
In Vivo Three-Dimensional Morphometric Analysis of the Lumbar Spinal Bony Canal in Healthy and Low Back Pain Patients
Authors: An J. S. , Espinoza Orías A. A. , An H. S. , Andersson G. B. J. , Inoue N.
Published: July 2013

To accurately quantify the anatomic parameters of the lumbar spinal bony canal using a novel three-dimensional imaging technique based on in vivo CT three-dimensional models.
Transient Motion of Liquid Plugs With Yield Stress in Human Airways
Authors: Zamankhan Parsa , Helenbrook Brian , Takayama Shuichi , Grotberg James B.
Published: July 2013

The airway closure due to capillary instability [1] occurs in lung diseases such as asthma, cystic fibrosis, or emphysema. The reopening process involves displacement of plugs constituted from mucus, a non-Newtonian fluid with a yield stress, in the airways. In this work the transient propagation of mucus plugs in a 2D channel is studied numerically, assuming that the mucus is a Bingham fluid. The governing equations are discretized by a spectral element formulation and the free surface is resolved with an Arbitrary Lagrangian Eulerian (ALE) approach [2]. The constitutive equation for a Bingham fluid is implemented through a regularized constitutive equation. According to the numerical results, the yield stress behavior of the plug modifies the plug shape, the pattern of the streamlines and the distribution of stresses in the plug domain and along the walls in a significant way. The distribution along the walls is a major factor in studying cell injuries.
Association of Fiber Orientation and Dissection Properties of Ascending Thoracic Aortic Aneurysms With Aortic Valve Morphology
Authors: Pasta Salvatore , Phillippi Julie A. , D’Amore Antonio , Sacks Michael S. , Watkins Simon C. , Gleason Thomas G. , Vorp David A.
Published: July 2013

Type A aortic dissection (AoD) of an ascending thoracic aortic aneurysm (ATAA) is a life-threatening cardiovascular emergency with a high potential for death. Despite improved surgical techniques, the morbidity risk for emergent surgery remains 24% worldwide according to data from the International Registry of Acute Aortic Dissection [1].
Regional Mechanical Anisotropy in Decellurized Rat Heart Ventricle
Authors: Witzenburg Colleen , Raghupathy Ramesh , Kren Stefan M. , Taylor Doris A. , Barocas Victor H.
Published: July 2013

The whole cadaveric rat heart can be perfused with a detergent to completely decellurize the tissue [2]. What remains is a three-dimensional scaffold that can be repopulated with neonatal cardiac cells or rat aortic endothelial cells. However, in the development of a biological substitute to replace a tissue or organ, a critical question is how to evaluate the proposed substitute.
Physiological Micromechanics of the Anterior Mitral Valve Leaflet
Authors: Carruthers Christopher A. , Good Bryan , D’Amore Antonio , Amini Rouzbeh , Gorman Joseph H. , Sacks Michael S.
Published: July 2013

An improved understanding of mitral valve (MV) function remains an important goal for determining mechanisms underlying valve disease and for developing novel therapies. Critical to heart valve tissue homeostasis is the valvular interstitial cells (VICs), which reside in the interstitium and maintain the extracellular matrix (ECM) through both protein synthesis and enzymatic degradation [1]. There is scant experimental data on the alterations of the MV fiber network reorganization as a function of load, which is critical for implementation of computational strategies that attempt to link this meso-micro scale phenomenon. The observed large scale deformations experienced by VICs could be implicated in mechanotransduction [2], i.e., translation of mechanical stimuli into biochemical signals. Consequently, our goal is to quantitatively connect organ level loads to cellular deformation as a function of the ECM fiber network. We hypothesize that cellular deformations are likely a complex function of collagen and elastin fiber mechanical properties, architecture, and cellular coupling to these fibers.
Abrupt Recruitment of Medial Collagen Fibers in the Rabbit Carotid Artery
Authors: Hill Michael R. , Robertson Anne M.
Published: July 2013

Elastin and collagen are dominant passive load bearing proteins in the artery wall. An accepted hypothesis is that during extension of the vessel, the highly distensible elastin bears most of the load at low stretch, while increasing amounts of the less distensible medial collagen fibers uncrimp and thus bear increasing load as the overall tissue stretch increases [1]. Whether or not the collagen fibers are gradually recruited beginning at an infinitesimal stretch or at a finite stretch remains unresolved.
Multi-Laboratory Uncertainty Analysis of PIV-Measured Flow Quantities Relevant to Blood Damage in the FDA Nozzle Model
Authors: Hariharan Prasanna , Giarra Matthew , Reddy Varun , Day Steven W. , Manning Keefe B. , Deutsch Steven , Myers Matthew R. , Stewart Sandy F. C. , Burgreen Greg W. , Paterson Eric G. , Malinauskas Richard A.
Published: July 2013

Particle image velocimetry (PIV) has been used in regulatory submissions to the FDA for pre-clinical and post-market evaluations of flow fields in medical devices, such as artificial heart valves, blood pumps, and stents. The velocity and shear fields obtained from the PIV experiments are also used to validate computational fluid dynamics (CFD) data accompanying the submissions. However, previous studies have questioned the accuracy of PIV measurements in regions of high shear and low velocity (regions prone to hemolysis and thrombosis). Currently, there is no clear estimate of the amount of uncertainty involved in measuring various flow parameters in these high-risk regions. The objective of this study was to perform an inter-laboratory PIV study in a simplified nozzle model and quantify the uncertainties involved in measuring flow quantities relevant to blood damage, such as near-wall velocity, viscous and Reynolds shear stresses, size and velocity within recirculation regions, and for estimating an index of hemolysis.
Targeted Gene Silencing With Light and a Silver Nanoparticle Antisense Delivery System
Authors: Brown Paige K. , Qureshi Ammar T. , Hayes Daniel J. , Monroe W. Todd
Published: July 2013

Targeted delivery and controlled release of oligonucleotide therapeutics in vivo are essential aspects of an ideal delivery vehicle. Here we demonstrate the synthesis and in vitro/intracellular characterization of silver nanoparticle (SNP) photolabile nucleic acid conjugates, with the aim of developing a nanoparticulate platform for inducible gene silencing. Due to unique size related properties, nanostructures are being increasingly utilized for intracellular diagnostics and delivery applications. While most nanoscale delivery platforms are polymeric in composition, studies of metallic nanoparticles have highlighted their suitability for delivery of therapeutic agents such as antisense oligonucleotides [1]. The potential benefits of noble metal nanoparticles in delivery applications include tunable size and shape, ease of bulk synthesis and functionalization via ‘wet chemistry’ techniques, and enhanced stability of tethered DNA [2]. Silver is one of the best surface-enhancing substrates available for nanostructure synthesis [3]. SNP composites afford external control over surface-tethered drug release via external triggers.
In-Vitro Model of the Microscale Alveolar Environment
Authors: Higuita-Castro Natalia , Mihai Cosmin , Hansford Derek J. , Ghadiali Samir N.
Published: July 2013

The present work describes the development of a novel micro-nanoscale system that more closely resembles the alveolar-capillary barrier in the lung by recapitulating different parameters of the cellular microenvironment, including fibrous geometry, fiber stiffness, chemistry, and cell-cell interactions. The system consists of a three-dimensional multilayered structure. Two microchannel chambers that resemble alveolar/airway space and the capillary lumen, interfaced with a porous mesh of polymeric nanofibers that act as the basal substrate for seeding lung epithelial and endothelial cell. The top and bottom chambers of the device were fabricated using soft lithography techniques, while the nanofiber mesh was obtained via electrospinning. Human alveolar epithelial cells (A549) and human umbilical vein endothelial cells (HUVEC) were successfully co-cultured using this system. Various cellular and molecular biology techniques are being employed to investigate injury patterns and overall cell responses under different circumstances which mimic various lung disorders such acute lung injury, pulmonary fibrosis and emphysema.
Introduction of Contact Forces Minimization in the Musculo-Tendon Forces Optimization During Gait
Authors: Moissenet Florent , Cheze Laurence , Dumas Raphaël
Published: July 2013

Since joint contact forces can be measured using instrumented implants, they can be used to validate musculo-tendon and contact forces predicted by simulation. We propose in this study a new approach that introduces contact forces minimization in the musculo-tendon forces optimization during gait. We show that using a numerical trick, it can be possible to compute in a one-level optimization both musculo-tendon and contact forces. Moreover we show that taking into account contact forces in the optimization has a real impact on musculo-tendon forces computation.
Effect of Kinematics on the Wear Rate of the Patella Femoral Artificial Joint
Authors: Maiti Raman , Fisher John , Jin Zhongmin , Rowley Liam , Jennings Louise
Published: July 2013

Total knee replacements (TKR) have been used for the past four decades [1]. Conventional knee (tibiofemoral) wear simulators have been used to facilitate improvements in the design of TKRs [2]. This, along with surgical improvements has caused the success rate of implants to increase to 97% over a period of ten years [3, 4, and 5]. However the decision to resurface the patella still remains an issue [6, 7]. Research has been performed into the in vitro wear simulation of the patella femoral joint (PFJ) [8, 9, and 10] but to date none of these simulations have employed all six degrees of freedom (DOF).
Tenocytes, Phenotypes, Biomarkers and Functions: Roles in Bioartificial Tendons
Authors: Banes A. J. , Qi J. , Dmochowski J. M. , Tsuzaki M. , Banes A. N. , Bynum D. , Gomez S. , Wall M. E.
Published: July 2013

Tendons are designed to transmit the force of muscle contraction to bone, but they can also be positional or power structures. A sheath, where present and a surface paratenon are repositories for blood vessels and nerves. These structures penetrate inward to the epitenon, then endotenon and finally fascicle bundles. Each anatomic layer is replete with a tenocyte population distinct from the other group (Banes et al., 1998). Tenocyte surface cells (TSCs) differ from internal tenocytes (TIFs) that integrate with collagen fibrils and fascicles. TSCs are more stellate and spread, secrete fibronectin and PG4 (lubricin) and, as determined by gene array, have a different transcriptome from TIFs (Banes et al., 2004). TIFs are more spindle shaped, make collagen and are intimate with fibrils. Biomarkers for tendon are few compared to those for bone and cartilage, but recently, scleraxis (Scx), a basic helix-loop-helix transcription factor, and tenomodulin (TNMD), driven by Scx, have been identified with tendon development (Schweitzer et al., 2001). No concordance on TNMD function has been reached, but mature as well as developing TSCs and TIFs express TNMD. A TNMD KO mouse showed a mild collagen phenotype with larger, but less well organized fibrils, decreased cell proliferation, but no other problems (Docheva et al., 2005).
Oscillatory Blood Flow in a Deformable Human Aortic Arch
Authors: Wang Jing , Brown Suzie , Tullis Stephen W.
Published: July 2013

The aorta is the largest artery in humans, stemming from the left ventricle of the heart and stretching down to the abdomen. It is responsible for distributing oxygenated blood to the rest of the body during each cardiac cycle. The pulsatile blood flow is complex in nature and has been previously modeled computationally in an effort to understand its effect on cardiovascular diseases and medical device design interaction [4,8–9]. However, the majority of these models either treat the vessel wall as rigid or have significantly simplified geometries, which from a physiological perspective are not true of large vessels such as the aorta. Here, the complex mechanical interaction between pulsatile blood flow and wall dynamics in the aortic arch is investigated using geometry adopted directly from CT images.
Progressive Post-Yield Behavior of Human Cortical Bone in Shear
Authors: Dong Xuanliang Neil , Luo Qing , Giri Bijay , Wang Xiaodu
Published: July 2013

Post-yield behavior is important for bone fragility since it accounts for the major part of energy dissipation of bone. Therefore, it is essential to study the post-yield behavior of bone to understand the different pathways for energy dissipation [1]. The post-yield behavior of bone may depend on the different loading modes. Previous studies have utilized a novel progressive loading scheme to study the post-yield behavior of cortical bone at tension [2] and compression [3]. However, few studies have reported post-yield behaviors of cortical bone in shear [4]. One of major challenges in shear tests of cortical bone is to achieve a uniform stress field over a test region. For example, the notches of the Iosipescu test may cause non-constant stress fields and locally high stresses when small amounts of bending are present [5]. The objective of this study was to develop the progressive loading scheme of shear in bone using an inclined double notch shear test, in which homogeneous shear stress fields were produced [5].
The Mechanical and Structural Effects of HIV Proteins on Murine Carotid Arteries
Authors: Hansen Laura , Platt Manu , Sutliff Roy L. , Gleason Rudolph L.
Published: July 2013

Acquired immunodeficiency syndrome (AIDS) is considered a global epidemic with over 65 million people worldwide infected with the HIV-1 virus, the causative agent [1]. The development of highly active antiretroviral therapy (HAART) has significantly increased the life expectancy of people infected with the virus by slowing the progression to the development of AIDS. However, the treatment has also led to the emergence of early onset cardiovascular complications including myocardial infarction [2] and atherosclerotic lesions [3], as well as subclinical markers of atherosclerosis including increased carotid artery intima-media thickness [4], increased arterial stiffness [5–6], and endothelial dysfunction [6]. It appears that HAART and HIV-1-infection are independent risk factors for the development of atherosclerosis in adults [7]; however, the mechanism of disease progression remains unclear. There is a pressing need to identify mechanisms of early on-set cardiovascular disease associated with HIV-1 infection and HAART and to identify therapeutic strategies to reduce cardiovascular disease in HIV patients. The overall goal of this study is to test the hypothesis that over-expression of HIV proteins will lead to alterations in the biomechanical properties of large arteries.
Computational Comparison Between Normal and Bicuspid Aortic Valve Hemodynamics
Authors: Chandra Santanu , Seaman Clara , Rajamannan Nalini M. , Sucosky Philippe
Published: July 2013

The bicuspid aortic valve (BAV) is the most common congenital cardiac anomaly and is present in 2% of the population. While a normal tricuspid aortic valve (TAV) consists of three leaflets, a BAV is formed with only two as a result of the fusion of two leaflets into a larger one1. This defect is associated with serious complications such as calcific aortic valve disease (CAVD), a condition characterized by the accumulation of calcium on the leaflets which contributes to the obstruction of the left ventricular outflow and progressive heart failure. Although studies have suggested similarities in the pathogenesis of CAVD in the BAV and TAV, the calcification of the BAV is more severe and its progression more rapid. Previous studies in our laboratory have evidenced the sensitivity of valve leaflets to their hemodynamic environment and the ability of fluid stress alterations to trigger an inflammatory response on the aortic surface of porcine aortic valve leaflets2. Although a similar mechano-etiology could contribute to the rapid calcification of the BAV, it is not clear how the particular BAV anatomy impacts on its hemodynamic environment and whether the hemodynamic stresses experienced by BAV leaflets differ from those present in TAV leaflets. Therefore, the aim of this study was to characterize BAV hemodynamics and to quantify its degree of abnormality relative to a TAV. A fluid-structure interaction (FSI) approach validated with respect to particle-image velocimetry (PIV) measurements was implemented to quantify TAV and BAV hemodynamics in terms of flow velocity field, valvular effective orifice area (EOA) and leaflet wall-shear stress. The large degree of hemodynamic abnormality predicted in the BAV model may contribute to the rapid progression of CAVD in that anatomy. This work lays the foundation for future mechanobiological studies aimed at investigating the isolated effects of native BAV hemodynamic stresses on the development of CAVD.
A New Form of Residual Deformation in the Coronary Artery: Implications for In Vivo Mechanical Behavior
Authors: Wang Ruoya , Gleason Rudolph L.
Published: July 2013

Vascular residual stress has been the subject of numerous studies for more than two decades. The importance of residual stress on vascular mechanics was first recognized by Chuong and Fung [1]. They demonstrated that when circumferential residual stress was considered in the mechanical analysis, a nearly uniform stress distribution was predicted across the vessel wall. This suggested that vascular cells, despite being at different radial locations, experience the same stress environment. Residual stress is also known to exist longitudinally, and recent studies have shown that this highly effects the stress environment as well [2]. This study presents a new form of vascular residual stress, one that occurs in shear, within the porcine coronary artery. The effects of residual shear stress on the transmural stress profile are examined. We hope the results can lead to a better understanding of the residual stress field, and therefore help develop more robust and predictive models for vascular diseases.
Size Ratio of Intracranial Aneurysms Predicts Rupture-Prone Hemodynamics
Authors: Xiang Jianping , Siddiqui Adnan , Natarajan Sabareesh K. , Meng Hui
Published: July 2013

Hemodynamics plays an important role in IA pathophysiology and rupture.1, 2 Since flow dynamics is largely determined by geometry,3 IA hemodynamics has been thought to be dependent on the aneurysm and/or parent vessel morphology.
Nano-Mechanical Properties of Bioceramic Bone Scaffolds Fabricated at Three Sintering Temperatures
Authors: Vivanco Juan , Slane Josh , Ploeg Heidi
Published: July 2013

Bone grafting is an exceptionally common procedure used to repair bone defects within orthopaedics, craniofacial surgery and dentistry. It is estimated that 2.2 million grafting procedures are performed annually worldwide [1] and maintain a market share of $7 billion in the United States alone [2]. There has been a considerable rise in the interest of using bioactive ceramic materials, such as hydroxyapatite and tricalcium phosphate (TCP), to serve as synthetic replacements for autogenous bone grafts, which suffer from donor site morbidity and limited supply [3]. These ceramic materials (which can be formed into three-dimensional scaffolds) are advantageous due to their inherent biocompatibility, osteoconductivy, osteogenecity and osteointegrity [2].
Compression Force Measurement During Cell Spreading Using a Modified Atomic Force Microscope
Authors: Weafer Paul , van Es Maarten H. , Jarvis Suzanne P. , McGarry Patrick J.
Published: July 2013

Mechanical forces play a critical role in the regulation of cell spreading and cytoskeletal organization. It has been demonstrated that the force required to compress a spread cell is significantly higher than that required to compress a cell with a rounded morphology [1]. This increase in force can not be attributed to morphological changes alone [2], highlighting the importance of cytoskeletal remodeling during cell spreading in the resistance of cells to compressive forces.
Experimental Study of Powered Fontan Hemodynamics in an Idealized Total Cavopulmonary Connection Model
Authors: Kennington Jeffrey R. , Rodefeld Mark D. , Frankel Steven H. , Chen Jun , Kerlo Anna-Elodie M. , Giridharan Guruprasad A. , Koenig Steven C. , Sobieski Michael A.
Published: July 2013

Cardiac single ventricle birth defects are a leading cause of death among birth defects for children under one years of age. Fontan palliation is the current clinical treatment for patients with these birth defects and result in a single working ventricle to power the entire system by forming a total cavopulmonary connection (TCPC). A significant number of patients with univentricle Fontan circulation develop Fontan failure caused by the inability of the single ventricle to power the Fontan circulation. The use of mechanical cavopulmonary assist device has been proposed as a treatment for these patients. Particularly, the application of a percutaneous, catheter driven, viscous impeller pump (VIP) has been identified to provide promising cavopulmonary support [1]. Computational Fluid Dynamics (CFD) simulations have demonstrated that this VIP pump can satisfactorily augment cavopulmonary blood flow at pressures sufficient to overcome increased downstream resistance. Experimental characterization of flow induced by the VIP in the TCPC, including detailed flow structures and hemodynamic performances, needs to be conducted for minimizing risk of hemolysis and thrombosis while maximizing the pump performance, and for validating the results from high-fidelity CFD simulations.
The Mechanical and Biochemical Environment Controls Cellular Differentiation During Muscle Regeneration
Authors: Calve Sarah , Simon Hans-Georg
Published: July 2013

Urodele amphibians like the newt, are able to completely regenerate lost organs and appendages without scarring. Differentiated tissues are considered a reservoir for uncommitted blastema cells that participate in the regeneration of the lost structure. To determine the influence of the extracellular matrix (ECM) on the recruitment of progenitor cells from the skeletal muscle, we immunohistochemically mapped the limb in 3D and found that a transitional ECM rich in hyaluronic acid (HA), tenascin-C (TN) and fibronectin (FN) is dynamically expressed during the early stages of regeneration [1]. Functional in vitro testing of different ECM components on primary muscle cells revealed that HA and TN support myoblast migration, inhibit differentiation and enhance the fragmentation of multinucleate myotubes and production of viable mononucleate myoblasts, cellular behaviors necessary for blastema formation [1]. In contrast, myoblasts plated on matrices that mimic ECM around differentiated muscle (FN, Matrigel and laminin) induced both proliferation and fusion.