bluuebunny/crossref_metadata_2025 huggingface dataset:
A 3-D Constrained Mixture Model for Vascular Growth and Remodeling
Authors: Wan William , Hansen Laura , Gleason Rudolph L.
Published: July 2013

It is known that arteries adapt and remodel to changes in their loading conditions. Evolution of mechanical properties of blood vessels is associated with numerous chronic and acute conditions such as hypertension and coronary thrombosis. In addition, treatments such as bypass surgery create loading conditions not seen in normal arteries. Blood vessels used in coronary bypass grafts experience abnormal loading conditions in both circumferential and axial directions. Blood vessels remodel by altering structural components to restore homeostatic values of stress. Such changes may include smooth muscle cell proliferation, migration and collagen synthesis, degradation, and remodeling. While biaxial mechanical tests and organ culture experiments provide values for global variables such as mean stresses and total thickness, mathematical models can help describe local mechanical properties at locations throughout the vessel wall. Experimental observations suggest that constituents of arteries turnover at different rates; thus, it is important that models are able to track individual constituents of the artery separately. Here, we present a 3D constrained mixture model for growth and remodeling of arteries exposed to large changes in flow, pressure, and axial stretch -induced.
Extracellular Matrix Stiffness Modulates Microvascular Morphology During Early Sprouting Angiogenesis In Vitro
Authors: Krishnan Laxminarayanan , Utzinger Urs , Maas Steve , Reese Shawn , Weiss Jeffrey A. , Williams Stuart K. , Hoying James B.
Published: July 2013

Sprouting angiogenesis is associated with changes in matrix stiffness[1]. Neovessel growth and morphology are in turn affected by the changes in matrix orientation or forces acting on the matrix[2]. Matrix rigidity influences the formation of cord like structures[3, 4] and could play a role in development of tissue specific vascular morphology or inhibit cellular functions in diseases. The effect of matrix stiffness on neovessel growth from preformed vasculature has not been examined. Matrix stiffness could be increased both by an increase in matrix density[5] as well as increased crosslink formation, as in hyperglycemia[6]. It is thus essential to first identify the effect of increase in local stiffness alone, in the absence of artificially induced crosslinks, which may interfere with matrix orientation. Our aim is to characterize changes in early angiogenesis associated with ECM of different densities and relate these to changes in matrix orientation.
Carbon Nanotube Peapod-Mediated Laser Cancer Therapy
Authors: Whitney Jon , Zhang Jianfe , Dorn Harry , Campbell Tom , Naha Sayan , Rylander Marissa Nichole
Published: July 2013

Development of dual diagnostic and therapeutic agents for cancer with heightened sensitivity, selectivity, and lower toxicity could greatly enhance the prognosis of patients suffering from this disease. Recent work by Dr. Harry Dorn of Virginia Tech has resulted in the creation of a novel nanostructure called a carbon nanotube peapod. This structure consists of multiple TNT EMF’s (Trimetallic nitride template endohedral metallofullerenes) contained within a single-walled carbon nanotube (CNT) in the form of a peapod. Using TNT EMFs containing gadolinium, this nanostructure can achieve a 40-fold improvement in magnetic resonance imaging (MRI) contrast enhancement [1]. The CNT component of the peapod can be utilized as a hyperthermia enhancer [2] and an effective platform for drug delivery [3]. This study focuses on the use of carbon nanotube peapods (CNT peapods) to absorb near infrared light and generate therapeutic heat for tumor destruction. With sufficient heating and nanoparticle targeted delivery to tumor cells, CNT peapods can potentially induce selective hyperthermia-mediated toxicity in tumors.
Dielectrophoretic Microweaving: Biofabrication of Aligned Bacterial Nanocellulose for Regenerative Medicine
Authors: Sano Michael B. , Davalos Rafael V. , Gatenholm Paul
Published: July 2013

The use of natural and synthetic polymers as scaffolding material for regenerative medicine is far from clinical translation for most tissue applications. This is due primarily to lack of manufacturing control over mechanical properties and 3D architecture which promote cell attachment and proliferation. Cellulose, a natural polymer produced by the majority of plants, can be assembled into nanofibrils by bacteria. The advantage of bacterial cellulose is that it has unique biocompatibility, mechanical integrity, hydroexpansivity, and is stable under a wide range of conditions [1]. It is thus ideal as a scaffolding material on which to seed cells for regenerative medicine applications. The bacteria Acetobacter Xylinum produces nanoscale cellulose ribbons at an average rate of 2μm/min [2].
Tissue Engineered and Native Ovine Pulmonary Valves: A High Resolution Three-Dimensional Structural Characterization
Authors: Eckert Chad E. , Mikulis Brandon T. , Gerneke Dane , LeGrice Ian , Gottlieb Danielle , Mayer John E. , Sacks Michael S.
Published: July 2013

Tissue engineered heart valves (TEHV) have received much attention as a potential pediatric valve replacement therapy, offering a variety of prospective long-term functional improvements over current options. Early in vivo and in vitro efforts have produced TEHV showing increasingly equivalent mechanical and structural properties compared to native valves [1]. Despite these advances, a significant gap in the literature exists regarding detailed 3D structural information of TEHV prior to implantation (in vitro) and after implantation (explants) as well as that of the native valve. The present work was performed to provide high resolution 3D structural data of implanted TEHV, the native pulmonary valve (PV), and pre-implant scaffold to develop an accurate understanding of developing tissue.
Quantification of Elastin Residual Stretch in Fresh Artery Tissue: Impact on Artery Material Properties and Pulmonary Hypertension Pathophysiology
Authors: Lammers Steven R. , Kao Phil H. , Tian Lian , Hunter Kendall , Qi H. Jerry , Albietz Joseph , Hofmeister Stephen , Stenmark Kurt , Shandas Robin
Published: July 2013

Pulmonary arterial hypertension (PAH) is characterized as a chronic elevation in mean pulmonary artery pressure (MPAP) resulting from increased hydrodynamic resistance and decreased hydraulic capacitance of the pulmonary circulatory system. These hemodynamic changes cause the heart to operate outside optimum pump efficiency. The heart compensates for the efficiency loss through ventricular hypertrophy which, if left untreated, will continue until cardiac failure results.
A Novel Method for Excluding Aneurysms From the Cerebral Circulation: Preliminary Results in Rabbits
Authors: Lieber Baruch B. , Sultan Mohammad Ali-Aziz , Sadasivan Chander , Watson Brant D. , Cesar Liliana , Wolfe Stacey Quintero , Trager Asher L. , Farhat Hamad , Moftakhar Roham , Elhammady Mohamed Samy
Published: July 2013

Despite many advances in the treatment of cerebral aneurysms in the last few decades, none of the available methods provide an unequivocal solution for all aneurysm sizes and morphologies. The feasibility of successfully treating aneurysms solely by the placement of an intravascular flow-diverting mesh across the aneurysm neck was established more than a decade ago [1]. Flow diverters disrupt the momentum exchange between the parent artery and aneurysm and significantly reduce intraaneurysmal hydrodynamic vorticity and kinetic energy. The resultant flow stasis promotes thrombus formation within the aneurysm sac, which eventually matures into fibrotic tissue, leading to exclusion of the aneurysm from the circulation. With the increased use of stents in the intracranial circulation, cases where coiling is not feasible, or is staged as a secondary procedure, are providing clinical evidence of the successful treatment of aneurysms with stents alone [2,3]. Methodological evidence of the performance of appropriately designed flow diverters in treating cerebral aneurysms has recently become available in the literature [4,5].
Scleral Biomechanics in the Glaucomatous Monkey Eye
Authors: Girard Michaël J. A. , Suh Jun-Kyo F. , Bottlang Michael , Burgoyne Claude F. , Downs J. Crawford
Published: July 2013

The sclera is the outer shell and principal load-bearing tissue of the eye, and consists primarily of avascular lamellae of collagen fibers. Ninety percent of the collagen fibers in the sclera are Type I, which provide the eye with necessary mechanical strength to withstand intraocular pressure (IOP). A small hole pierces the posterior sclera, known as the scleral canal, through which the retinal ganglion cell axons turn and pass out of the eye on their path to the brain. The scleral canal is spanned by a fenestrated connective tissue called the lamina cribrosa that provides structural and nutritional support to the axons as they leave the eye. This region, including the peripapillary sclera (the sclera closest to the canal), the lamina cribrosa, and the contained retinal ganglion cell axons, is collectively known as the optic nerve head or ONH.
Regional Similarities in the Mechanical Properties of the Human Umbilical Artery
Authors: Martin John T. , Ferguson Virginia L.
Published: July 2013

The human umbilical cord (UC) bridges the blood flow gap between baby and mother, protecting the blood supply in a way that allows the fetus freedom to move within the amniotic sac. Once the blood supply has been oxygenated by the maternal blood pool via the placenta, the umbilical vein (UV) provides a transport pathway to the fetus. Two umbilical arteries (UA) return the blood supply to the pool to eliminate CO2 and other metabolic wastes [1]. The walls of the UA’s and UV are made up of an intima composed a single layer of large, elongated endothelial cells [2], and a media composed of randomly distributed smooth muscles cells, collagen, elastin, and ground substance. These vessels are unique in that their adventitia is absent and substituted by Wharton’s jelly, a mucoid connective tissue.
Quantitative Validation of a Finite Element Model of a Knee-Thigh-Hip Complex of a 50th Percentile Male
Authors: Mongiardini Mario , Silvestri Chiara , Ray Malcolm H.
Published: July 2013

Traditionally the validation process of FE models is carried on by visually comparing two curves, respectively from an experimental test and the numerical simulation. A more rigorous way to quantitative compare two curves in the validation process would be provided by comparison metrics.

In this work the component validation of the Finite Element model of a Knee-Thigh-Hip complex was carried on by quantitatively comparing the results from the experimental tests with the corresponding numerical curves. An LSDYNA finite element model of the lower extremities was developed and the condyle, pelvis and femur and components were carefully validated using three comparison metrics. The good match.
Mesenchymal Stem Cell Seeded Nanofibrous Laminates Mimic the Multi-Scale Form and Function of the Annulus Fibrosus
Authors: Nerurkar Nandan K. , Sen Sounok , Wible Emily E. , Stambough Jeffrey B. , Elliott Dawn M. , Mauck Robert L.
Published: July 2013

The annulus fibrosus (AF) of the intervertebral disc is a multi-lamellar fibrocartilage that, together with the nucleus pulposus, confers mechanical support and flexibility to the spine. Function of the AF is predicated on a high degree of structural organization over multiple length scales: aligned collagen fibers reside within each lamella, and the direction of alignment alternates between adjacent lamellae from +30° to −30° with respect to the transverse axis of the spine. Electrospinning permits fabrication of scaffolds consisting of aligned arrays of nanofibers, and has proven effective for directing the alignment of both cells and extracellular matrix (ECM) deposition [1–3]. We recently employed electrospinning to engineer the primary functional unit of the AF, a single lamella [4]. However, it remains a challenge to engineer a multi-lamellar tissue that replicates the cross-ply fiber architecture of the native AF. Moreover, relatively few studies have considered functional properties of engineered AF, and, when measured, tensile properties of these constructs have been inferior to native AF [4]. In this study, mesenchymal stem cells (MSCs) were seeded onto aligned nanofibrous scaffolds organized into bi-lamellar constructs with opposing or parallel fiber orientations, and their functional maturation was evaluated with time. Additionally, we determined a novel role for inter-lamellar ECM in reinforcing the tensile response of bilayers, and confirmed this mechanism by testing acellular bilayers with controllable interface properties.
Age-Related Changes in Structure, Composition and Mechanical Properties of Swine Cortical Bone
Authors: Feng Liang , Bhargava Rohit , Jasiuk Iwona
Published: July 2013

Bone has a complex hierarchical structure spanning from nanometer to macroscopic dimensions. We apply several experimental methods at different structural scales to study the three fundamental aspects of this material: the structure, composition and mechanical properties. As a biological material, bone is constantly under development. These biological processes such as remodeling and aging are known to increase the susceptibility of bone to fracture. The age-related changes in the fracture toughness and other mechanical properties are manifested by the alteration of the bone structure and chemical composition [1]. Various studies addressed the changes in bone’s structure, composition and mechanical properties due to aging [2–5]. However, these studies were confined to only one or two of these aspects, separately. So there is still an open question about how these three aspects are correlated with each others. Thus, a comprehensive study is needed to address it.
Automated Measurement of Callus Formation
Authors: Lujan Trevor J. , Henderson Chris E. , O’Donovan Meghan , Madey Steve M. , Fitzpatrick Dan C. , Bottlang Michael
Published: July 2013

The assessment of fracture healing is aided by identifying features in roentgenographs that signify bone union. In comminuted or multi-part fractures, external callus formation relates to mechanical rigidity at the fracture site.[1] However, inter- and intra-observer variability of 20–25% exists when physicians evaluate callus.[2] Furthermore, current classification systems lose information by converting continuous features into categorical variables.[3] These limitations have restricted the clinical utility of plain radiographs in retrospective evaluation of treatment course.[4,5] Image processing presents a viable means to reduce observer error, while yielding continuous results. The aim of this work was to verify, numerically and clinically, an objective method to quantify callus formation.
Patient Specific FEM Analysis of the Atherosclerotic Carotid Bifurcation
Authors: Leach Joseph R. , Rayz Vitaliy L. , Mofrad Mohammad R. K. , Wintermark Max , Saloner David
Published: July 2013

Atherosclerosis in the carotid bifurcation is a highly variable disease that, in its stable form, can cause a dangerous reduction of blood flow to the brain. If the plaque ruptures or ulcerates, the patient is likely to experience a thrombotic or embolic stroke. Stroke is the 3rd leading cause of death in the western world, and approximately 10–15% of these cases develop from carotid atherosclerosis [1]. In addition to the complex biochemistry involved in the initiation, progression, and acute insult of carotid disease, the mechanical environment of the carotid bifurcation may also play a pivotal role in these disease states.
Lumbar Spinal Mechanics in Pure Bending: Influence of Gender, Spinal Level, and Degeneration Grade
Authors: Stemper Brian D. , Barnes David , Baisden Jamie L. , Yoganandan Narayan , Pintar Frank A. , Moore Jason , Maiman Dennis J.
Published: July 2013

Gender differences have been identified in normal and traumatic motions of the spine. In the cervical region, spinal motions in females were significantly greater than in males during identical dynamic acceleration pulses [1]. Static cervical range of motion was also shown to be greater in female volunteers [2]. In the thoracic region, gender differences were identified in compressive and tensile elastic moduli [3]. Although male volunteers had slightly greater lumbar spine mobility, the difference was not statistically significant [4]. Another study reported that female lumbar specimens were somewhat more flexible than male specimens [5]. Lumbar spinal motions are clinically important in the diagnosis of abnormalities and instability. Increased motions occur secondary to instability and may indicate a need for spinal stabilization. However, although previous studies have provided baseline data for lumbar motions [6], possible variations in spinal motions between males and females may lead to inaccurate diagnosis. Therefore, the purpose of this investigation was to define lumbar spinal motions on a level-by-level basis to determine statistically significant differences between males and females and at varying levels of degeneration.
Assessment of Local Bone Mineral Density With Strain-Gage Instrumented Surgical Tools
Authors: Marmor Meir , Fong Marshall , Chu Thomas , Han Hyun Kyu , Tai Viva , Matityahu Amir , Buckley Jenni M.
Published: July 2013

The bone mineral density (BMD) in a given fracture site may affect the outcome of fracture fixation. Low BMD values, such as those occurring in osteoporotic bone, can determine the fixation method and the postoperative care. Evaluation of the BMD is either done subjectively during surgery or by a preoperative measurement. The technique most commonly used to measure BMD preoperatively is dual-energy X-ray absorptiometry (DEXA). DEXA scans have been shown to be site specific [1,2] and therefore may be inaccurate in determining local BMD at the fixation site. Furthermore, in trauma cases, patients frequently do not present with a pre-operative DEXA scan; and the ideal method of assessment would be intraoperative. Intraoperative BMD assessment could be used to guide surgical decisions such as the point of entry of a screw for a fracture plating system or use of locking versus non-locking screw-plate contruct.
Annulus Fibrosus Shear Properties Are Consistent With Motion Segment Mechanics When Fibers Are Loaded
Authors: Yoder Jonathon H. , Henninger Heath B. , Weiss Jeffrey A. , Elliott Dawn M.
Published: July 2013

The annulus fibrosus (AF) is a highly organized structure made up of concentric lamellae of fibers embedded in a hydrated extrafibrillar matrix; the collagen fibers are oriented at alternating angles in each lamella. The AF undergoes multidirectional loading through combinations of compression, bending, torsion and shear of the motion segment. The composition and structure of the AF leads to mechanical stress-strain nonlinearity and anisotropy. Previous tissue-based studies of shear have tested the AF tissue under compressive simple shear and torsion, producing shear modulus on the order of 0.06–0.4 MPa [1, 2]. However, structural testing and mathematical models of the IVD have reported the shear modulus to be between 3–20 MPa [3–6]. We hypothesize that when the fibers of the AF are loaded the shear modulus will be on the same order as structural tests and mathematical models of the IVD. The objectives of this study are to measure the shear mechanical properties of the bovine outer AF and compare the regional variances between anterior and posterior AF.
A Longitudinal Study of Migration Forces on a Patient-Specific Abdominal Aortic Endograft Model
Authors: Yeh Victoria , Chiou Allen , Taylor Charles A. , Zarins Christopher K. , Figueroa C. Alberto
Published: July 2013

Aortic endografts are a popular alternative to open surgery as a treatment for abdominal aortic aneurysms (AAA) [1]. However, device migration often occurs if the endograft is inadequately fixed. This is due, among other factors, to the time-varying loads exerted by pulsatile flow and pressure in the aorta. Improper fixation may lead to adverse clinical events such as endoleaks and ruptures.
Development of Physics-Based Model and Experimental Validation of Helmet Performance in Blast Wave TBI
Authors: Przekwas Andrzej , Chancey V. C. , Tan X. G. , Chen Z. J. , Wilkerson P. , Zhou A. , Harrand V. , Imielinska C. , Reeves D.
Published: July 2013

Explosive devices are the main weapon of terrorist attacks and a cause of major injuries to Soldiers and civilians. Recent military medical statistics show that a significant percentage of Soldiers injured in explosion events endures blast wave traumatic brain injury (BW-TBI). In the last few years, better understandings of BW-TBI mechanisms and of improved injury protection have become of paramount importance. Most studies have taken the conventional approach of animal testing, in vitro brain tissue study, and analysis of clinical data. These, while useful and necessary, are slow, expensive, and often non-conclusive. Physiology-based mathematical modeling tools of blast wave brain injury will provide a complementary capability to study both BW-TBI mechanisms and the effectiveness of protective armor.
Fluid Stress Analysis During Airway Closure
Authors: Tai Cheng-Feng , Halpern David , Grotberg James B.
Published: July 2013

A thin annular film lining the inside of a rigid tube is modeled as a liquid-lined airway in this study. Due to the capillary instability, the liquid film can form a plug and obstruct the airway once the ratio of the film thickness to tube radius, ε, is greater than a critical value ∼0.12. The dynamics of the closure process is simulated for a Newtonian viscous film with constant surface tension and a passive core gas phase. The numerical simulation employs the finite volume approach with a sharp interface method for the free surface. The computational results show that the wall shear stress and normal stress during closure can be strong enough to injure airway epithelial cells.
Recellularization Potential of Acellular Aortic Valve Scaffolds Treated With Collagenase and Acetic Acid
Authors: Weed Benjamin C. , Borazjani Ali , Metzler Scott , To Filip , Warnock James , Liao Jun
Published: July 2013

It is estimated that five million Americans suffer from moderate to severe aortic valve disease, making it the third most common type of cardiovascular disease. Aortic valve replacement, which is second leading reason for undergoing open heart surgery, is the prevailing treatment for patients with extensive aortic valve pathologies. Currently, substitute valves used to replace the disease valves are classified as either mechanical or biological, each of which carry significant disadvantages. Patients with mechanical valves are at a much higher risk for developing blood clots and therefore must remain on anticoagulants for the remainder of their lifetime; and biological valves, which are typically derived from porcine or cadeveric tissues, will deteriorate over time. The ideal replacement valve is one that presents no thrombogenicity or immunogenecity, provides normal hemodynamics, is free of blood damaging elements, offers a practical mode for implantation, is able to grow and remodel, and does not deteriorate over time.
High-Resolution Arterial Pressure-Area Loops in Rats
Authors: Fancourt Craig , Su Yuzhuo , Sachs Jeffrey R. , Bunzel Michelle , Campbell Barry R. , Walker Matthew , Azer Karim
Published: July 2013

The artery wall is compliant and stretches in response to the traveling pressure pulse generated by the contracting heart. The dynamics of this motion are known to convey important information about the health of the artery and cardio-vascular system. For example, compliance, a measure of artery flexibility, decreases due to aging, as well as disease states such as hypertension and atherosclerosis. It also exhibits acute and chronic changes under pharmacological interventions.
Quantifying Complexity and Variability of Gait Phase Portraits
Authors: DiBerardino Louis A. , Polk John D. , Rosengren Karl S. , Hsiao-Wecksler Elizabeth T.
Published: July 2013

Injuries to the lower extremity can limit joint motion and alter movement patterns of the limb segments during gait. Researchers have also found changes in variability and complexity as a function of injury. Injury or joint pain appears to decrease gait cycle variability [1]; however, the results on complexity are less clear. While some researchers have found a decrease in complexity due to disease and aging, e.g., [2], others have found an increase in complexity [3]. One of the goals of the current work was to quantify changes in the variability and complexity of motion patterns as assessed using phase portraits.
Development of a Finite Element Model Framework for Studying Growth of Cartilage Anlage
Authors: Mahmoodian Roza , Siegler Sorin , Capaldi Franco
Published: July 2013

Growth and remodeling are fundamental processes in the development of tissues in normal and pathological conditions. Mechanical quantities such as stress, strain or strain energy in the tissue can modulate its growth and remodeling; however, it is not clear yet which mechanical quantity takes this role. Experimental data can be found to support both. Furthermore, the driving-mechanism may be tissue-dependent and therefore, a universal growth law may not exist [7,8]. This field has been an important research topic in biomechanics over the recent decades. The review articles by Humphrey [4] and Taber [8] contain numerous related references. An important contribution was made by Rodriguez et al. [7] to the area of volumetric growth of soft elastic tissue which allowed for the coupling between stress and finite growth through multiplicative decomposition of the deformation gradient into elastic and growth parts. This theory has been followed in our study. Our goal is to model growth of the hind foot cartilage anlagen in newborn infants, and explore effect of congenital anomalies on the otherwise normal development.
MEMS-Based Microballoons Achieving Multidirectional Large-Strain for Cell Mechanics Studies
Authors: Yoon Sang-Hee , Reyes-Ortiz Vimalier , Mofrad Mohammad R. K.
Published: July 2013

The influence of mechanical stresses on cells has been a topic of special interest [1]. Attention is being focused on the cell-to-cell and cell-to-surrounding interactions and the mechanical stimuli that could be directly linked with functional adaption and pathological conditions of each cell or cluster of cells [2]. The aim of this research is to understand the biomechanical roles of cellular junctions on epithelial cells, exposed to a large multidirectional and uniform strain, using a microballoon (MB) platform. Quantitative measurement on strain values can be used to determine the necessary strains at which intercellular and cell-to-substrate connections are disassembled. This will provide information for characterizing cell-to-cell and cell-to-substrate adhesions during biological development and/or diseases.
Cytoskeletal Control of Mesenchymal Stem Cell Nuclear Deformation on Nanofibrous Scaffolds
Authors: Nathan Ashwin S. , Baker Brendon M. , Mauck Robert L.
Published: July 2013

Nanofibrous scaffolds hold great potential for tissue engineering as they recapitulate the mechanical and topographic features of fibrous tissues on both the macroscopic and microscopic level [1,2]. When seeded with cells capable of fibrous extracellular matrix (ECM) production such as mesenchymal stem cells (MSCs), the new matrix is deposited in accordance with the underlying topography, and scaffolds develop improved mechanical properties with time in free swelling culture [6]. While promising, the free swelling conditions employed in evaluating in vitro construct maturation have thus far remained insufficient in achieving native-level properties. As most fibrous tissues are subjected to loading in vivo, mechanical conditioning is considered critical in directing tissue development and subsequent homeostasis with normal use. Mechanical signals are translated from the ECM to the nucleus via the cytoskeleton, with signals culminating in the control of biosynthetic activity based upon external loading conditions. Various bioreactor systems have been developed to mimic these in vivo conditions towards enhancing the maturation of engineered constructs, with most focusing on dynamic tensile deformation [3,4]. Towards gaining further insight into the means by which mechanical cues inspire alterations in cellular behavior, this study developed methods for evaluating cell and sub-cellular deformation of MSCs seeded on randomly-oriented and aligned nanofibrous scaffolds. Using a device that enables visualization of cells seeded on nanofibrous scaffolds undergoing static tensile deformation, we examined the effect of applied strain rate on cell adhesion to scaffolds, as well as changes in nuclear shape in the context of viable actin and microtubule sub-cellular networks with applied strain. These data provide new insight into fundamental mechanisms of MSC mechanoregulation on nanofibrous scaffolds, and offer constraints for long-term bioreactor studies.
Removal of Sacrificial Fibers Enhances Long Term Cell and Matrix Distribution in Aligned Nanofibrous Scaffolds
Authors: Baker Brendon M. , Montero Giana , Mauck Robert L.
Published: July 2013

Given their ability to dictate initial cell alignment and subsequent matrix organization, aligned electrospun scaffolds are a fitting means for engineering fiber-reinforced, anisotropic tissues such as tendon, ligament, the knee meniscus, and the annulus fibrosus [1–3]. However, one commonly observed limitation of such scaffolds is the relatively slow infiltration rates of surface-seeded cells, where the central thicknesses of constructs cultured for 10 weeks remain devoid of cells [2]. This limitation arises from the tight packing of fibers which yields small pore sizes, thereby hampering cell migration. Towards accelerating cell ingress, we have recently reported on two-polymer composite scaffolds containing both slow eroding poly(ε-caprolactone) (PCL) fibers as well as water-soluble poly(ethylene oxide) (PEO) fibers that serve as space holders during scaffold formation [4]. Removal of these PEO fibers prior to seeding resulted in improved cell infiltration after 3 weeks, but the long term maturation of such constructs has yet to be characterized. To assess the effect of sacrificial PEO fiber content on construct growth, a triple-jet electrospinning device was employed to generate PCL/PEO scaffolds with PEO fiber fractions ranging from 0 to 60%. After seeding with mesenchymal stem cells (MSCs), constructs were clamped in custom grips to maintain strip morphology. The mechanical and biochemical maturation of constructs was assessed over 9 weeks of free swelling culture in a chemically defined medium (CDM), along with cell infiltration and matrix distribution. We hypothesized that enhanced pore size in dual-fiber constructs would lead to not only a better distribution of cells, but also larger increases in stiffness resulting from enhanced matrix production and distribution.
Improved Patient-Specific Coronary Artery Graft Configurations Using CFD Coupled Shape Optimizer
Authors: Dur Onur , Coskun Sinan T. , Kara Levent B. , Pekkan Kerem
Published: July 2013

Bypass conduits provide an alternative route around critically blocked arteries. Current surgical anastomosis techniques and the design of synthetic coronary artery bypass grafts (CABG) frequently lead to post-surgical complications such as intimal thickening, restenosis and eventual long term graft failure. Pathological hemodynamic states are usually precursors of intimal hyperplasia or platelet deposition and result in graft occlusion. From fluid mechanics perspective, abnormalities in coronary flow include recirculation zones, low/oscillating shear stresses, vortices, and areas of stagnation within the CABG.
Geometric Enhancements of an Arteriovenous Graft
Authors: Broderick Stephen P. , Carroll Gráinne , Walsh Micheal
Published: July 2013

End Stage Renal Disease (ESRD) is the degeneration of kidney function to remove uremic toxins from the blood. Currently there are over 484,000 sufferers of ESRD in the United States, with this figure predicted to rise to over 800,000 by 2020 [1]. The total cost of care for patients with ESRD was estimated to exceed 1 billion dollars in the United States [2]. A kidney transplant is the ideal solution for ESRD patients; however with the increasing number of ESRD patients the odds of receiving a donor kidney are poor. The alternative is hemodialysis. This process is involves the extraction of blood from the patient to an extracorporal machine. Blood is pumped at a rate of 350 mL/min to ensure effective dialysis. The blood is then returned to the body cleaned. The gold standard for hemodialysis access is the native arteriovenous fistula [3] with the most common type being the Brescia-Cimino fistula at the wrist [4]. In some subgroups the fistula performs poorly. In diabetics and the elderly, specifically over 70s [2] or can’t be constructed because of unsuitable blood vessels [5]. In this case an alternative is the synthetic AV graft. Made of polytetrafluoroethelyne, it has lower patency rates against the fistula [6] [7] mediated by the susceptibility to thrombosis induced by stenosis development and infection [7].The majority of stenosis development is within the venous anastomosis (kanterman1995). The formation of intimal hyperplasia (IH) leading to stenosis formation is caused by smooth cell proliferation and migration as a result of endothelial cells reacting to shear stress receptors. The development of IH has been linked to local hemodynamics and turbulence in the flow, which in turn are heavily influenced by the geometry of the graft.
Tension Induces Changes in Lipid Lateral Diffusion in Model Fluid-Phase Membranes
Authors: Muddana Hari S. , Gullapalli Ramachandra R. , Butler Peter J.
Published: July 2013

Shear stress due to blood flow on endothelial cells elicits numerous responses including G-protein coupled receptor activation and integrin-mediated signaling. Shear-induced change in membrane fluidity has been suggested to be one of the earliest mechanosensing mechanism involved in these processes [1, 2]. Alternatively, it has been suggested that shear forces are transduced through glycocalyx directly to transmembrane proteins and cytoskeleton [3], with very little shear force sensed by the membrane. It is not yet clear whether physiological tensions can alter membrane fluidity significantly.
Measuring Skeletal Kinematics With Accelerometers on the Skin Surface
Authors: Ayer K. , Lopez M. , Murphy M. C.
Published: July 2013

Gait analysis is an area within biomechanics that quantifies the motion of an animal. The most common motion analysis method uses cameras to track the position of markers on bodily surfaces over time. Although each species has a common skeletal frame to reference recorded motions, the soft tissue covering each is not rigid. Markers, therefore, experience motion relative to the bone and do not accurately portray underlying bone activity. This limits clinical use of motion studies and the understanding of joint motion.
Non-Invasive Bone Deformation Measurements Using a Pulsed-Phase-Locked-Loop Technique
Authors: Serra-Hsu Frederick , Qin Yi-Xian
Published: July 2013

Ultrasound has been widely used to non-destructively evaluate many kinds of materials, from metals to ceramics with more recent applications in bone tissues. Due to the adaptability of living bone to its mechanical environment both exercise and disease can have a profound effect on bone properties, and its ability to perform its necessary functions. Osteoporosis has become increasingly important as its manifestations are felt throughout the healthcare system. Osteoporosis is responsible for over 1.5 million fractures annually [1], which in turn cause disability and other health problems and increased mortality. The population affected is ever growing, and currently includes over 10 million Americans, with 34 million more at immediate risk (with osteopenia). [1] Recently, Quantitative Ultrasound (QUS) has begun to be used to assess bone quality and fracture risk; providing a more informative and safer technique than DEXA for osteoporosis diagnosis. [2] QUS provides useful information about bone structure; however currently remains mainly a correlative method for quality and fracture risk prediction.
Steady State Creeping Displacement of a Semi-Infinite Gas Bubble in a 2D Channel Filled by a Bingham Liquid
Authors: Zamankhan Parsa , Takayama Shuichi , Grotberg James B.
Published: July 2013

The mucus layer which covers the respiratory tract is a non-Newtonian fluid with a yield stress. The amount of shear stress must exceed a certain value before significant deformation (i.e. flow) can occur. Therefore, for better understanding of some interesting phenomena in the airways, such as the propagation or rupture of a mucus plug, as may occur in asthma, cystic fibrosis, or emphysema, the yield stress behavior of the fluid needs to be considered as well.
Synthesis, Cellular Uptake, and Cytotoxicity of a Thermally Responsive Nanocapsule
Authors: Zhang Wujie , Rong Jianhua , Wang Qian , He Xiaoming
Published: July 2013

Recently, polymeric nanoparticles have attracted tremendous interests as a useful tool to encapsulate therapeutic drugs, genes, and proteins for their controlled and sustained delivery. Among them, polymeric hydrogel nanoparticles with thermal and/or pH responsiveness have attracted particular attention [1]. Trehalose, a non-reducing disaccharide of glucose, has been demonstrated to be a potent, nontoxic bioprotectant for stabilizing lipids, proteins, viruses, and blood cells at cryogenic and particularly, ambient temperatures (i.e., cryo and lyopreservation) [2]. However, intracellular delivery of trehalose into small eukaryotic mammalian cells in a large quantity for biostabilization purpose has not been very successful so far [2]. In this study, a thermally responsive polymeric nanocapsule was synthesized and characterized with the aim to encapsulate trehalose for its intracellular delivery.
Angiogenic Nanoscaffold Accelerates Diabetic Wound Healing and Improves Wound Tissue Strength in db/db Mice
Authors: Balaji Swathi , Sheikh Abdul Q. , Morris Lee , Lim Foong Y. , Crombleholme Timothy M. , Narmoneva Daria A.
Published: July 2013

Chronic ulcers are a leading cause of morbidity in diabetic patients. Diabetes is associated with major changes in the wound microenvironment and disruption of normal wound healing process, characterized by a prolonged inflammatory phase with elevated levels of wound proteases and increased degradation of extracellular matrix (ECM) components [1]. This impedes wound healing due to a lack of provisional matrix, impaired recruitment and survival of endothelial (EC) and endothelial precursor (EPC) cells, and insufficient neovascularization, resulting in delayed healing. Therefore, strategies focused on restoring the diabetic wound microenvironment by decreasing ECM degradation and promoting neovascularization are promising for development of new therapies to treat chronic diabetic ulcers.
Velocity Workspaces of the Normal Human Knee
Authors: Fuller J. E. , Brown G. A. , Murphy M. C.
Published: July 2013

The human knee is a joint in the musculoskeletal system, and as such, its main function is to allow motion between the thigh and shank of the human lower limb. The development of an analysis technique that, given a set of constraints, maps out all possible knee motions, could offer much information and insight into studies of knee biomechanics. The study of the kinematics of the human knee is one discipline where the construction of this type of information could provide new perspectives on old problems, meaningful information on current questions, and possible direction to future work. Once a geometric model has been developed, the natural place to begin with respect to kinematic analysis is position analysis. The construction of all possible positions and orientations one rigid body may assume relative to some other rigid body is a general description of what displacement workspace analyses attempt to accomplish. It is highly probable that information useful to the study of the biomechanics of the human knee is inherently contained within workspace analyses based on the constraint systems of the joint. Investigation of a relatively simple model, including representations for constraints dictated by the four major ligaments, gives insight into many aspects of the joint biomechanics. For example, the addition and exclusion of ligaments to a workspace model showed noticeable changes in the shape, geometry and size of the two dimensional cross-sections of the displacement workspace. Such information may allow investigators to develop strategies for affecting the allowable displacements and trajectories in similarly constrained joints, in vivo (Fuller, et al., 2000).
A Computational Investigation of Murray’s Law Using 3-D Navier Stokes Solutions and Derivative-Free Optimization
Authors: Sengupta Dibyendu , Marsden Alison L.
Published: July 2013

Murray’s law has been the subject of continual investigation since its derivation in 1926. In his original work Murray solved a simple analytical optimization problem to minimize power requirements, balancing flow rate and metabolic function to find the optimal relationship between the radius of a parent and daughter vessel in a bifurcation along with the bifurcation angle. The cost function used in his work was the sum of a pressure loss term and a metabolic cost term. Minimizing this cost function, Murray derived the following relationship between parent and daughter vessels, rpα=rd1α+rd2α and an angle between the branches of 37.5°.
Shear Stress Induces Time- and Domain-Dependent Changes in Lipid Dynamics of Endothelial Cell Membranes
Authors: Tabouillot Tristan , Muddana Hari S. , Butler Peter J.
Published: July 2013

Endothelial cells (ECs) form the inner lining of the blood vasculature and are exposed to shear stress (τ), the tangential component of hemodynamic forces. ECs transduce τ into biochemical signals possibly via EC-membrane perturbations. We have previously used confocal-FRAP on the DiI-stained plasma membranes of confluent cultured bovine aortic ECs (BAECs) to show that τ induces a rapid, spatially heterogeneous, and time-dependent increase in the lateral diffusion of the fluorescent lipoid probe in the BAEC membrane [1]. We now present evidence at the single molecule level that shear stress differentially perturbs membrane domains that are defined by their selective staining by lipoid dyes (DiI) of differing alkyl chain lengths. This study is the first to directly measure perturbation by shear stress of endothelial cell membrane microdomains.
Computer Modeling of the Patellofemoral Joint Instability: Patella Inherent Geometry Influence on Stress and Loading
Authors: Amirouche Farid , Gonzalez Mark , Goldstein Wayne , Derhake Adam , Dudas Barbara , Tanushri Madhuri
Published: July 2013

Despite a large range of surgical options, treatment of patellofemoral instability continues to be a challenging clinical problem. Currently, there have been a number of computer models developed to try and better define the stabilizing forces about the patellofemoral joint. However, most of these studies have focused on patellofemoral contact pressures, omitting evaluation of patellar stability in the first 30° of knee flexion. The purpose of this study was to reconstruct a pathologic and normative patellar shape within a computer model based on previously described morphologic ratios. We then applied physiologic force vectors to each patellar shape and calculated the stress and moment about each. We hypothesized that individuals with a pathologic patellar shape would have internal stress and moments about the patella which could predispose them to instability. We found that there were significant differences in patterns of stress, strain, and internal displacement about the control and study patellar shapes. This study suggests that a change of patellar shape could have significant effects on the stresses and moments about the patella. Future studies in which calculations of moments could be performed on a series of control and study patellar groups could further define this difference. Dynamic simulations of the control and study patellar shapes could also visually demonstrate the difference in patellar translation. In the future, the results of patellofemoral modeling could be applied to individual patients to more accurately detail an individual treatment plan.
An Experimental Investigation of the Quasi-Steady Assumption in Speech
Authors: Erath Byron D. , Plesniak Michael W.
Published: July 2013

Human speech is initiated when the lungs achieve a critical pressure forcing the vocal folds apart, expelling air through the glottis, and beginning self-sustained oscillations. The oscillations arise due to coupling between the aerodynamic forces and the structural properties of the vocal folds. During each phonation cycle the glottis transitions from a convergent channel upon opening, to a uniform, and finally a divergent channel before closing and repeating the cycle. The resulting pulsatile flow field which emanates from the vocal folds forms the raw component of speech.
The Effects on the Strength of UBM Extracellular Matrix Under Stent Loading: An Experimental and Numerical Study
Authors: Callanan Anthony , Walsh Michael , McGloughlin Tim
Published: July 2013

Arterial diseases are a common cause of death in the western world. The last two decades has seen vast improvements in scanning, screening, prognosis and symptom recognition, resulting in a greater number of treatments. A common treatment procedure used is bypass grafting which currently utilize synthetic graft materials, internal thoracic artery, and autologous vein. These treatments are invasive surgical procedures and can have low patency. An alternative treatment for these conditions is endovascular surgery. However these devices have problems such as restenois, migration and stent fracture. Improved design and drug elution have been utilized to enhance the performance, with limited success. The application of Tissue engineering scaffolds to enhance device performance has had limited studies. A Number of studies have looked at Small Intestine Submucosa in stenting applications [1, 2]. One study implanted an ECM (SIS) stent-graft into 8 sheep. The study concluded that the ECM stent graft successfully treated simple and ruptured AAA’s. Another study investigated a stent graft arrangement in the femoral arteries of sheep. The study found that SIS coated stent preformed better than that of PTFE covered stent grafts.
Data Acquisition for Specimen-Specific Computational Models
Authors: Kersh Mariana E. , Ploeg Heidi-Lynn , Shin Mike , Siggelkow Eik , Muenchinger Marc
Published: July 2013

Advances in medical imaging techniques and computing power have allowed for the creation of sophisticated joint models that include anatomical soft tissue geometries. However the models still require experimental data of the joint’s mechanical response in order to validate the model and accurately predict joint biomechanics. Experimental methods to acquire data of the joint’s mechanical response have a long history in biomechanics [1], but it has been found that the validation of models [2] based on previously collected experimental data has been difficult because of the large inter-specimen variability. A shift, therefore, has taken place emphasizing the development of specimen specific models. Our aim was to develop a method by which the mechanical response of the knee could be measured and used as input and validation data for a specimen specific computational model.