bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Fibers on the Fracture Strength of Bone-Cement Interfaces
Authors: Khandaker Morshed , Utsaha K. C. , Khadka Aaush , Banstola Sandip
Published: January 2014

Background: The interfacial mechanics at the bone-cement or implant-cement interfaces is a critical issue for implant fixation and the filling of tissue defects created by disease. Electro spanning is a process by which fibers with sub-micron diameters can be obtained from an electrostatically driven jet of polymer solution. These fibers have a high surface area to volume ratio, which have numerous engineering applications. The present study is based on the hypothesis that the differences of the surface properties at bone/ cement interface due to incorporation of micro and sub-micron diameters fiber may have significant influence on the quality of bone/cement union.
Parity Negatively Impacts the Uniaxial Mechanical Properties of the Vagina in the Ewe
Authors: Knight Katrina , Moalli Pamela , Palcsey Stacy , Barone William , Abramowitch Steven D.
Published: January 2014

Pelvic organ prolapse (POP) is a common disorder with a profoundly negative impact on the physical and psychological health of women worldwide; however, the exact etiology is currently unknown. Parity, defined as the number of births, is commonly identified as one of the leading risk factors for the development of POP. The objective of this study was to examine the impact of parity on the uniaxial mechanical properties of the sheep vagina along the longitudinal direction. The findings of this study revealed that parity negatively impacts the tangent modulus (54% decrease), tensile strength (54% decrease), and strain-energy density (47% decrease) of the vagina in the ewe (female sheep). Based on similar findings in primate, these data suggest that the ewe may serve as a cheaper alternative for studying the pathogenesis of POP moving forward.
Combined Analysis of Pathology and Hemodynamics of Human Unruptured Cerebral Aneurysm With Thin-Walled Region
Authors: Tobe Yasutaka , Yagi Takanobu , Iwabuchi Yuki , Yamanashi Momoko , Takamura Kenji , Iwasaki Kiyotaka , Umezu Mitsuo , Hayashi Yoshifumi , Yoshida Hirotaka , Nakajima Atsushi , Nishitani Kazutoshi , Okada Yoshifumi , Sugawara Michihito , Hiraguchi Shin , Kubo Toshiro , Kitahara Shigemi
Published: January 2014

Cerebral aneurysms are known as the top reason of subarachnoid hemorrhage (SAH). They are studied in the medical and the engineering field to reveal their pathogenesis, progression, and rupture mechanisms1,2. The pathological studies revealed the site of predilection, rupture rate, the risk factors1, inflammation within the aneurysm, and conditions of endothelial cells (EC) in the aneurysms3. The current pathological analyses of the cerebral aneurysms are all phenomenological and it does not consider the cause-and-effect mechanisms between the mechanical stimulation and the physiological effect although hemodynamics is thought to play an important role in the mechanisms of aneurysms. One reason that the aneurysms’ mechanisms remain unsolved is because the pathology and hemodynamics are studied independently. Purpose of this study is to reveal the relationship of endothelial cell, thickness, and hemodynamics of the cerebral aneurysms by comparing the scanning electron microscope (SEM) analyses, μCT, and the computational fluid dynamics (CFD) analyses of the cerebral aneurysms.
Heparin Leakage by Advective-Diffusive Transport in Central Venous Catheters
Authors: McGah Patrick M. , Barbour Michael , Aliseda Alberto , Gow Kenneth W.
Published: January 2014

Central venous catheters (CVCs) are used as a way to provide adequate access of blood flow for hemodialysis, a common treatment for end-stage kidney disease. During hemodialysis, the catheter must circulate up to 300 mL/min [1] of blood flow to the extracorporeal artificial kidney. Catheters contain two lumens: the inflow lumen provides flow to the artificial kidney, and the outflow lumen returns it to the patient’s circulation. Although catheters are used in the treatment of patients of all ages, this study is motivated by the use of central venous catheters for pediatric applications; the catheter types and calibers available for children are much more limited than for adults, thereby placing children in a further disadvantage and potentially subjecting them to increased risk of complications.
Combined Effects of Scaffold Material and Mechanical Stimulation on the Formation of Tissue Engineered Constructs Using Tendon and Ligament Progenitor Cells
Authors: Breidenbach Andrew P. , Dyment Nathaniel A. , Lu Yinhui , Shearn Jason T. , Rowe David W. , Kadler Karl E. , Butler David L.
Published: January 2014

Tendon and ligament injuries account for one-third of all musculoskeletal injuries [1]. Collagen fibrils in these mechanosensitive tissues transmit forces to mobilize and stabilize joint movement. Donor tissues used to repair these tissues often lack the mechanical properties of the tissue they are replacing. One promising alternative using tissue engineering combines stem/progenitor cells in three-dimensional tissue engineered constructs (TECs).
Modeling a Surrogate Head Response Under Blast Loading
Authors: Hua Yi , Akula Praveen Kumar , Gu Linxia
Published: January 2014

The work is to unravel the wave transmission mechanism through modeling the water-filled polycarbonate shell subjected to blast loading. The shock wave propagation inside a shock tube and the interaction between the shock wave and the surrogate head were captured using the arbitrary Euler-Lagrangian coupling method. Results demonstrated a complex fluid field around the head. Pressure history profiles at anterior and posterior sites of the brain simulant exhibited the typical coup and countercoup pattern, which were attributed to the surface pressure wave (direct loading) and the structural wave in the skull simulant (indirect loading). This study could enhance our understanding on blast-induced traumatic brain injury, leading to novel injury mitigation strategies.
Material Composition Gradients and Protein Release for Tracheal Defect Repair
Authors: Ott Lindsey , Vu Cindy , Farris Ashley , Weatherly Robert , Detamore Michael
Published: January 2014

Windpipe defects result in decreased quality of life for the patient, making breathing, speaking, and swallowing difficult. Disorders of the trachea requiring intervention methods not adequately treated by slide tracheoplasty or cartilage augmentation necessitate the use of prosthetic material to expand the trachea. Furthermore, some donor site morbidity occurs with augmentation techniques and size or shape mismatches are not uncommon. Tissue engineering has the potential to create effective replacement trachea-like tissue for procedures like laryngotracheal reconstruction and may circumvent these problems.
Effect of Anisotropic Permeability of the Superficial Layer on the Frictional Property in Articular Cartilage
Authors: Imade Kyuichiro , Fujie Hiromichi
Published: January 2014

Articular cartilage has a significant lubrication property that has been explained in previous studies by many theories including mixed lubrication, hydrodynamic lubrication, surface gel hydration lubrication, biphasic theory, and so on. However the mechanism of continuously low friction in articular cartilage still remains unclear. Reynaud and Quinn indicated that the hydraulic permeability was significantly anisotropic under compressive strain; the tangential permeability becomes lower than the normal permeability under compression [1]. Meanwhile scanning electron microscopic observation indicated that the superficial layer of articular surface was consisted of close-packed collagen fibers aligning parallel with articular surface and tangling each other in normal cartilage (Fig. 1). It is, therefore, suggested that the permeability is extremely low in the tangential direction when subjected to compressive strain. We have a hypothesis that the unique structure and properties in the articular cartilage superficial layer may improve the lubrication properties [2]. Therefore, we performed an analytical study using a fiber-reinforced poroelastic biphasic model to determine the effect of lateral permeability reduction in the superficial layer on the frictional property of articular cartilage.
Segmentation of Rat Brain MR Images Using Artificial Neural Network Classifier
Authors: Magdoom K. N. , Mareci Thomas H. , Sarntinoranont Malisa
Published: January 2014

Recently MR image based computational models are being developed to assist targeted drug delivery in the brain by helping determine appropriate catheter position, drug dose among others to achieve the desired drug distribution [1–3]. Such a planning might be important to prevent damaging healthier tissues because many of the drugs (e.g. chemotherapeutic agents) are usually toxic and needs to be concentrated in specific regions of interest (e.g. tumor). However, for the image based model to make accurate predictions, it is important to segment the image and assign appropriate tissue properties such as hydraulic conductivity which are known to vary significantly within the brain. For example, it has been experimentally found that drugs injected into brain parenchyma get preferentially transported along the white matter tracts compared to the gray matter regions [4]. Segmenting MR images is a challenging task since the pixel intensities between different regions often overlap, hence traditional approaches based on thresholds might not provide reliable results. In this study, we used multi-layered perceptron (MLP) neural network to segment rat brain MR images into 3 different regions namely white matter (WM), gray matter (GM) and cerebrospinal fluid (CSF).
Aging Endothelial Cells Exhibit Decreased Response to Atheroprotective Shear Stress
Authors: Cheung Tracy M. , Truskey George A.
Published: January 2014

As endothelial cells (ECs) age, morphological and physiological changes occur that may alter macromolecular transport and cause subsequent disease development. ECs in atherosclerotic regions exhibit high cell turnover and high levels of oxidative stress due to transient flow patterns and low and oscillating shear stress. This leads to replicative or stress-induced senescence. Resveratrol indirectly reverses senescence-associated phenotypes via competitive inhibition of cAMP-degrading phosphodiesterases (PDEs). Elevated levels of membrane-associated cAMP activate the cyclic AMP-regulated guanosine nucleotide exchange factor Epac1 which, in turn, leads to guanosine triphosphate (GTP) binding to the small G protein Rap1. GTP bound Rap1 activates the deacetylase SIRTUIN1 (SIRT1) but also causes changes to the cortical cytoskeleton and organization of VE-cadherin mechanosensor in the endothelial junctions (Figure 1).
Variational Viscoelastic-Damage Model for Fiber Reinforced Soft Tissues
Authors: Fancello Eduardo A. , Vassoler Jakson M.
Published: January 2014

Connective soft tissues have a pronounced anisotropic mechanical behavior due to their internal structure, consisting of a quasi isotropic ground substance and anisotropic reinforcement based mostly in elastin and collagen fibers. The objective of this paper is to extend previously proposed model for viscoelastic materials with fiber reinforcement making it capable to represent two important phenomena: the so-called Mullins effect and the softening at excessive strains. The model is based on a variational, thermodynamical consistent framework based on an incremental potential that allows for the representation of different dissipative material by simply changing the expression of potential functions and for the obtention of symmetric constitutive tangent matrices. Numerical examples show the capability of the proposed model to mimic with appreciable accuracy the experimentally observed mechanical behavior of soft tissues.
Effect of the Anastomotic Angle on the Wall Shear Stress Profiles in the Arteriovenous Fistulae
Authors: Conners Briana M. , Rajabi-Jaghargh Ehsan , Banerjee Rupak K.
Published: January 2014

A significant number of arteriovenous fistulae (AVFs) fail to mature to support hemodialysis. Hemodynamic parameters, mainly wall shear stress (WSS), are believed to play a crucial role in the maturation or failure of AVFs. Our goal is to study the effects of the AVF configuration on the WSS profile. Idealized AVFs with 90°, 60°, and 30° anastomotic angles were created based on our previous experimental data from an in-vivo swine model [1]. The hemodynamic parameters were then obtained using numerical techniques under steady state condition. The average WSS values for our models were within range of the swine model average WSS (= 174.9±64.6 dyne/cm 2). For all AVFs, WSS was higher along the bend. The highest WSS occurred on the outer wall (OW) of the 30° AVF (= 613 dyne/cm 2) compared to the 60° (= 407 dyne/cm 2) and 90° AVFs (= 329 dyne/cm 2). WSS on the inner wall (IW) of the bend was negative with the smallest magnitude in the 90° AVF (= −91 dyne/cm 2) compared to the 60° (= −172 dyne/cm 2) and 30° AVFs (= −169 dyne/cm 2). In addition, the maximum difference in WSS (ΔWSS: measure of axial WSS gradient) was less for the 90° AVF (= 158 dyne/cm 2) than the 60° (= 170 dyne/cm 2) and 30° AVFs (= 414 dyne/cm 2). A similar trend was found on the OW with ΔWSS of 161, 405, and 870 dyne/cm 2 for the 90°, 60°, 30° AVF, respectively. Moreover, AVFs with different angles can be categorized based on Dean number ( De) which showed an inverse correlation to WSS range. Thus, creating an AVF with a surgical configuration that results in a low De, representing a sharp bend with large radius of curvature, could result in a hemodynamic condition (high WSS and ΔWSS) that could have adverse effects on the fistula maturation.
Effect of Anastomotic Angle on Pressure Drop in Arteriovenous Fistulae
Authors: Okoye Kenechukwu M. , Rajabi-Jaghargh Ehsan , Banerjee Rupak K.
Published: January 2014

The amount of the blood flow rate to an arteriovenous fistula (AVF) is one of the primary factors that determine the likelihood of maturation. The increase in the flow rate is dependent on the amount of the resistive forces in the AVF which can be evaluated by pressure drop (Δ p). Our group has shown that the surgical configuration of AVF affects the hemodynamics and thus the remodeling within the AVF. Here, our aim is to study the effect of AVF configuration on the induced Δ p. Based on the data collected in our previous in-vivo porcine experiments, idealized models of AVFs with anastomosis angles of 30°, 60°, and 90° were created and numerically solved to find Δ p under steady-state conditions. The Δ p from the idealized models were within the same range as the experimental data (15.31 ± 3.78 mmHg). The highest and lowest Δ p were found to be 14.75 and 6.40 mmHg for the 30° and 90° AVFs, respectively. Moreover, an inverse relationship was found between the Dean number ( De) and Δ p. As De decreased with increasing radius of curvature (from higher anastomotic angles to the lower), the Δ p increased. These data suggest that creating the AVFs in a surgical configuration that results in larger De (lower radius of curvature such as 90° AVF) may achieve higher flow rate due to relatively lower Δ p. In contrast, creation of AVF with lower De which represents a sharp bend with high radius of curvature (30° AVF) could be detrimental to AVF maturation as it results in relatively higher Δ p.
Influence of Hydrophobic Surface Modification of Chitosan Based Methotrexate (MTX) Micro Implants to Treat Intraocular Lymphoma
Authors: Manna Soumyarwit , Augsburger James J. , Correa Zelia M. , Landero Julio A. , Banerjee Rupak K.
Published: January 2014

Primary intraocular lymphoma (PIOL) is a rare form of lymphoma which is encountered in ocular oncology practice. Most preferred treatment has been intravitreal MTX injections which do not have a long lasting chemotherapeutic effect due to rapid elimination of the drug. In this study, chitosan (CS) and polylactic acid (PLA) based intraocular implants are fabricated for different MTX loadings (10%, 25% and 40% w/w). The implants administer a therapeutic dosage of 0.2–2.0 μg/day of MTX over a period of a month. PLA coated CS-MTX implants can be used for sustained release of MTX, thereby improving the treatment of PIOL.
Comparison of Intervertebral Disc Displacements Measured Under Applied Loading With MRI at 3.0T and 9.4T
Authors: Chan Deva D. , Gossett Paull C. , Butz Kent D. , Nauman Eric A. , Neu Corey P.
Published: January 2014

The noninvasive measurement of displacements under applied loading with magnetic resonance imaging (dualMRI) can be implemented on both clinical and high-field research MRI systems. dualMRI synchronizes cyclic loading applied by an MRI-compatible loading device with displacement-encoded MRI [1]. Numerous factors influence the MRI-based measurement of deformation (e.g. displacements and strain) in biomaterials and tissues, including the magnitude and frequency of cyclic loading, the geometry and configuration of the physical environment, and inherent material properties, which are often heterogeneous [2–4].
Tumors Change the Elastic and Viscoelastic Properties of Draining Lymph Node Tissues
Authors: McClain Jacob , Tuell Sara L. , Thomas Susan N.
Published: January 2014

Changes in tissue mechanical properties are often the first indication of malignant disease, with the detection of a stiff lump by a patient. These changes include growth-induced solid stresses, increased matrix stiffness, high fluid pressure, and increased interstitial flow, which in turn enhance fluid flux away from the tumor to downstream lymph nodes (LNs). But in addition to changing the way a tumor feels to a patient, altered tumor tissue mechanics promote cancer cell invasion into lymphatic vessels, allowing their metastatic dissemination to draining LNs. LN swelling and stiffening is another common indicator of tumor growth, and the presence of metastatic cells in the sentinel LN, or tumor draining lymph node (TDLN), is used clinically to stage disease. Recent studies indicate the LN microenvironment determines whether metastatic cancers can spread to the sentinel LNs. Yet despite the known correlation of LN swelling and stiffening with tumorigenesis and the role of the LN microenvironment in metastasis, our understanding of how changes in LN mechanical properties relate to tumor progression, anti-tumor immune response and metastatic colonization of the LN is limited. This lack of a quantitative understanding limits functional analyses of the role of LN mechanics in determining cancer cell colonization of the TDLN, their influence on immune suppression taking place within the TDLN, as well as the development of strategies to mitigate these effects.
Towards a Realistic Model of a Lymphatic Network: Improved Methods of Solution of the Equations for Many Lymphangions in Series
Authors: Bertram Christopher D. , Macaskill Charles , Moore James E.
Published: January 2014

Lymphedema of the arm is a common complication of surgery involving removal of armpit lymph nodes. It is currently incurable, although it can be palliated by massage. Equivalent situations occur following lymphatic interference elsewhere in the body. In the developing world, lymphedema is also caused by elephantiasis.
Numerical Study of Temperature Profile During ADV Enhanced HIFU Thermal Ablation of Tumor
Authors: Xin Ying , Fabiilli Mario , Zhang Aili , Fowlkes Brian , Xu Lisa X.
Published: January 2014

By focusing the highly intensified ultrasound beams to a tiny region, the temperature at the focus could be enhanced to be more than 60°C and ablate the undesired tissues. Due to its non-invasiveness, the treatment (HIFU) is getting more popular.
Directing Stem Cell Fate in 3D Through Cell Inert and Adhesive Diblock Copolymer Domains
Authors: Chirasatitsin Somyot , Viswanathan Priyalakshmi , Battaglia Giuseppe , Engler Adam J.
Published: January 2014

Adhesions are important cell structures required to transduce a variety of chemical and mechanics signals from outside-in and vice versa, all of which regulate cell behaviors, including stem cell differentiation (1). Though most biomaterials are coated with an adhesive ligand to promote adhesion, they do not often have a uniform distribution that does not match the heterogeneously adhesive extracellular matrix (ECM) in vivo (2). We have previously shown that diblock copolymer (DBC) mixtures undergo interface-confined de-mixing to form nanodomins of one copolymer in another (3). Here we demonstrate how diblock copolymer mixtures can be made into foams with nanodomains to better recapitulate native ECM adhesion regions and influence cell adhesion.
Simulating Instrumented Knee Implant Forces With a Simplified Computational Model
Authors: Müller Jacobus H.
Published: January 2014

A simplified computational model is presented with which axial knee implant forces can be estimated. The dataset provided in the IV Grand Challenge to Predict in-vivo Knee Loads [1] is used to assemble a musculoskeletal model, and perform an inverse dynamics analysis. The joint and muscle dynamics recorded during the inverse analysis is then used as target values during a forward dynamics analysis to compute the axial tibiofemoral load.
Effect of Superparamagnetism Nanoparticles on Microwave Rewarming Process of Cryopreserved Tissues
Authors: Wang Tao , Yu Qianfeng , Zhao Gang , Gao Dayong
Published: January 2014

Cryopreservation of tissues would bring great profits for the academic research and the treatments of patients. However, the damage of the tissues during rewarming process greatly limit the clinical applications of cryopreserved tissues, and it has been widely pointed out that such damage is mainly due to devitrification, thermal stress and thermal runaway1,2.
Combining 4D MR Flow Experimental Data and Computational Fluid Dynamics to Study the Neoaorta in Patients With Repaired Transposition of the Great Arteries
Authors: Biglino Giovanni , Cosentino Daria , Castelli Matteo , De Nova Lorenzo , Ntsinjana Hopewell N. , Steeden Jennifer A. , Taylor Andrew M. , Schievano Silvia
Published: January 2014

Transposition of the great arteries (TGA) is a congenital heart disease characterized by abnormal spatial arrangement of the two main vessels, with the aorta arising from the pulmonary valve and the main pulmonary artery arising from the aortic valve. TGA surgical repair with the arterial switch operation (ASO) involves physically repositioning the aorta and the pulmonary artery in their correct anatomical location, as well as separately moving the coronary arteries. Following ASO, decreased aortic distensibility and enlarged aortic root have been observed, together with late complications such as coronary artery obstruction, neoaortic valvar insufficiency, and arrhythmia [1]. Clearly, further knowledge of the hemodynamics in the neoaorta following ASO can be helpful in understanding the physiology of repaired-TGA. We suggest that engineering tools can provide access to such knowledge, both experimentally and computationally. 4D flow data from magnetic resonance (MR) imaging can generate excellent maps of velocity streamlines and — to our knowledge — has never been applied to this clinical problem. In addition, 4D MR flow data gathered in-vitro (hence more reproducible and more stable than in-vivo) can be a resourceful tool for validating a computational fluid dynamics (CFD) model of the same problem. The experimental model, lacking respiration effects and concerns about scanning time, can also be used for exploring the optimal spatial and temporal resolution for improving the quality of the data. Ultimately, we suggest that a synergistic approach (experimental 4D MR flow + CFD study) carried out at a patient-specific level can provide knowledge about the hemodynamics in the neoaorta following ASO. For this purpose, we present two comparisons:

(a) TGA anatomy vs. an age-matched healthy subject

(b) in-vitro vs. in-silico.
Towards a Clinically Applicable Tissue Engineered Vascular Graft
Authors: Sheridan W. S. , Grant O. , Lopez-Noriega A. , Duffy G. P. , Murphy B. P.
Published: January 2014

Decellularized arterial tissue has shown promising use as a scaffold for vascular tissue replacement; similar structural and functional characteristics to the native tissue are maintained and these scaffolds are non-thrombogenic, non immunogenic with the ability to remodel and grow in vivo[1]. However, there still remains a number of limiting factors in clinically translating these scaffolds. Namely, producing a range of geometries to accommodate a large patient cohort within clinically feasible manufacturing times and costs. Furthermore, these scaffolds must be suitable for long term preservation to produce a reasonable shelf life and be capable of undergoing standard sterilization techniques.
The Chink in the Armor of the Mitral Valve Annulus: The Irregular Distribution of Mechanical Properties
Authors: Gunning G. M. , Sheridan W. S. , Murphy B. P.
Published: January 2014

Mitral valve (MV) disease is the most prevalent form of heart valve disease among the US population [1]. MV disease can affect any one of the four components of the mitral valve: chordae tendinae, valve leaflets, papillary muscles or the supporting annulus. In one example of MV disease the annulus can become dilated, and this can subsequently lead to mitral valve insufficiency. Various surgical and catheter based techniques have been developed for repair or replacement of a dysfunctional MV, and many of these procedures involve suturing or anchoring devices directly to the annulus, thus restricting further dilatation of the annulus.
Experimental and Numerical Study of Ascending Aorta Hemodynamics Through 3D Particle Tracking Velocimetry and Computational Fluid Dynamics
Authors: Gülan Utku , Gallo Diego , Ponzini Raffaele , Lüthi Beat , Holzner Markus , Morbiducci Umberto
Published: January 2014

The complex hemodynamics observed in the human aorta make this district a site of election for an in depth investigation of the relationship between fluid structures, transport and pathophysiology. In recent years, the coupling of imaging techniques and computational fluid dynamics (CFD) has been applied to study aortic hemodynamics, because of the possibility to obtain highly resolved blood flow patterns in more and more realistic and fully personalized flow simulations [1]. However, the combination of imaging techniques and computational methods requires some assumptions that might influence the predicted hemodynamic scenario. Thus, computational modeling requires experimental cross-validation. Recently, 4D phase contrast MRI (PCMRI) has been applied in vivo and in vitro to access the velocity field in aorta [2] and to validate numerical results [3]. However, PCMRI usually requires long acquisition times and suffers from low spatial and temporal resolution and a low signal-to-noise ratio. Anemometric techniques have been also applied for in vitro characterization of the fluid dynamics in aortic phantoms. Among them, 3D Particle Tracking Velocimetry (PTV), an optical technique based on imaging of flow tracers successfully used to obtain Lagrangian velocity fields in a wide range of complex and turbulent flows [4], has been very recently applied to characterize fluid structures in the ascending aorta [5].
Improving 3D Cine Phase Contrast MRI Aortic Hemodynamics In Vivo Measurements by Means of an Anisotropic Diffusion Filter
Authors: Tresoldi D. , Morbiducci U. , Gallo D. , Cadioli M. , Ponzini R. , Esposito A. , De Cobelli F. , Rizzo G.
Published: January 2014

3D CINE Phase Contrast Magnetic Resonance Imaging (PCMRI) is considered the technique of election to study in vivo the time varying, complex blood flow structures evolving into arteries [1]. PCMRI allows to obtain a quantitative depiction of the spatial distribution of blood velocities from the acquired phase data and the anatomical image of the district of interest from magnitude data. A major limitation in the application of 3D CINE PCMRI to the clinical practice is the long scan time needed to obtain phase datasets (i.e., blood flow velocities) of sufficient quality for hemodynamic visualizations of time evolving fluid structures or for volumetric flow rates retrospective quantification and analysis. Recently, huge efforts have been done to speed up in vivo acquisitions by implementing/optimizing parallel imaging acquisition schemes as the Sensitivity Encoding (SENSE) [2]. However, the increased reduction factors employed in SENSE scheme to speed up the acquisition lead to acquired PCMRI images affected by marked noise levels, with detrimental effects on measured velocity vector fields. A solution could be offered by the application of an Anisotropic Diffusion Filter (ADF) [3]. Anisotropic filtering is already known for its ability in reducing noise without adding blurring effects, thus preserving fine image details, and it is applied here for the first time to PCMRI data. In this work we propose the application of an ADF strategy to 3D cine PCMRI data of the thoracic aorta obtained with SENSE parallel imaging. The effectiveness of anisotropic filtering in improving image quality for the in vivo hemodynamic characterization of the aorta has been investigated on PCMRI studies acquired with different SENSE reduction factors. The final aim is to denoise and regularize 3D cine velocity maps, preserving, in the meantime, the vessel anatomical contours. This approach could allow to obtain the full 3D characterization of the aortic hemodynamics in acquisition times which are acceptable in the clinical practice.
Nano-Scale and Micro-Scale Substrate Architectures Direct Collagen Alignment in Tendon Neo-Tissue Formation
Authors: Gilchrist Christopher L. , Ruch David S. , Little Dianne , Guilak Farshid
Published: January 2014

Biomaterial scaffolds that present defined microenvironmental cues (e.g., nano-topography) to cells have shown promise for a variety of tissue engineering applications. However, the specific cues best suited for promoting the formation of aligned, fibrous tissues such as tendon are not fully understood. In this study, we utilize a micro-photopatterning (μPP) model system to precisely arrange scaffold-mimicking microenvironmental cues and investigate their role in the formation of tendon-like neo-tissues. Our data show that scaffold architectural features at both nano- and micro-length scales may be important parameters for directing tendon-like cell organization and the formation of aligned, fibrillar collagen.
Development of Framework to Examine the Focal Association Between Wall Shear Stress and Coronary Artery Disease Progression in the Clinical Setting
Authors: Timmins Lucas H. , Molony David S. , Eshtehardi Parham , McDaniel Michael C. , Oshinski John N. , Samady Habib , Giddens Don P.
Published: January 2014

Natural history data on clinical coronary artery disease (CAD) indicates that there is a critical need to prospectively identify rapidly progressing and vulnerable coronary lesions that may cause potentially fatal acute coronary events [1]. Recent prospective clinical investigations have evaluated the value of wall shear stress (WSS) as a prognostic marker for identifying rapidly progressing coronary lesions [2,3]. Data indicate that low WSS is associated with significant plaque progression, while regions of high WSS are associated with plaque regression and phenotypic transformation towards a more vulnerable lesion. While these studies provided unprecedented data on the role of hemodynamic-induced mechanical forces in lesion dynamics, they were limited by a lack of focal understanding of the association between WSS and plaque progression. Specifically, despite the understanding that WSS and plaque progression are heterogeneous around the artery’s circumference, in each image slice WSS values were spatially averaged around the circumference and correlated with average values for changes in virtual histology-intravascular ultrasound (VH-IVUS) defined plaque constituent areas.
A Custom Image-Based Analysis Tool for Quantifying Elastin and Collagen Fiber Micro-Architecture in the Wall of the Human Aorta From Multi-Photon Microscopy Images
Authors: Koch Ryan G. , Tsamis Alkiviadis , D’Amore Antonio , Wagner William R. , Vorp David A.
Published: January 2014

The two primary load-bearing components of the connective fiber micro-architecture of aorta are the proteins elastin and collagen. The structure of elastin and collagen fibers is important to support the proper function of the aorta, and alteration of the quantity and/or arrangement of these fibers can lead to mechanical and functional changes associated with aortic disease. Therefore, an adequate quantification of the micro-architecture of elastin and collagen fibers in the aortic wall would provide insight into the influence of micro-architecture on the biomechanical response of the aorta in health and disease.
Visualizing Chondrocyte Mechanotransduction in 3D
Authors: Wan Qiaoqiao , Cho Eunhye , Park Seungman , Han Bumsoo , Yokota Hiroki , Na Sungsoo
Published: January 2014

Chondrocytes are the only cell type present in the articular cartilage and their response to mechanical stimuli influences the maintenance and remodeling of the cartilage. Numerous studies have shown that the balance between anabolic and catabolic responses of the chondrocytes to mechanical loading is dependent on the loading intensities (reviewed in ref. [1]). Moderate, physiological loading, for instance, increases synthetic activity of the extracellular matrix (ECM) such as collagen type II, aggrecan, and proteoglycan, while decreasing the catabolic activity of degradative enzymes such as matrix metalloproteinases (MMPs) and ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) [2,3]. In contrast to moderate loading, static or high-intensity loading has been shown to degrade the cartilage resulting from inhibition of matrix synthesis and up-regulation of catabolic activities [3,4]. Therefore, the importance of these load-dependent signaling pathways involved in the maintenance and remodeling of the cartilage is widely accepted. However, the underlying mechanisms as to how varying magnitudes of mechanical stimuli trigger differential signaling activities that consequently lead to selective gene expression are not clear. FAK and Src are considered to be the main mechanotransduction signaling proteins at the cell-ECM adhesion sites and their activities influence various structural and signaling changes within the cell, including cytoskeletal organization, migration, proliferation, differentiation, and survival [5]. Accumulating evidence has shown that Src and FAK play crucial roles in regulating cartilage maintenance and degeneration and their activation stimulates matrix catabolic genes and activity [6,7]. Rho family GTPases such as RhoA and Rac1 play critical roles in fundamental processes including morphogenesis, polarity, movement, and cell division [8]. They also contribute to cartilage development and degradation [9,10]. Despite these studies, much remains to be elucidated on how load-induced Src and FAK participate in chondrocyte functions, and how their interactions are linked and regulated in connection to the activities of RhoA and Rac1 under different loading conditions. In this study, we use fluorescence resonance energy transfer (FRET)-based biosensors to monitor activities of Src and FAK as well as individual GTPases and evaluate the potential linkage of a network of these signaling molecules under different loading conditions.
Sudden Death in Coronary Artery Disease are Associated With High 3D Critical Plaque Wall Stress: A 3D Multi-Patient FSI Study Based on Ex Vivo MRI of Coronary Plaques
Authors: Huang Xueying , Yang Chun , Zheng Jie , Bach Richard , Muccigrosso David , Woodard Pamela K. , Tang Dalin
Published: January 2014

Atherosclerotic plaque rupture is the primary cause of cardiovascular clinical events such as heart attack and stroke. It is commonly believed that plaque rupture may be linked to critical mechanical conditions. Image-based computational models of vulnerable plaques have been introduced seeking critical mechanical indicators which may be used to identify potential sites of rupture [1–5]. A recent study by Tang et al. [4] using in vivo MRI-based 3D fluid-structure interaction (FSI) models for human carotid plaques with and without rupture reported that higher critical plaque wall stress (CPWS) values were associated with plaques with rupture, compared to those without rupture. However, existing computational plaque models are mostly for carotid plaques based on MRI data. Comparable similar studies for coronary plaques are lacking in the current literature. In this study, 3D computational multi-component models with FSI were constructed to identified 3D critical plaque wall stress, critical flow shear stress (CFSS) based on ex vivo MRI data of coronary plaques acquired from 10 patients. The patients were split into 2 groups: patients died in carotid artery disease (CAD, Group 1, 6 patients) and non CAD (Group 2, 4 patients). The possible link between CPWS and death in CAD was investigated by comparing the CPWS values from the two groups.
A Novel Perfusion Bioreactor for 3D Cell Culture in Microgravity Conditions
Authors: Isu Giuseppe , Massai Diana , Cerino Giulia , Gallo Diego , Bignardi Cristina , Audenino Alberto , Morbiducci Umberto
Published: January 2014

Cell suspension culture methods based on the generation of microgravity environment are widely used in regenerative medicine for (1) the production of native-like three-dimensional (3D) cell aggregates and engineered tissues [1,2,3], for (2) low cost scalable cell expansion and long-term cell viability maintenance [4,5], and for (3) guiding differentiation of stem cells (SCs) [6]. The generation of a microgravity environment for 3D cell cultures, mimicking the native environment, promotes spatial freedom, cell growth, cell-cell interaction and improves mass transfer and cell exposure to nutrients. Nowadays, microgravity cell cultures are obtained by using stirred or rotating bioreactors, but both devices suffer from limitations: stirring bioreactors generate non-physiological shear stresses, which could damage cultured cells, interfere with SC pluripotency, and limit reproducibility of the culture process; rotating bioreactors are expensive devices due to the complex technological solutions adopted for obtaining rotation [5].
Rheology Effects on Mucus Plug Rupture
Authors: Hu Yingying , Bian Shiyao , Filoche Marcel , Grotberg John C. , Takayama Shuichi , Grotberg James B.
Published: January 2014

Human respiratory mucus has non-Newtonian rheological properties of viscoelasticity, shear-thinning and yield stress. They play significant roles in mucus clearance by ciliary motion as well as cough [5,7,9]. Mucus is hypersecreted in such lung diseases as cystic fibrosis and asthma. Mucus hypersecretion damages mucus clearance mechanism [6], and more likely causes plugs to block partial or total airways [4].
Cervical Collagen Network Remodeling in Normal and Disrupted Parturition Mouse Models
Authors: Yoshida Kyoko , Reeves Claire , Kim MiJung , Kitajewski Jan , Vink Joy , Wapner Ronald , Paik David , Myers Kristin
Published: January 2014

The cervix plays an important role in pregnancy as a mechanical barrier to prevent preterm birth (PTB). The material strength of the cervix can be attributed to its extracellular matrix (ECM), a network of cross-linked collagens (types I and III) embedded within a viscous matrix of glycosaminoglycans (GAG). GAGs are negatively charged polysaccharides that provide a fixed charge density (FCD) within the tissue to maintain hydration. Throughout gestation, the ECM of the cervix undergoes a remodeling process characterized by three stages: gradual softening in early pregnancy, a rapid increase in tissue distensibility termed ripening in late pregnancy, and repair at post partum 1. As the cervix softens and ripens, mature collagen cross-links break down while GAG content increases 2,3. Previous research has shown that these changes in collagen and GAGs correlate to a mechanically softer cervix at term 4.
Abdominal Aortic Aneurysm Rupture Risk Assessment Exploiting Dynamic (4D) CT Based Wall Motion Data and Finite Element Analysis
Authors: Metaxa Eleni , Vavourakis Vasileios , Kontopodis Nikolaos , Pagonidis Konstantinos , Ioannou Christos V. , Papaharilaou Yannis
Published: January 2014

Abdominal aortic aneurysm (AAA) disease is primarily a degenerative process, where rupture occurs when stress exerted on the aortic wall exceeds its failure strength. Therefore, knowledge of both the wall stress distribution and the mechanical properties of the AAA wall is required for patient specific rupture risk estimation.
The Changing Depth Dependant Properties of Articular Cartilage During Postnatal Development
Authors: Gannon A. R. , Kelly D. J.
Published: January 2014

During skeletal development and maturation compositional and architectural changes occur in articular cartilage. Specifically, the collagen architecture changes from a predominantly isotropic structure in immature articular cartilage to a mature arcade-like zonal structure first described by Benninghoff (1925)1,2,3. The goal of this study was to elucidate how the structure and composition of articular cartilage change during postnatal development and maturation and to relate this to the mechanical properties of the tissue, focusing in particular on how the key superficial region of the tissue adapts with age. To this end articular cartilage from a variety of age groups (one month old-immature, one year old-skeletally mature and three years old-fully mature) were subjected to increasing levels of strain. Local levels of deformation in the tissue were determined by fluorescently labelling and imaging cells that acted as fiducial markers. This enabled the local levels of strain and hence tissue mechanical properties to be determined with age and skeletal maturity.
Effects of Chondroadherin on Cartilage Nanostructure and Biomechanics via Murine Model
Authors: Batista Michael , Nia Hadi T. , Cox Karen , Ortiz Christine , Grodzinsky Alan J. , Heinegård Dick , Han Lin
Published: January 2014

While small leucine rich proteins/proteoglycans (SLRPs) are present in very low concentrations in the extracellular matrix (ECM), they have been shown to be critical determinants of the proper ECM assembly and function in connective tissues [1] including bone [2], cornea [3], and cartilage [4]. However, their direct and indirect roles in matrix biomechanics and the potential for osteoarthritis-related dysfunction of cartilage remain unclear. With the advent of new high resolution nanotechnological tools, the direct quantification of cartilage biomechanical properties using murine models can provide important insights into how secondary ECM molecules, such as SLRPs, affect the function and pathology of cartilage [5]. Previous nanoindentation studies of murine cartilage have assessed the effects of maturation and osteoarthritis-like degradation of cartilage on its biomechanical properties [6, 7]. Recently, murine models have received increased attention because of the availability of specific gene-knockout and gene alteration technologies [8]. For example, chondroadherin (CHAD) is a non-collagenous small leucine-rich proteoglycan (SLRP) with α-helix and β-sheet secondary structure, spatially localized in the territorial matrix (MW = 38 kDa) [9]. In articular cartilage, CHAD is distributed non-uniformly with depth [10], and binds to type II collagen and the α2β1 integrin and is hypothesized to function in the communication between chondrocytes and their surrounding matrix, as well as in the regulation of collagen fibril assembly [11, 12] (Fig. 1). The objective of the present study is to explore the role of CHAD and its depletion on the structure and nanomechanical properties of both superficial and middle/deep zone cartilage. The current methods thereby enabled depth-dependent analysis of cartilage nanostructure and dynamic energy-dissipative mechanisms.
Fabrication of Hybrid Cell-Microbead Constructs Using Laser Direct-Write of Alginate Microbeads and Adherent Breast Cancer Cells
Authors: Dias Andrew D. , Kingsley David M. , Chrisey Douglas B. , Corr David T.
Published: January 2014

Microbeads are becoming popular tools in tissue engineering as 3D microstructure hydrogels. The gel nature of microbeads enables them to sequester soluble factors and mammalian cells, and their high surface area-to-volume ratio allows diffusion between the bead and the environment [1,2]. Microbeads are thus good systems for drug delivery and can serve as 3D microenvironments for cells. To fully maximize their potential as delivery systems and microenvironments, it is highly desirable to create spatially-precise hybrid cultures of microbeads and mammalian cells. Precise placement of microbeads in proximity to patterned cells will allow the study of spatial cellular interactions, paracrine signaling, and drug delivery.
Abdominal Aortic Stent Graft Mechanics: Sizing Them Up
Authors: De Bock S. , Iannaccone F. , De Beule M. , Vermassen F. , Segers P. , Verhegghe B.
Published: January 2014

An abdominal aortic aneurysm (AAA) of the aorta is a local widening of the aorta in a region between the renal arteries and the aortic bifurcation. The disease impacts the structural integrity of the AAA wall, weakening the tissue and predisposing it to rupture. Preventive treatment of the disease is often performed minimally invasive with endovascular repair by stent graft deployment, as an alternative to open surgical repair. During endovascular aneurysm repair, a metallic stent, covered with a polymer membrane is first crimped and mounted onto the delivery system and inserted through the iliac artery. It is advanced to the AAA region, and expanded to cover the weakened, ballooning aorta. The technique has excellent clinical outcome, yet it is still associated with long term problems such as migration, a downward displacement of the device, and endoleakage, with blood reentering and pressurizing the aneurismal sack.
Is Presbyopia Caused by Lens Growth-Induced Residual Stresses?
Authors: Reilly Matthew A.
Published: January 2014

Prevailing wisdom holds that increasing lens stiffness causes presbyopia. Treatments for presbyopia have therefore focused on altering the mechanical properties of the ocular lens. The present work shows an age-related decline in accommodation amplitude may be predicted without invoking changes in lens stiffness.
Cerebrospinal Fluid Dynamics in the Cervical Spine: Importance of Fine Anatomical Structures
Authors: Pahlavian S. H. , Yiallourou T. I. , Tubbs R. S. , Bunck A. , Goodin M. , Loth F. , Raisee M. , Martin B. A.
Published: January 2014

Fine anatomical structures, including nerve roots and denticulate ligaments, can significantly influence cerebrospinal fluid (CSF) dynamics inside the spinal subarachnoid space (SSS). In this study, we completed computational fluid dynamics (CFD) simulations based on subject specific geometries of the cervical spine with and without idealized fine structures (nerve roots and denticulate ligaments, NRDL). The results show that NRDL had a significant impact on CSF dynamics in terms of velocity distribution, flow streamlines, bidirectional nature of the flow and the pressure drop.
Uptake of Soluble Gases in the Entire Respiratory Systems of Rats and Humans Using Transient CFD/PBPK Models
Authors: Kabilan S. , Kuprat A. , Einstein D. , Carson J. , Jacob R. , Minard K. , Corley R.
Published: January 2014

With the advancement of experimental and computational techniques, three-dimensional (3D) computational fluid dynamics (CFD) airflow models of the respiratory system have increasingly been used to evaluate aerosol deposition, gas exchange and airflow characteristics under various physiological and/or disease conditions. One specific application that is emerging in the field of toxicology is assessing the risk for exposure to highly reactive, water-soluble gases and vapors including formaldehyde, acetaldehyde, hydrogen sulfide, and acrolein by coupling CFD models of nasal airways of rats and humans to physiological based pharmacokinetic (PBPK) models.