bluuebunny/crossref_metadata_2025 huggingface dataset:
Trajectory-Based Tissue Engineering for Cartilage Repair: Correlation Between Maturation Rate and Integration Capacity
Authors: Fisher Matthew B. , Söegaard Nicole , Steinberg David R. , Mauck Robert L.
Published: January 2014

Given the limitations of current surgical approaches to treat articular cartilage injuries, tissue engineering (TE) approaches have been aggressively pursued over the past two decades. Although biochemical and biomechanical properties on the order of the native tissue have been achieved (1–5), several in-vitro and in-vivo studies indicate that increased tissue maturity may limit the ability of engineered constructs to remodel and integrate with surrounding cartilage, although results are highly variable (2, 6–8). Thus, “static” measures of construct maturity (e.g. compressive modulus) upon implantation may not be the best indicators of in-vivo success, which likely requires implanted TE constructs to mature, remodel, and integrate with the host over time to achieve optimal results. We recently introduced the concept of “trajectory-based” tissue engineering (TB-TE), which is based on the general hypothesis that time-dependent increases in construct maturation in-vitro prior to implantation (i.e. positive rates) may provide a better predictor of in-vivo success (9). As a first step in evaluating this concept, in the current study we hypothesized that time-dependent increases in equilibrium modulus (a metric of growth) would be correlated to ability of constructs to integrate to cartilage using an in-vitro assay. To test this hypothesis, the current objective was to determine and model the time course of maturation of TE constructs during in-vitro culture and to assess the ability of these constructs to integrate to cartilage at various points during their maturation.
Patient Specific Stent Malapposition in Challenging Anatomy: An FEA Methodology to Understand Numerically the Extent of Malapposition of Latest Generation Stents
Authors: Ragkousis Georgios E. , Curzen Nick , Bressloff Neil W.
Published: January 2014

Stent malapposition is a common feature of percutaneous coronary intervention (PCI) particularly in challenging anatomy, and is associated with complications such as stent thrombosis and restenosis. Such lesions can be characterized by long, eccentric, calcified and tortuous geometry. For the purpose of this work, a patient specific right coronary artery stenosis was reconstructed pre-PCI so that virtual FEA simulations of current generation stent could be conducted to model realistic “stenting” conditions. The results show that from the proposed simulation methodology, quantitative and qualitative outcomes can be provided with insight into the development of stent malapposition.
Changes in the Mechanical Properties of Arterial Elastin With Cholesterol Effect
Authors: Sun Hyung Jin , Wang Yunjie , Zhang Katherine Yanhang
Published: January 2014

Elastin is a protein in the extracellular matrix that provides critical mechanical properties of elasticity and extensibility to many connective tissues, including arteries. Such properties of elastin allow arteries to accommodate deformations encountered during physiological functions. Elastin is subjected to changes in mechanical properties upon exposure to various chemical environments. Elastin is a hydrophobic protein, which makes it an attractive site for the deposition of hydrophobic ligands such as cholesterol [1]. Cholesterol is a type of lipid that gradually builds up along arterial wall with aging and pathological conditions.
Tissue Engineered Tumor Microvessels to Study the Role of Flow Shear Stress on Endothelial Barrier Function
Authors: Buchanan Cara F. , Voigt Elizabeth , Vlachos Pavlos P. , Rylander Marissa Nichole
Published: January 2014

As solid tumors develop, a variety of physical stresses arise including growth induced compressive force, matrix stiffening due to desmoplasia, and increased interstitial fluid pressure and altered flow patterns due to leaky vasculature and poor lymphatic drainage [1]. These microenvironmental stresses likely contribute to the abnormal cell behavior that drives tumor progression, and have become an increasingly significant area of cancer research. Of particular importance, is the role of flow shear stress on tumor-endothelial signaling, vascular function, and angiogenesis. Compared to normal vasculature, blood vessels in tumors are poorly functional due to dysregulated expression of angiogenic growth factors, such as vascular endothelial growth factor (VEGF) or the angiopoietins. Also, because of the abnormal vessel structure, blood velocities can be an order of magnitude lower than that of normal microvessels. Recently published work utilizing intravital microscopy to measure blood velocities in mouse mammary fat pad tumors, demonstrated for the first time that shear rate gradients in tumors may help guide branching and growth of new vessels [2]. However, much still remains unknown about how shear stress regulates endothelial organization, permeability, or expression of growth factors within the context of the tumor microenvironment.
The Viscoelastic Properties of Mouse Embryonic Salivary Glands
Authors: Koppes Ryan A. , Mason Andrew K. , Peters Sarah B. , Ray Shayoni , Larsen Melinda , Corr David T.
Published: January 2014

Normal organ development, function, and repair are coordinated by interactions between the epithelium and the surrounding stromal cell populations. Cellular function and homeostasis are controlled by an array of chemical and physical cues originating from the cells themselves and from the surrounding extracellular matrix (ECM). Both the endogenous cell population and ECM modulate and rely on the maintenance of basal level of tension within the tissue as a cue for growth and differentiation [1]. Furthermore, the loss of this tensional homeostasis is synonymous with many pathological conditions including; cancer, wound healing, and degenerative diseases [2].
Small Scale Flow Structure Evolution During Mechanical Heart Valve Closure
Authors: Mousel J. , Udaykumar H. S. , Chandran K. B.
Published: January 2014

Despite half a century of use, mechanical heart valves still require further research to reduce the non-physiologic nature of the flow field, which is the source of potential medical complications, of which the most serious complication is thrombus formation [1]. In the systolic phase of the flow, excessive fluid stresses are generated by the non-physiologic flow patterns [2, 3]. In the closed valve position, a large pressure gradient is imposed across the device which leads to the generation of strong and damaging small-scale leakage flows that entrain platelets such that they are exposed to elevated stresses for excessive time durations [4–6].
High-Throughput Microtissue Contractility Assay for In Vitro Analysis of Vascular Mechanics
Authors: Hald Eric S. , Win Zaw , Scheitel Marianne R. , Alford Patrick W.
Published: January 2014

Vascular smooth muscle (VSM) plays a key role in regulation of vascular mechanics through modulation of contractile tone. Studies suggest that mechanical or biochemical perturbation can lead to dysfunctional VSM behavior [1, 2]. This aberrant contractility may play a role in vascular dysfunction ranging from cerebral vasospasm to aneurysm genesis.
Effects of Freeze-Thaw Cycling on Material Properties of Cancellous Cervine Bone as Characterized by Nanoindentation
Authors: Landauer Alexander K. , Yuya Philip A. , Kuxhaus Laurel
Published: January 2014

Cancellous bone is an important load-bearing component of whole bone, and due to the plate-and-rod nature of trabeculae, small-scale testing is required to measure material parameters for use in modern analytic techniques such as finite element modeling [1, 2]. These material properties are measurable via nanoindentation techniques. During nanoindentation, the indenter tip is forced into the surface of the material while the applied load and tip displacement are monitored. Using these data, along with the tip’s cross-sectional area, mechanical properties are determined. Dynamic testing quantifies viscoelastic response and can obtain material response parameters such as storage and loss moduli. During dynamic testing, a low magnitude sinusoidal force is superimposed on a constant static force. The displacement response is measured at the same frequency as the applied oscillating force, and the resulting phase lag is related to material damping [3].
Inverse Finite Element Analysis of the Indentation Response of Human Cervical Tissue
Authors: Myers Kristin , Yao Wang , Yoshida Kyoko , Vink Joy , Zork Noelia , Wapner Ronald , Oyen Michelle
Published: January 2014

The mechanical function of the cervix is crucial during pregnancy when it is required to resist the compressive and tensile forces generated from the growing fetus. Pathologies of the cervical extracellular matrix (ECM), premature cervical remodeling, and alterations of cervical material properties have been implicated in placing women at high-risk for preterm birth (PTB). To understand the mechanical role of the cervix during pregnancy and to potentially identify etiologies for PTB, the overall goal of our group is to quantify ECM-material property relationships in normal and diseased human cervical tissue. In this study we present an inverse finite element analysis (IFEA) that optimizes material parameters of a viscoelastic material model to fit the stress-relaxation response of excised tissue slices to spherical indentation. Here we detail our IFEA methodology, report viscoelastic material parameters for cervical tissue slices from nonpregnant (NP) and pregnant (PG) hysterectomy patients, and report slice-by-slice data for whole cervical tissue specimens.
Chondroitinase-ABC Digestion and Dynamic Loading Increase Tension-Compression Nonlinearity in Tissue-Engineered Cartilage
Authors: Kelly Terri-Ann N. , Roach Brendan L. , Mackenzie-Smith Charles R. , Nover Adam B. , Estell Eben G. , O’Connell Grace D. , Ateshian Gerard A. , Hung Clark T.
Published: January 2014

Native articular cartilage exhibits tension-compression nonlinearity (TCN), where the compressive modulus is lower than its relatively high tensile modulus [1–2]. TCN produces in restricted lateral expansion of the tissue upon axial compression. We previously demnostrated that osmotic swelling can be used to measure the TCN of engineered cartilage by placing the tissue in an initial state of tensile strain. Incremental application of compression can be used to study the tissue’s mechanical properties as it transitions from tension to compression [3]. Although engineered cartilage is able to achieve the Young’s modulus (E Y) and glycosaminoglycan (GAG) content of native tissue, the collagen content and dynamic modulus (G*) consistently underperform the native tissue. Removing GAG with chondroitinase ABC (cABC) has been shown to significantly decrease the tissue properties immediately after digestion but the properties rebound, with improved collagen content and G* compared to undigested controls [4]. Furthermore, we have previously shown that cABC digestion significantly increases TCN in engineered cartilage [3]. Dynamic loading (DL) has been shown to significantly increase the mechanical properties without significantly altering biochemical composition of engineered cartilage, however the mechanism through which DL modulates the mechanical strength of engineered cartilage may be due in part to improved extracellular matrix (ECM) organization [5]. We therefore hypothesize that cABC digestion and DL will improve the tensile properties of engineered cartilage.
Repeatability, Reproducibility, and Calibration of the MyotonPro® on Tissue Mimicking Phantoms
Authors: Dougherty John , Schaefer Emily , Nair Kalyani , Kelly Joseph , Masi Alfonse
Published: January 2014

The MyotonPro® (Myoton AS, Tallinn, Estonia) is commonly used to quantify stiffness properties of living tissues in situ. Current studies quantify the dynamic stiffness properties of living tissues, but do not validate or compare these measurements to a standardized method. Additionally, living tissue, being dynamic in nature, presents much variability in data collection. To address these issues this study focuses on the repeatability and reproducibility of the MyotonPro® on polymeric gel-based tissue phantoms. In addition, a correlation study is also performed to translate dynamic stiffness to a more standardized property, Young’s modulus. Such studies help to confirm the reliability of the measurements obtained in situ.
In Situ Calcium Signaling of Chondrocytes Under Non-Serum and Serum Culture
Authors: Zhou Yilu , Resutek Lauren , Wang Liyun , Lu X. Lucas
Published: January 2014

Chemically defined serum-free medium has been shown to maintain the mechanical properties of cartilage allografts better than serum supplemented medium during long-term in vitro culture [1]. Little is known about this beneficial mechanism at a cellular level. Intracellular calcium ([Ca2+]i) signaling is one of the earliest responses in chondrocytes under mechanical stimulation [2]. It was recently found that calcium signaling is involved in the regulation of chondrocyte morphology changes and its short-term anabolic and catabolic responses under mechanical stimulation [3]. In this study we hypothesized that the beneficial mechanisms of serum-free culture could be indicated by the spatiotemporal features of [Ca2+]i signaling of chondrocytes in situ. We aimed to: (i) compare the in situ spontaneous [Ca2+]i responses of chondrocytes cultured in medium with and without serum; (ii) investigate the correlation between the [Ca2+]i responses of chondrocytes and the biomechanical properties of cartilage explants.
A Treatment for Chronic Deep Venous Insufficiency Utilizing Induced Pluripotent Stem Cell Derived Endothelial Cells
Authors: Jones Casey M. , Mirza Kasim L. , Blakley Bradley J. , Pavcnik Dusan , Hinds Monica T.
Published: January 2014

Chronic deep venous insufficiency (CDVI) is a disease caused by incompetent venous valves in the deep veins which result in venous reflux and pooling of blood in the lower extremities. Symptoms include edema, skin changes, and ulceration. It is estimated that over six million people in the United States are affected by this disease and symptoms can be recurring, leading to an underestimation of the prevalence. The current treatments of CDVI are management techniques to encourage blood flow and oxygen transport, including compression, elevation, and exercise; strategies to repair or replace the incompetent valves are lacking.
Imaging-Based Multiscale Models of the Respiratory System That Account for Regional Heterogeneity in Health and Disease
Authors: Kabilan S. , Einstein D. R. , Jacob R. E. , Carson J. P. , Kuprat A. P. , Minard K. R. , Corley R. A.
Published: January 2014

Multiscale computational fluid dynamic (CFD) models are fast gaining importance in the field of respiratory systems modeling due to recent advancements in experimental and computational techniques. These models couple imaging-based, physiologically realistic, three-dimensional (3D) geometries to lower-dimensional ordinary differential equations (ODE) or partial differential equations (PDE) that represent the unseen lung. Local deviations from nominal heterogeneity and compliance in disease states such as emphysema and fibrosis have both important clinical and pathological implications. Hence, it is important to incorporate regional heterogeneity in the CFD models while modeling airflow characteristics, aerosol deposition, drug delivery, and risk assessment.
Predictive Modeling and Biomechanical Microengineering of Mesenchymal Stem Cells: A High Content Screening Platform to Enhance Lineage Specific Differentiation
Authors: Paul Amit , Franz David , Yahya Sumaira , Sun Shan , Cho Michael
Published: January 2014

Recent evidence suggests that stem cell differentiation can be regulated by modulation of the cell’s biomechanics. The cytoskeletal structures and arrangements in stem cells undergoing differentiation are dramatically altered, and these alterations vary by lineage. The complexity of events associated with the transformation of these precursor cells leaves many questions unanswered about morphological, structural, proteomic, and functional changes in differentiating stem cells. A thorough understanding of stem cell behavior, both experimentally and computationally, would allow for the development of more effective approaches to the expansion of stem cells in vitro and for the regulation of their commitment to a specific phenotype.
Blood-Tumor Barrier Normalization Effects on Cytotoxic Drug Delivery to Brain Tumors
Authors: Pishko Gregory L. , Nasseri Morad , Gahramanov Seymur , Muldoon Leslie L. , Neuwelt Edward A.
Published: January 2014

The blood-brain barrier (BBB) restricts delivery of anti-cancer drugs to brain tumors, but the leaky neovasculature of the blood-tumor barrier (BTB) permits systemically delivered cytotoxic agents to reach the tumor. Anti-angiogenic therapies such as bevacizumab (BEV) have been shown to “normalize” brain tumor vasculature,1 but the impact on chemotherapy delivery remains unclear.2 The goal of this study was to use magnetic resonance imaging (MRI) to investigate the consequences of BTB normalization, via BEV, on temozolomide (TMZ) chemotherapy. Non-invasive MRI techniques were used to track the transport of a chemotherapy surrogate, a low molecular contrast agent (Gd-DTPA), in an intracerebrally implanted human glioma. MRI-derived Gd-DTPA concentration curves were fit to a transvascular exchange model to measure vascular permeability changes and were used to quantify initial area under the gadolinium curve (IAUGC) over the course of treatment.
Validation of Finite Element Lower Extremity Model Using Drop Tower Testing
Authors: Bertucci Robbin , Prabhu R. , Horstemeyer M. F. , Sheng James , Liao Jun , Williams Lakiesha
Published: January 2014

Explosions are the leading cause of death on the battlefield [1]. These explosives, such as bombs and mines, generate shock waves which stimulate large accelerations and deformations. The resulting loads pose serious threats to military and civilians if not sufficiently evaluated and protected. The use of anti-vehicle landmines has become extremely common. Due to lower extremities being in direct contact with the floor of vehicles, the lower extremities are commonly injured during explosions [2]. These injuries can be seriously fatal. Although experimental studies have been performed to advance these understandings [2], limited progress has been made in computational analysis of shock waves on the lower extremity.
Biomechanical Response of Rats Under a Wide Range of Blast Overpressures in Blast Injury Animal Models
Authors: Chandra N. , Skotak M. , Wang F.
Published: January 2014

We evaluated the acute (up to 24 hours) pathophysiological response to primary blast using a rat model and helium driven shock tube. The shock tube generates animal loadings with controlled pure primary blast parameters over a wide range of field-relevant conditions. The biomechanical loading was evaluated using a set of pressure gauges mounted on the surface of the nose, in the cranial space and in the thoracic cavity of cadaver rats. The mortality rates were established using anesthetized rats exposed to a single blast at five peak overpressures over a wide range of shock intensities (130, 190, 230, 250 and 290 kPa). We observed 0% mortality rates in 130 and 230 kPa groups, and 30%, 24% and 100% mortality rates in 190, 250 and 290 kPa groups, respectively. The intracranial pressure (ICP) oscillations recorded for 190, 250 and 290 kPa groups are characterized by higher frequency (10–20 kHz) than in other two groups (7–8 kHz). The acute bradycardia and moderate lung hemorrhage were noticeable in all groups of rats exposed to the shock wave loading. The onset of both corresponds to 110 kPa peak overpressure, according to the dose-response models. The immunostaining against immunoglobulin G (IgG) of brain sections of rats sacrificed 24-hours post-exposure indicated the diffuse blood-brain barrier breakdown in the brain parenchyma. We observed that the acute response as well as mortality is a non-linear function of peak overpressure and impulse ranges explored in this work.
Direct Optical Estimation of Deformation Gradient Tensors Using Lucas-Kanade Digital Image Warping
Authors: Boyle John J. , Genin Guy M. , Kume Maiko , Pless Robert B. , Thomopoulos Stavros
Published: January 2014

Mechanical characterization of inhomogeneous and/or geometrically complex biological tissues requires precise and accurate determination of strain fields. Digital image correlation is a well established technique for determining strain fields on the surfaces of deforming materials. The technique involves matching patterns between pairs of images to estimate the displacement of certain regions or features on a sample. 2 Image correlation has also been used to track deformations in dynamic magnetic resonance images of heart and brain. 3
A Novel, Laser-Based Technique to Fabricate and Precisely Pattern Cell-Encapsulated Alginate Microbeads
Authors: Kingsley David M. , Dias Andrew D. , Chrisey Douglas B. , Corr David T.
Published: January 2014

Microbeads are three-dimensional, generally spherical microstructures that are currently being investigated for applications in tissue engineering and for delivery of drugs, proteins, and DNA [1, 2]. Current microbead fabrication devices such as electrostatic bead generators, microfluidic devices, and micro-vibrators, function by using cross-linkable polymers into a crosslinking solution, such as calcium chloride in the case of alginate. These procedures allow for the controlled manipulation of microbead size, e.g., increasing electric field voltage for the electrostatic bead generator during polymer extrusion. Popular devices such as electrostatic bead generators are limited to polyelectrolyte materials because of the electric field extrusion method [3]. In addition, despite their ability to create monodispersed beads of different size, none of these technologies can precisely control microbead placement.
Comparing In Vivo Head Impact Kinematics From American Football With Laboratory Drop and Linear Impactors
Authors: Hernandez Fidel , Shull Pete B. , Cam Bruce , Wu Lyndia , Shultz Rebecca , Garza Dan , Camarillo David B.
Published: January 2014

Roughly 5% of all collegiate and high school American football players suffer a concussion each season [1]. Concussions and repetitive sub-concussive trauma can have measurable effects on brain function and neurophysiological changes [2]. Several studies have suggested that a combination of linear and angular kinematic measures may be predictive of concussion [3, 4]. Presently, laboratory testing and analysis of purely linear kinematics is used to design and assess the safety of protective headgear. However, it is not known how well existing laboratory tests recapitulate angular kinematics. In this study, we analyze combinations of linear and angular head kinematics experienced by players on the field. This study sought to answer the question: how well do the twin-wire drop test apparatus and a spring-driven linear impactor reproduce the combination of linear and angular head impact kinematics experienced in vivo by players of American football?
Optimizing the Design of a Device Targeted Towards Facilitating Adequate Neonatal Resuscitation in Low Resource Environments
Authors: Dria Stephen , Harfmann Kaitlyn , Lee Christopher (Xiang) , Narrow David , Thapa Kusum , Sanghvi Harshad , Myklebust Helge , Acharya Soumyadipta
Published: January 2014

Annually, there are 4 million global neonatal deaths, which account for over 38% of deaths in children under the age of five. 1 Most of these deaths occur in developing nations and resource constrained environments. Researchers have identified 16 available interventions, and with 99% coverage, these interventions can prevent 41–72% of all global neonatal deaths. 2
Coupled Poroviscoelastic and Optical Monte Carlo Simulation of Dynamic Light Transport Through Indented Soft Tissue
Authors: Vogt William C. , Rylander Christopher G.
Published: January 2014

Biological tissues are heterogeneous materials that may be considered mixtures of water, proteins, and cells. The large mismatch in refractive index between these constituents causes tissues to be highly turbid, diffusing light and limiting the efficacy of optical diagnostic and therapeutic techniques [1]. Mechanical optical clearing is a technique for reducing tissue scattering and absorption using controlled tissue deformation. Mechanical optical clearing is performed using indentation to locally modify tissue optical properties, including refractive index [2] and reduced scattering coefficient [3]. This effect is attributed to transient changes in tissue water distribution as a result of interstitial fluid flow due to tissue compression. In this study, we have developed a multi-domain mathematical framework for simulating mechanical optical clearing effects on tissue mechanical and optical behavior, including hyperelasticity, viscoelasticity, porous flow, and light transport. This model was then fitted to mechanical force data and used to predict experimentally measured optical transmission.
Tibio-Femoral Contact Pressure During Gait
Authors: Stylianou Antonis P. , Kia Mohammad , Guess Trent M.
Published: January 2014

Detailed analysis of knee joint loading during ambulatory activities is of utmost importance for improving the design of total knee replacement components and the outcome of the surgical procedures. A dynamic computational model capable of concurrent predictions of muscle, ligament, and articular surface contact forces would be the ideal tool for enhancing our knowledge of these in-vivo loads and for exploring different loading scenarios.
Right Ventricular Dysfunction in Pulmonary Arterial Hypertension: Cellular and Hemodynamic Changes in a Mouse Model
Authors: Wang Zhijie , Patel Jitandrakumar R. , Schreier David A. , Moss Richard , Hacker Timothy A. , Chesler Naomi C.
Published: January 2014

Pulmonary arterial hypertension (PAH) is the most severe form of pulmonary hypertension due to its rapid progression to right ventricular (RV) failure. Until the recent combination of chronic hypoxia with VEGF receptor blockage by SU5416 [1], there was no mouse model for severe PAH. This new model (HySu) recapitulates hallmarks of human PAH, especially distal arteriolar neointima formation and obliteration [1]. However, the changes in RV function in this model have not been examined. Here we investigate the hypothesis that the HySu mouse model mimics the progression of RV dysfunction found in PAH clinically from compensatory to maladaptive RV remodeling.
Mismatches in Stiffness Between the Vagina and Transvaginal Mesh Lead to Stress Concentrations Near an Anterior Wall Incision
Authors: Thunes James , Pal Siladitya , Moalli Pamela , Abramowitch Steve , Maiti Spandan
Published: January 2014

Trans-vaginal synthetic meshes have been commonly used to treat pelvic organ prolapse. Recently however, concerns related to the use of trans-vaginal mesh have arisen due to the high incidence of complications. The FDA received more than 3000 reports of complications related to these procedures between 2008 and 2010. Of the women who undergo this procedure, approximately 30% will require additional surgery within 4 years [1]. The most common complication reported was an erosion of the vaginal wall [2]. We hypothesize that mismatch between the mechanical properties of the vaginal tissue and the synthetic mesh lead to higher stresses in the vaginal tissue and subsequently to a higher risk of mesh erosion.
E-Beam Nanopost Arrays Reveal That Glycoprotein Ib-IV-X Complex and Von Willebrand Factor Interactions Transmit Platelet Cytoskeletal Forces
Authors: Feghhi Shirin , Munday Adam D. , Tooley Wes W. , Lopez Jose A. , Sniadecki Nathan J.
Published: January 2014

We have developed a new tool to measure the contractility of single platelets. This tool consists of an array of nano-scale polydimethylsiloxane (PDMS) posts. Von Willebrand factor (VWF) and a recombinant protein encompassing the GPIb-IX-V binding region of VWF (A1 domain) were used to study the role of GPIb-VWF interactions in platelet contractility. Platelets were treated with AK2 and 7E3 antibodies to block platelet adhesion through receptors GPIb and α IIbβ 3, respectively. Platelets treated with these antibodies showed reduced spread area and forces in comparison to untreated platelets on VWF. Furthermore, platelets were able to generate contractile forces on substrates coated with A1 domain of VWF. These results suggest that platelet contractile forces can be transmitted through a non-integrin receptor, such as GPIb.
Accuracy and Feasibility of Dual Fluoroscopy and Model-Based Tracking to Quantify In Vivo Hip Kinematics During Clinical Exams
Authors: Kapron Ashley L. , Aoki Stephen K. , Peters Christopher L. , Bey Michael J. , Zauel Roger , Anderson Andrew E.
Published: January 2014

Chondrolabral damage in hips with femoroacetabular impingement (FAI) may result from motion conflict due to abnormal bony morphology. Clinical range of motion and skin-marker motion analysis studies indicate that kinematics are altered in FAI hips, but assessments are limited due to subjective goniometer alignment, skin motion artifact, and imprecise estimations of the hip joint center. Computer simulations of collision between the femur and pelvis suggest that FAI reduces range of motion, but assume a fixed center of rotation and neglect bulk soft tissue restraints. Thus, hip impingement has not been accurately quantified in vivo.
Direct Structured Finite Element Mesh Generation From Three-Dimensional Medical Images
Authors: Bayat Sharareh , Necsulescu Dan , Labrosse Michel
Published: January 2014

In this work, a new methodology is proposed to automatically construct a structured finite element (FE) mesh from the information contained in patient-specific three-dimensional (3-D) images. Testing of the methodology is presented toward meshing of the human aorta from 3-D synthetic images as well as CT medical images. Promising results are obtained and future directions are discussed.
Inclusion of a Collagen-GAG Sponge Core Improves Tangent Modulus of Multi-Phase PEGDM Hydrogel Constructs
Authors: Kinneberg Kirsten R. C. , Nelson Andra , Paietta Rachel C. , Roberts Justine J. , Harley Brendan A. , Bryant Stephanie J. , Ferguson Virginia L.
Published: January 2014

Nearly 27 million people in the United States suffer from osteoarthritis (OA).[1] While surgical options are available for patients suffering from OA, focal treatments, such as resection and mosaicplasty, rarely succeed in regenerating fully functional cartilage. Tissue engineering holds potential for developing more effective repair strategies.
Experimental Validation of a Computational Algorithm for the Zero Pressure Geometry Derivation of Blood Vessels
Authors: Chandra Santanu , Gnanaruban Vimalatharmaiyah , Seong Jaehoon , Lieber Barry B. , Rodriguez Jose F. , Finol Ender A.
Published: January 2014

Patient-specific computational assessment of biomechanical parameters such as peak wall stress is a promising tool for rupture risk assessment of blood vessels. However, this assessment is dependent on image based modeling of the vasculature [1] and on either structural or fluid-structure interaction analyses performed with numerical models to compute the stress and strain in the vascular wall. Protocols have been successfully derived to develop 3D models of normal and pathological vessels from individual Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) [2]. While the image based models used for these simulations are essentially in a pressurized state (gated to diastolic pressure), the application of physiologic systolic and diastolic pressures to compute stresses and strains is debatable. Therefore, the derivation of a “simulation ready” computational geometry is of great importance to the research community as the accuracy of the computational results is dependent on it.
A Continuum Material Model for Urogynecogical Meshes
Authors: Pal Siladitya , Thunes James , Moalli Pamela , Abramowitch Steven , Maiti Spandan
Published: January 2014

A wide variety of Synthetic polypropylene (PP) meshes are currently being used to restore pelvic organ support for women suffering from pelvic organ prolapse. These meshes are implanted in over 200,000 women annually. However, they are essentially modified abdominal hernia meshes; and, as such, their use in the field of urogynecology has undergone little oversight. With more patients experiencing morbidity, the FDA has released two Public Health Notifications in 2009 and 2011 informing the public about the potential complications associated with urogynecological mesh implantation.
Simultaneous Prediction of Muscle, Ligament and Tibiofemoral Contact Forces via Optimally Tracking Subject-Specific Gait Dynamics
Authors: Thelen D. G. , Choi K. W. , Schmitz A.
Published: January 2014

Computational models are needed to estimate soft tissue loads during movement. It would be ideal to perform such estimates on a subject-specific basis, where the information could be used clinically for assessing injury risk, planning treatment and monitoring rehabilitation outcomes. Musculoskeletal simulation software has evolved to the point that it is now relatively straight forward to estimate muscle forces needed to emulate subject-specific joint kinematics and kinetics [1]. These muscle forces can subsequently be used as boundary conditions in a knee mechanics model to estimate the associated ligament and cartilage loads [2]. However, this serial simulation approach may ignore inherent interactions between musculoskeletal dynamics and internal joint mechanics. That is, cartilage contact forces and ligament tension can potentially contribute to joint moment equilibrium [3]. Further, ligament stretch may allow joint kinematics to vary in a way that affects muscle moment arms and lines of action about the joint. Thus, it would be preferable if muscle, ligament and cartilage contact loads were estimated simultaneously so that these interactions are accounted for. The objective of this study was to incorporate a six degree of freedom tibiofemoral model into an existing subject-specific gait simulation framework [4]. In this study, we introduce the computational model, and then use it to track measured gait dynamics of a subject with an instrumented knee joint replacement. A comparison of the model-predicted and measured tibiofemoral contact forces provides a basis for assessing the validity of this novel co-simulation framework.
Effect of Shoe Stiffness on Injury Produced Under External Rotation of the Foot in Human Cadavers
Authors: Button Keith D. , Davison Mark A. , Braman Jerrod E. , Schaefer Maureen C. , Haut Roger C.
Published: January 2014

Ankle sprain is a common occurrence in sports, accounting for 10–30% of injuries 9. Injury to the lateral ligamentous complex occurs under excessive foot inversion and is known as a “lateral ankle sprain” 1. Injury to the anterior deltoid ligament (ADL), which consists of the tibionavicular ligament (TiNL) and the anterior tibiotalar ligament (ATiTL), is known as a “medial ankle sprain” 13. High ankle sprains occur in the distal tibiofibular syndesmosis, which is comprised of the anterior and posterior tibiofibular ligaments (ATiFL and PTiFL) and the interosseous ligament (IOL) 2. While approximately 85% of ankle sprains are lateral ankle injuries, syndesmotic (high) and medial injuries typically result in more time off the field. The mechanism of both high and medial ankle sprain is commonly ascribed to excessive internal rotation of the upper body, while the foot is planted on the playing surface.
Effects of Body Weight Modification on Internal Knee Contact Forces During Gait
Authors: Kinney Allison L. , Vincent Heather K. , Harman Melinda K. , Coburn James , D’Lima Darryl D. , Fregly Benjamin J.
Published: January 2014

Obesity is commonly considered a risk factor for the development of knee osteoarthritis [1]. Previous studies have shown that reductions in body weight correspond to reductions in total knee joint compressive forces (as calculated by inverse dynamics) [2–4]. A recent study showed that external knee load measurements are not strong predictors of internal knee contact forces [5]. Therefore, direct measurement of knee contact force is important for understanding how body weight changes impact knee joint loading. Force-measuring knee implants can directly measure internal knee contact forces [6].
Biomechanical Cadaveric Analysis of Biotenodesis Screw Versus Bone Tunnel Fixation Methods in Flexor Hallucis Longus Transfers
Authors: Balldin B. Christian , Zide Jacob R. , Liu George T. , Chen Christopher T.
Published: January 2014

The Achilles tendon is the largest tendon in the human body. It connects the gastrosoleus complex to the calcaneus bone in the foot. It thus allows for transfer of force and heel elevation during forward propulsion of the foot in gait. It is also one the most commonly injured tendons. (1). Acute repair or acute intervention for non-operatively treated tendons do well to restore function. However, chronic Achilles tendon ruptures often require tendon transfer rather than attempt at primary repair. The treatment considered the gold standard is the transfer of the flexor hallucis longus (FHL) tendon to the Achilles insertion of the calcaneus (2).
Living Without Breathing: A Study in Extrapulmonary Respiration Using a Novel Oxygen Carrier
Authors: Legband Nathan , Feshitan Jameel , Borden Mark , Terry Benjamin
Published: January 2014

Pulmonary failure results when the lungs experience significant damage and are unable to supply the body and brain with oxygen. Pulmonary failure has many causes including lung cancer, physical trauma, acute respiratory distress syndrome (ARDS), aerosolized bioterrorism agents and diseases such as severe acute respiratory syndrome (SARS), pneumonia, and tuberculosis [1,2].
Effects of Estrogen on Pulmonary Vascular Remodeling in Pulmonary Artery Hypertension
Authors: Liu Aiping , Chesler Naomi
Published: January 2014

Pulmonary artery hypertension (PAH) is a female dominant, fatal disease characterized by progressive increase of pulmonary vascular resistance and loss of compliance. The role of estrogen in these pulmonary vascular changes with PAH progression remains unclear. Our objective was to study the effects of estrogen on pulmonary arterial (PA) remodeling in a mouse model of progressive PAH, created via a combination of a VEGF inhibitor Sugen and chronic hypoxia (SuHx). To quantify PA hemodynamics, we measured in vivo pressure and flow simultaneously in live mice in order to obtain pulmonary vascular impedance, a comprehensive measure of RV afterload. Our results demonstrate that estrogen modifies the relationship between PA resistance and compliance by attenuating PA stiffening, which provides insight into sex differences in PAH progression.
Engineering Meniscus Form and Function via Multi-Layer Cell-Seeded Nanofibrous Scaffolds With Circumferentially Aligned Fibers
Authors: Fisher Matthew B. , Söegaard Nicole , Esterhai John L. , Mauck Robert L.
Published: January 2014

The menisci are crescent-shaped fibrocartilaginous tissues which function to transmit and distribute complex loading patterns between the femur and tibia of the knee joint. Meniscus function in tension arises from highly aligned collagen fibers which run in a circumferential manner between insertion sites on the tibial plateau (1,2). However, the meniscus is often injured, and partial removal of the meniscus represents the most commonly performed orthopaedic surgery, despite the fact that its removal increases the likelihood of osteoarthritis in the long-term (3). Tissue engineered scaffolds have emerged as a promising alternative to replace portions of the damaged meniscus (4). Toward replacement, we have developed aligned nanofibrous scaffolds that can recapitulate the mechanical anisotropy of the meniscus (5,6). More recently, we have developed an approach to replicate the circumferential macroscopic orientation of fibers using a novel electrospinning method (7). However, these organized scaffolds are relatively thin (<1 mm), and so multilayer scaffolds will be required to replicate the anatomic size of the native tissue. Moreover, cellular interactions will be crucial to the long-term function of these scaffolds. Thus, the objective of this study was to evaluate the morphological characteristics and mechanical properties of single layer and multilayer circumferentially aligned (CircAl) scaffolds seeded with mesenchymal stem cells (MSCs) and to compare them to scaffolds featuring linearly aligned (LinAL) fibers. We hypothesized that with increasing time in culture, matrix formed between layers would provide mechanical reinforcement, particularly in CircAl scaffolds where fiber rotation would be more likely to occur.
The Effects of Mechanical and Chemical Stimuli on Mesenchymal Stem Cell Vascular Trans-Differentiation and Paracrine Signaling
Authors: Wingate Kathryn , Tan Yan , Tan Wei
Published: January 2014

Mesenchymal Stem Cells (MSCs) show great promise for the treatment of cardiovascular diseases by tissue engineering and cell therapy. MSCs are particularly useful for vascular therapies as they are easily obtainable, allogenic, trans-differentiate into specific vascular cells, and assist in regenerating vascular tissue through paracrine signaling. [1] However, the mechanisms which direct MSC trans-differentiation and paracrine signaling are not well defined. [2] Incorrect differentiation of MSC can lead to catastrophic side effects such as the development of a dysfunctional endothelium. [3] To safely utilize these cells for the treatment of vascular diseases it is critical to understand the underlying mechanisms that direct MSC differentiation and paracrine signaling.
Meniscectomized Knees Regain Normal Walking Flexion Range of Motion With Time Past Surgery
Authors: Edd Shannon N. , Netravali Nathan A. , Favre Julien , Giori Nicholas J. , Andriacchi Thomas P.
Published: January 2014

Meniscal tears are one of the most common knee injuries with an incidence rate of 60–70 per 100,000 person-years [1]. Although arthroscopic partial meniscectomy, the leading treatment for meniscal tears, decreases pain, the risk of knee osteoarthritis (OA) is four times higher for a meniscectomized knee compared to an uninjured knee [2]. Prior research has shown that meniscectomized knees have reduced sagittal-plane range of motion in the early period following surgery (6 to 18 months) [3–5]. These observations suggest a mechanical pathway to knee OA, in which alteration in ambulatory knee function causes shifts in tibiofemoral cartilage location to unprepared cartilage regions, thus causing damage to the maladapted tissue [6]. While such a mechanical pathway is well documented for knees with reconstruction of the anterior cruciate ligament [7], the paucity of information regarding the walking mechanics of meniscectomized knees at longer term post-operation limits our understanding of the pathway to OA in this population. Particularly, it is unknown whether meniscectomized knees regain normal dynamic range of motion (ROM) in knee flexion with time past surgery. Because regaining ROM alters the mechanical function in the meniscectomized knee, understanding the changes in this gait variable over time may help elucidate the various pathways to OA development in meniscectomized knees.
Determining Heterogeneity in the Scleral Shell Using an Inverse Mechanics Approach
Authors: Ayyalasomayajula Avinash , Vande Geest Jonathan
Published: January 2014

One of the important events leading to loss of vision in primary open-angle glaucoma — the 2 nd leading cause of blindness in the US [1] — is the death of retinal ganglion cells. Previous research has established a strong correlation between elevated intraocular pressure (IOP) and the incidence of glaucoma [2]. Stiffening of ocular tissues (like sclera) and axonal damage in the optic nerve head (ONH) were found to occur in response to elevated IOPs [3, 4]. As such, the biomechanical environment in and around the ONH, which is surrounded by the sclera and through which the visual information exits the eye, could be important in the incidence of this disease. Additionally, race and ethnicity factors were found to affect the incidence of glaucoma [5].
Development of a 1D Model for Assessing the Aortic Root Pressure Drop With Viscosity and Compliance
Authors: Mohammadi Hossein , Cartier Raymond , Mongrain Rosaire
Published: January 2014

Aging and some pathologies such as arterial hypertension, diabetes, hyperglycemia, and hyperinsulimenia cause some geometrical and mechanical changes in the aortic valve microstructure. Cupsal thickening and lost of extensibility (increasing stiffness) are the consequences of these changes in the aortic valve which have a negative impact on the function of the valve [1]. The most frequent form of diseases of the aortic valve is the calcific aortic stenosis which is responsible for 80% of the North American deaths due to valvular heart diseases [2]. In this pathology, calcified nodules on the valve leaflets occur which lead to the thickening and stiffening of the leaflets and restricting the natural motion of the valve which presents an increased resistance to forward blood flow during the ejection phase of the cardiac cycle. To reduce the mortality and morbidity from the aortic stenosis, clinical management and proper diagnosis are essential [3]. Tranvalvular pressure gradient (TPG) and the effective orifice area (EOA), the minimum cross sectional area of the blood flow across the stenosis, are the most commonly used indices for assessing the aortic stenosis [4]. Numerous studies have been done to relate the TPG across the stenosis to the blood flow rate and EOA. Gorlin (1951) was the first to establish a relationship between TPG and EOA [5]. Several studies have reported deviations in valve area calculation by using Gorlin formula. This formula was derived based on some assumptions such as rigid circular orifice, non viscous and steady flow, while valvular orifices are compliant and the flow through them is viscous and pulsatile [6]. Several corrections have been proposed. However, even with these improved formula, significant deviations are still reported [7]. Calark (1978), Bermejo et al (2002) and Garcia et al (2006), by presenting a theoretical model, tried to express TPG in terms of the blood flow rate and EOA [8–10]. None of these studies considered the effect of the aortic root compliance on TPG. Nobari et al reported that the stiffening of the aorta changes the pressure drop and affects the leaflets motion [11]. Therefore, the objective of this study is to develop a 1D model for assessing the aortic pressure drop for the transient viscous blood flow across the aortic stenosis, by taking into account the vessel wall compliance. The derived TPG will be expressed in terms of the surrogate variables which are anatomical and hemodynamic data meaningful and accessible for physicians.
Regularization of Phase-Contrast MRI Velocity Measurements: Initial In Vivo Experience in a Canine Aneurysm Model
Authors: Jiang Jingfeng , Xu Zhengfu
Published: January 2014

According to the US National Institute of Neurological Disorders and Stroke, incidence of reported intracranial aneurysm (IA) rupture is about 0.001%. In other words, there are thus about 27,000 people who may suffer stroke from ruptured cerebral aneurysms each year. The origin and natural history of IAs are closely associated with disturbed hemodynamics though exact mechanisms are unknown.[1, 2] Consequently, blood flow parameters measured from phase-contrast magnetic resonance imaging (PC-MRI) [3, 4] may provide insight not only into factors relevant to the development and progression of IAs but also into their short and long term responses to therapeutic interventions (e.g. coil embolization and stent deployment).