bluuebunny/crossref_metadata_2025 huggingface dataset:
A Two-Point Conductivity Approach to Measuring Fixed Charge Density in Intervertebral Disc Tissue
Authors: Jackson Alicia R. , Yuan Tai-Yi , Huang Chun-Yuh , Gu Wei Yong
Published: July 2013

Low back pain, a major socio-economic concern in the United States, is believed to result from degeneration of the intervertebral disc (IVD) of the spine [1]. The IVD is characterized as a charged, hydrated soft tissue made up of a central nucleus pulposus (NP) surrounded by the layered annulus fibrosus (AF). The negatively-charged nature of the disc derives from the charged groups attached to the glycosaminoglycan (GAG) molecules found on proteoglycans (PG) in the extracellular matrix of the disc. The fixed charge density (FCD) is a measure of the number of negative charges attached to the disc matrix per unit volume. FCD is important to disc function, both mechanically (i.e., swelling pressure) and in terms of transport through the disc [2].
Ventricular Wall Stress and Pump Function of Ventricular Septal Defect of Congenital Heart Defects
Authors: Jhun Choon-Sik , Ratcliffe Mark B. , Guccione Julius M.
Published: July 2013

About 36,000 infants are born each year with a congenital heart defect (CHD) and charges for treatment surpass $2.2 billion for inpatient surgery alone. Of many different types of CHDs, ventricular septal defect (VSD) is the most common class (∼1/3 of CHDs) of heart deformity present at birth. Though many close spontaneously and rarely require treatment, VSD still accounts for ∼15% of defects requiring an invasive procedure within the first year of life [1]. Generally, the ventricular performance is indexed by geometry, shape, diastolic and systolic function, and myocardial contractility [2]. Ejection fraction (EF) and end-systolic (ES) wall stress also used to assess the ventricular function [3–5]. Ratcliffe and Guy suggested that the assessment of LV function focusing on indices of systolic function, such as EF and contractility (EES), is misleading because the shift of end-systolic pressure-volume relationship (ESPVR) and increase/decrease in EES and coincident shift of end-diastolic pressure-volume relationship (EDPVR) may result in pseudo increase/decrease of EF even though there may not be any significant change in true LV function (i.e., Starling relationship) [6]. Though Sagawa and associates proposed the ESPVR as a reliable index of intrinsic systolic function [7], it requires derivation of the pressure-volume relationship at different loading conditions by using a noninotropic vasoconstrictor or vasodilator. This may consequently enforce a significant burden on infants with a failing heart. Moreover, irreversible complication of muscle structure can be generated [8–10]. Thus, rigorous quantification of the pump function associated with mechanics has been hindered especially for infants.
A Structure-Based Model of Arterial Remodeling in Response to Sustained Hypertension
Authors: Tsamis Alkiviadis , Stergiopulos Nikos , Rachev Alexander
Published: July 2013

Pressure-induced remodeling of arteries is an adaptive process, which restores the magnitude of media tensile stress and intimal shear stress to their baseline values under normotensive conditions [1]. Revealing the role that mechanical factors play in arterial adaptation is important for understanding the normal arterial function as well as the pathogenesis of various arterial diseases.
The Effect of Collagen Fiber Directional Distribution on the Mechanical Response of the Vascular Wall
Authors: Rezakhaniha Rana , Stergiopulos Nikos
Published: July 2013

Constitutive equations reflecting well the microstructure are fundamental for the detailed stress analysis of the arterial tissue. Vascular tissue is an inhomogeneous and incompressible material which undergoes large deformations and shows highly anisotropic nonlinear behavior. These properties make strain energy functions (SEFs) a suitable tool to derive constitutive equations. Structural constitutive models try to integrate the histological and morphological characteristics of the tissue by introducing parameters with physical meaning, such as the fraction of each wall constituent, the elastic properties of single elastin or collagen fibers or the angle of collagen fibers.
Bacterial Cellulose: A Potential Vascular Graft and Tissue Engineering Scaffold
Authors: Zahedmanesh Houman , Gatenholm Paul , Lally Caitríona
Published: July 2013

Cardiovascular disease is the major cause of morbidity and mortality in the adult population and treatment of many of the patients struggling with such diseases requires surgical interventions involving replacement of diseased arteries. Although currently it is possible to replace large arteries with synthetic grafts made of materials such as polyester and expanded polytetrafluoroethylene (ePTFE) [1], these materials may not be used as small size grafts given their thrombogenicity and propensity for intimal hyperplasia [2]. As a result, development of suitable grafts as a substitute for small size arteries (< 6mm in diameter) such as the coronary arteries remains a daunting challenge.
Primary Design of a Shape Memory Alloy Expandable Insert to Enhance Pedicle Screw Performance
Authors: Tabesh Maiid , Elahinia Mohammad
Published: July 2013

Shape Memory Alloys, such as Nickel Titanium, undergo a phase transformation in their crystalline structure when transformed from Austenite into Martensite. This inherent phase transformation is the basis for the unique properties of shape memory and superelasticity. Shape memory is attributed to the recovery of large mechanically induced deformations upon raising the temperature upto a specific level (Af). The superelasticity is the ability of the material, at a temperature above Austenite start Af, to recover mechanical deformations upon unloading. Thanks to superelasticity, shape memory effect, high damping capacity, corrosion resistance and biocompatibility, NiTi SMA alloys gain researchers attention for implementation in biomedical fields for the past 40 years [1].
Internal Pressure in Human Meniscal Attachments Subjected to Physiological Loading
Authors: Villegas Diego F. , Miller Emily J. , Morrow Duane , Kaufman Kenton R. , Haut Donahue Tammy L.
Published: July 2013

Meniscal attachments serve to anchor and transfer loads from menisci to the tibia. These ligamentous tissues are composed of collagen fibers, elastin, ground substance and water. Ligaments have a time- and history-dependent viscoelastic behavior due in part to the interaction of the water and the ground substance [1]. The movement of water within ligamentous tissue is limited because of charged proteoglycan molecules. It has been shown that some exudation of water is present during cyclic loading of ligamentous tissue [2]. The movement and its inhibition could lead to changes of pressure within the meniscal attachments. Therefore, the purpose of this study was to quantify the internal pressure in human meniscal attachments subjected to physiological loading. Since it is thought that the posterior attachment is subjected to both tension and compression, while the anterior attachment is primarily subjected to tension [3–5], we hypothesized that the attachments mechanical environment is dictated by the external loads, and hence, the posterior attachment would elicit higher pressures.
Stiffness Comparisons Between Adventitia, Media and Full Thickness Specimens From Human Atherosclerotic Carotid Arteries
Authors: Hoffman Allen H. , Teng Zhongzhao , Mui Calvin , Zheng Jie , Woodard Pamela K. , Tang Dalin
Published: July 2013

Arteries display highly nonlinear, anisotropic material behavior and can be considered to be a layered composite of fiber oriented materials composed of three layers: intima, media and adventitia. The intima does not affect the material properties of the artery. Thus, the mechanical properties of an artery result from the combined interaction of the media and adventitia with each layer displaying different material properties. It has been widely accepted that atherosclerosis changes the material properties of the arterial wall. However, little experimental data exists relating the properties of the media and adventitia of atherosclerotic vessels to the overall properties of the artery. Knowledge of the properties of human atherosclerotic tissues is essential for an improved understanding the effects of atherosclerosis and also for creating more accurate computational models for predicting the effects of the disease [1]. A prior study of bovine carotid arteries determined the properties of the adventitia and media using a deductive method [2]. This paper focuses on directly measuring and comparing the stiffness of paired samples of adventitia, media and full thickness specimens from human atherosclerotic carotid arteries.
The Inhomogeneous Mechanical Properties of the Pericellular Matrix of Articular Cartilage Measured In Situ by Atomic Force Microscopy
Authors: Wilusz Rebecca E. , Darling Eric M. , Bolognesi Michael P. , Zauscher Stefan , Guilak Farshid
Published: July 2013

Articular cartilage is the connective tissue that lines the articulating surfaces of diarthrodial joints, providing a low-friction, load-bearing surface during joint motion. Articular cartilage comprises of a single cell type, the chondrocyte, embedded within an extensive extracellular matrix (ECM). Each chondrocyte is surrounded by a narrow region called the pericellular matrix (PCM) that is distinct from the ECM in both its biochemical composition [1] and biomechanical properties [2]. While multiple techniques have been used to measure the mechanical properties of the PCM, including micropipette aspiration of isolated chondrons [2], these studies required mechanical or enzymatic extraction of the chondrocyte and surrounding PCM (i.e., the “chondron” [1]) from the cartilage, and the influence of this isolation process on PCM properties is unknown. Atomic force microscopy (AFM) provides a high resolution form of nano- and microindentation approaches that can be used to measure local mechanical properties in situ [3,4]. The objective of this study was to use AFM to quantify the biomechanical properties of the ECM and PCM of human articular cartilage in situ.
Modeling the Matrix of Articular Cartilage Using a Continuous Fiber Angular Distribution Predicts Many Observed Phenomena
Authors: Ateshian Gerard A. , Rajan Vikram , Chahine Nadeen O. , Guterl Clare Canal , Hung Clark T.
Published: July 2013

A number of theoretical frameworks embodying the disparity between tensile and compressive properties of cartilage have been proposed, accounting for the collagen fibers implicitly [1,2] or explicitly [3–5]. These models generally propose discrete fiber families to describe the collagen matrix. They are able to capture the most salient features of the cartilage mechanical response, namely, the tension-compression nonlinearity of the stress-strain curve [6].
Validation of a Person Specific 1D Model of the Systemic Arterial Tree
Authors: Reymond Philippe , Bohraus Yvette , Perren Fabienne , Stergiopulos Nikos
Published: July 2013

The aim of this study is to validate a person-specific distributed model of the main systemic arterial tree. This model is built and validated with non-invasive measurements on the same person, leading therefore to a coherent set of physiological data. One-dimensional (1D) models have been used for more than 30 years to predict or analyze pressure and flow in the arterial tree (Avolio [1], Stergiopulos et al [2], Westerhof et al [3]), demonstrating their aptitude of modeling wave propagation, however, they have never being validated using in vivo measurements. A quantitative validation was performed in vitro in an elastic tube network dimensioned to resemble the human arterial tree by Matthys et al. [4]. The results were supportive of the 1D model’s capacity to yield good predictions, however, neither the form of the waves nor the elastic properties of the in vitro tube network were matching faithfully their physiological counterparts, so the interest to quantitatively validate the 1D model in vivo remained.
CFD-Aided Design of a Dynamic Culture System for the Co-Culture of Adherent and Non-Adherent Cells
Authors: Cantini Marco , Fiore Gianfranco B. , Redaelli Alberto , Soncini Monica
Published: July 2013

Haematopoietic stem cell (HSC) transplantation has been widely used to treat patients that have undergone high-dose chemotherapy or radiotherapy for haematological or non-haematological malignancies, and is currently investigated for the treatment of several other pathologic conditions. Nevertheless, present and expected clinical applications are hindered by the shortage of cells available for transplantation. Hence, many researchers have attempted to achieve an in vitro expansion of HSCs, using different experimental set-ups and approaches, which range from traditional static monolayer cultures to three-dimensional (3D) dynamic systems. Specifically, several bioreactor systems have been proposed, including perfusion chambers, stirred, rotating, hollow fiber, and packed bed reactors [1]. Taken together, literature studies suggest that a dynamic 3D culture system may provide superior expansion of HSCs.
Airflow in the Human Nasal Cavity: An Inter-Subject Comparison
Authors: Taylor Donal J. , Doorly Denis J. , Schroter Robert C.
Published: July 2013

The human nose is a remarkably complicated biological conduit that plays a significant, perpetual role in respiratory defense and olfaction. It is not a passive organ and has evolved to balance many conflicting requirements, while processing 10,000 litres of inspired air in a typical day [1]. The highly vascularised nasal mucosa heats and humidifies adjacent airflow, whilst the nasal mucosa collects nearly all particles over 5 μm diameter and approximately 50% of those between 2–4 μm [1]. Furthermore, the nasal airways house the olfactory apparatus, which enables humans to sense (smell) the external environment. The research presented here incorporates Computational Fluid Dynamics (CFD) in conjunction with experimental optical measurement techniques to resolve the patterns of flow within the nasal airways of two healthy subjects. This abstract details the experimental and computational methodologies used to simulate constant inspiration at a rate of 100 ml.s−1, which is representative of quiet restful breathing. The results presented focus on a comparison of the upper airway flow distributions in both subjects.
Finite Element Predictions of Cartilage Mechanics in Normal Hips
Authors: Harris Michael D. , Anderson Andrew E. , Ellis Benjamin J. , Maas Steve A. , Joshi Sarang C. , Peters Christopher L. , Glaunes Joan A. , Weiss Jeffrey A.
Published: July 2013

Abnormal loading of hip joint articular cartilage is thought to be the primary cause of hip osteoarthritis (OA). This can occur due to anatomical pathologies such as dysplasia and femoroacetabular impingement (FAI). Computational methods (e.g., the finite element (FE) method) may be able to predict patient-specific cartilage mechanics using non- or minimally invasive methods. We have shown that a subject-specific finite element model can predict contact pressures that agree well with experimental data [1]. As a necessary precursor to analyzing the contact mechanics of pathological hips, the objective of this study was to quantify variations in the magnitude and spatial distribution of cartilage contact pressures in normal hips using FE models of human volunteers with no history of hip disease.
Transmural Flow Bioreactor for Vascular Tissue Engineering
Authors: Bjork Jason W. , Tranquillo Robert T.
Published: July 2013

There is a clear need for tissue-engineered arteries for procedures such as coronary artery bypass grafts. In nearly one-third of cases, there is no healthy supply of autologous vasculature for grafting due to preexisting conditions or previous surgical intervention [1]. Studies in our lab have focused on fabricating a “media equivalent” or ME as a precursor to a fully endothelialized bioartificial artery. Vascular grafts cultured in vitro are often done so under static conditions with some degree of mechanical stimulation [2, 3] and are thus likely to operate in a diffusional transport regime for nutrient delivery and metabolite removal. In this study, we present an analysis of dissolved oxygen (DO) transport limitations in a statically cultured ME and bioreactor designs that improve transport by controlled perfusion of medium axially and transmurally through the engineered tissue with the goal of achieving stronger and more uniform tissue.
A Patient Based Approach for Fluid Structure Interaction in Ruptured Abdominal Aortic Aneurysms
Authors: Xenos Michalis , Rambhia Suraj , Alemu Yared , Einav Shmuel , Ricotta John J. , Labropoulos Nicos , Tassiopoulos Apostolos , Bluestein Danny
Published: July 2013

Fluid structure interaction (FSI) simulations were conducted to assess the risk of rupture in reconstructed AAA from patients who had contained ruptured AAAs. The goal was to test to ability of our FSI methodology to predict the location of rupture, by correlating the high wall stress regions with the actual rupture location. We also present a parametric study in which the relationship of iliac bifurcation angle and the role of embedded calcifications were studied in respect to the aneurismal wall stress.

The patient specific AAA FSI simulations were carried out with advanced constitutive material models of the various components of AAA, including models that describe the wall anisotropy, structural strength based on collagen fibers orientation within the arterial wall, AAA intraluminal thrombus (ILT), and embedded calcifications. The anisotropic material model used to describe the wall properties closely correlated with experimental results of AAA specimens [1].

The results demonstrate that the region of rupture can be predicted by the region of the highest wall stress distribution. Embedded wall calcifications increase the local wall stress surrounding calcified spots, and eventually increases the risk of rupture. FSI results in streamlined AAA geometries show that the maximum stress on the aneurismal wall increases as the iliac bifurcation angle increases.
Vascular Remodeling of Arteriovenous Fistula
Authors: Krishnamoorthy Mahesh K. , Roy-Chaudhury Prabir , Wang Yang , Holland Christy K. , Rigger David , Choe Ann , Banerjee Rupak K.
Published: July 2013

Arteriovenous (AV) fistula failure is a major clinical problem for the 350,000 patients currently on hemodialysis in the United States. The reasons for this failure are mainly attributed to venous stenosis due to neointimal hyperplasia together with a possible failure of vascular dilatation [1]. Despite the magnitude of the clinical problem, there are currently no effective therapies for AV fistula failure. We believe that this is due to a lack of knowledge about the mechanisms involved in both neointimal hyperplasia and vascular dilatation in the specific context of AV fistulae.
Finite Element Modeling of the Connective Tissues of the Optic Nerve Head in Bilaterally Normal Monkeys
Authors: Roberts Michael D. , Sigal Ian A. , Liang Yi , Burgoyne Claude F. , Downs J. Crawford
Published: July 2013

Glaucoma is a chronic and progressive optic neuropathy that gradually narrows the field of vision and can culminate in blindness. Despite extensive and prolonged research efforts, the mechanisms that initiate and fuel progression of the disease are not well understood. However, reduction of intraocular pressure (IOP) has been shown to be an effective therapy for slowing glaucomatous progression, although the specific role of IOP in the disease is not well understood.
A Semi-3D Real-Time Imaging Technique for Measuring Bone Cell Deformation Under Fluid Flow
Authors: Baik Andrew D. , Lu X. Lucas , Huo Bo , Liu X. Sherry , Dong Cheng , Guo X. Edward
Published: July 2013

Bone cells respond to fluid shear loading by activating various biochemical pathways, mediating a dynamic process of bone formation and resorption. The whole-cell volume dilatation [1] and regional deformation of intracellular structures [2] may be able to directly activate and modulate relevant biochemical pathways. Therefore, understanding how bone cells deform under fluid flow can help elucidate the fundamental mechanisms by which mechanical stimuli are able to initiate biochemical responses. Most studies on cell deformation have focused only on cell deformation in the plane parallel to the substrate surface. Height-dependent cell deformation has not been well characterized even though it may contribute greatly to mechanotransduction mechanisms. Traditional techniques to obtain this additional height information of a cell-body, such as confocal and deconvolution microscopy, are inherently limited by the timescale under which the deformational information can be visualized. Previous studies have investigated cell adhesion to substrate under flow using a single view side-view imaging technique [3, 4]. In this study, we present a novel technique that is able to image a single cell simultaneously in two orthogonal planes to obtain real-time images of a cell at a millisecond timescale. Thus, the objectives of this study were to: (1) develop an imaging technique to visualize the depth-directional information of a cell simultaneously with the traditional 2D view; (2) map out the strain fields of the cell by image analysis; and (3) investigate the viscoelastic behavior of osteoblasts under steady fluid flow.
Comparison of Methods for RCR Component Selection From Computational Model Impedance Spectra
Authors: Perkins Lucy E. , Steele Brooke N.
Published: July 2013

Vascular impedance represents the opposition to periodic blood flow though a network of vessels and is a good choice for use as a boundary condition for hemodynamic modeling. Vascular impedance can be computed using electrical analogs, such as two or three element Windkessel models, or computed from geometry using Womersley’s input impedance equations [3]. The challenges associated with using electrical analogs are the need for experimental data to determine appropriate component values and in determining an appropriate methodology to fit the experimental data to the simplified model. The challenges associated with using a geometry-based method are the necessity of knowing the geometry being modeled and the requirement of a periodic solution. While Windkessel models are routinely used in analyses, little detail is provided as to how these R and C parameters are extracted from the impedance spectra. Therefore, we examine the relative importance of matching different characteristics of impedance spectra to the resulting pressure and flow relationships.
Endothelial-Fibroblast Interactions in Angiogenesis and Matrix Remodeling
Authors: Hurley Jennifer R. , Narmoneva Daria A.
Published: July 2013

Revascularization is critical for successful regeneration of ischemic cardiac tissue after injury. To achieve revascularization in engineered cardiac grafts, it is necessary to understand the interactions between major cardiac cell types. The importance of cardiomyocyte-endothelial interactions in angiogenesis is well documented [1]; however, less is known about interactions between endothelial and stromal cells, fibroblasts in particular. Studies indicate that during capillary assembly, fibroblasts (FBs) provide chemical signaling via growth factor expression and endothelial activation and proliferation [2]. In addition, fibroblasts deposit extracellular matrix (ECM) proteins [3] and also play a role in matrix remodeling. The objective of our study was to further investigate the role of endothelial-fibroblast interactions in angiogenesis with a focus on FB regulation of the extracellular mechanical environment. We and others have recently shown that self-assembling peptide nanoscaffold is a promising material for cardiac tissue regeneration, enhancing angiogenesis in vitro and promoting tissue neovascularization in vivo [1, 4–5]. An important advantage of this nanoscaffold is the ability to control its material properties, such as stiffness and rate of MMP degradation, through its sequence and/or concentration [6]. In this study, RAD16-II peptide nanoscaffold was used as a controlled system to test the hypothesis that fibroblasts regulate angiogenesis via modifying the extracellular mechanical environment through mechanisms including cell-mediated scaffold disruption and matrix remodeling.
Material Uncertainties and the Mechanistic Modeling of the Human Knee
Authors: Dhaher Yasin Y. , Barry Megan , Sun Qunli
Published: July 2013

Biomechanical models of articular joints are highly useful for understanding joint functions in normal and pathological states (c.f. [1]). The accuracy, however, of the model predictions is a complex function of the model structure/formulation (number of degrees-of-freedom) and uncertainties associated with the model constituents including properties of the joint’s soft tissues. Previous studies have provided extensive experimental quantification of knee joint soft tissue properties for use in developing and validating numerical models of these tissues [2]. However, there are as of yet no quantitative analytical studies on the impact of material property uncertainties on the prediction of joint kinematics or kinetics.
Fluid Shear Stress Reduces Simvastatin Induced Adhesion Molecule Expression in Cytokine Activated Endothelial Cells
Authors: Rossi Joanna , Rouleau Léonie , Tardif Jean-Claude , Leask Richard L.
Published: July 2013

Although originally designed as inhibitors of cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, are now known to also have non-lipid lowering benefits [1]. Statins have been reported to modulate gene expression in endothelial cells, however, the effect of statins on adhesion molecule expression is contradictory. Some studies report a decrease in adhesion molecule mRNA and/or protein after statin treatment [2], while others have shown that statins potentiate the effect of tumor necrosis factor alpha (TNFα) [3]. To the best of our knowledge, the effects of statins on gene expression in cultured endothelial cells has been done in static conditions only and no study has examined the effect of blood flow. This is particularly important since fluid shear stress is a strong regulator of endothelial cell function and phenotype [4]. The purpose of this study was to clarify the effects of statins on vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) expression in endothelial cells by evaluating their biological response under fluid flow.
Crouch Gait Represents a Simplified Muscular Support Strategy During Single-Limb Stance Compared to Unimpaired Gait
Authors: Steele Katherine M. , Seth Ajay , Hicks Jennifer L. , Schwartz Michael , Delp Scott L.
Published: July 2013

For patients with cerebral palsy who walk in a crouched posture, gait is often a strenuous activity. In order to improve gait, surgeons and therapists attempt to identify individual muscles that can be strengthened, surgically lengthened, or otherwise treated to improve patients’ abilities to support their body weight and propel themselves forward. However, little is known about the role of individual muscles during crouch gait, and current treatments often produce inconsistent results. The goal of this study was to identify which muscles are employed during crouch gait to support the body during single-limb stance. Understanding how the support strategy of crouch gait compares to unimpaired gait can provide insight into the underlying causes of crouch gait. Traditional movement analysis cannot fully characterize the role of individual muscles during gait. Therefore, we developed dynamic simulations to examine the contribution of lower-extremity muscles to support and progression.
The Effect of Surface Tension on the Epithelial Spreading of Non-Newtonian Drug Delivery Vehicles: Numerical Simulations
Authors: Hu Bin , Kieweg Sarah L.
Published: July 2013

This paper is one of the components of our research on how to optimize polymeric drug delivery vehicles. One of the applications is in the topical delivery of anti-human immunodeficiency virus (HIV) gels called microbicides [1]. Microbicides are delivered to vaginal or rectal epithelium to protect it from HIV and other sexually transmitted infections. Microbicides may provide a physical barrier amplifying the normal vaginal defense, as well as destroy the pathogens chemically or inhibit viral infection. The microbicide may consist of an anti-HIV active agent in some delivery vehicle, such as a gel, cream or foam. Microbicides are a promising solution to provide a low-cost, female-controlled method for protection against HIV and other sexually transmitted pathogens.
Real-Time Model-Based Gait Retraining for Knee Osteoarthritis Rehabilitation
Authors: Walter Jonathan P. , Pun Hugh , Chmielewski Terese L. , Chan Newton , Fregly Benjamin J.
Published: July 2013

According to the Arthritis Foundation, 66 million Americans (or nearly 1 in 3 adults) currently suffer from arthritis, with osteoarthritis (OA) being the most common form, and the knee being the joint most commonly affected. Despite the need for early treatment, few clinical interventions slow the progression of knee OA. Since articular cartilage is responsive to the amount of joint loading, reducing compressive loads in the diseased compartment may slow the rate of cartilage breakdown. Because medial compartment load cannot be measured non-invasively in vivo, an external measure to quantify the desired load reduction has been sought. The best candidate found thus far is the external knee adduction moment during gait [1]. This moment exhibits two peaks during the gait cycle, one during early stance phase and the other during late stance. A high peak knee adduction moment has been correlated with increased disease severity [2] and an increased rate of disease progression [3].
A Novel, Label-Free Method for Quantifying Collagen Fibril Formation and Degradation Using DIC Microscopy, Electromagnetic Wave Theory, and Image Processing
Authors: Flynn Brendan P. , Bhole Amit , DiMarzio Charles , Ruberti Jeffrey W.
Published: July 2013

Methods to assay fibrillar growth and degradation at sub-light scales include: fluorescence assays using FITC-collagen or FRAP, destructive preparation and measurement using electron microscopy, and light occlusion methods including turbidity and absorption methods. Many of these methods require the outright destruction, or at least modification via labelling, of the sample in question. This requirement can slow experimentation and introduce additional variability or even alter the reaction rate kinetics. The two methods (absorption and turbidity) which are label-free are bulk averaging methods and cannot isolate subsets of fibrils (e.g. fibrils under load).
Rheology of Cancer Cells With Different Metastatic Properties
Authors: Yoshimoto T. , Ishikawa T. , Matsuki N. , Fujiwara H. , Imai Y. , Ueno H. , Takeda M. , Yamaguchi T.
Published: July 2013

Cancer is the leading cause of death in Japan as well as many other countries. One of the most serious problem of cancer is that cancer cells often migrate to a distant part of the body, referred to as metastasis. The rheological properties of cancer cells have been investigated by some reserchers [1,2]. However, the correlations between the metastasis and the rheological properties are still unclear, because of limited number of experimental cases reported so far. In this study, we used two kinds of human breast cancer cell lines, MCF-7 and KPL-4. It is known that KPL-4 has much higher metastatic property than MCF-7. The rheological properties of these cells were measured by a micropipette aspiration method [3,4]. By comparing Young’s modulus between two kinds of cancer cells, we discuss the correlations between the metastasis and the cell deformability.
A Fast Simulator to Model Complex Tendon-Bone Interactions: Application to the Tendinous Networks Controlling the Fingers
Authors: Kurse Manish , Lipson Hod , Valero-Cuevas Francisco
Published: July 2013

Forces generated by the muscles actuating the fingers are transmitted through a complex network of tendons. Current models of the hand either ignore or simplify the structure of these networks [1]. It has been shown that the deformable nature of these tendinous networks results in a nonlinear transformation of muscle forces [2]. Our long-term objective is to understand how the topology of this network affects the control of finger force and motion. To achieve this, we will use a machine learning approach to evolve models of this network that can best replicate experimental results [3]. Here we present an anatomically realistic solver developed to model mechanical force transmission by a network of tendons in the human fingers. While most existing solvers neglect mechanics of tendon networks, there has been recent work on dynamic simulators accounting for tendon-bone interactions [4]. The solver we present here advances work in this field by being able to simulate mechanics of complex networks wrapped on arbitrarily shaped objects (like bones), and can be effectively used to model isometric force production in complex biomechanical systems. Its speed makes it an ideal simulation engine for the evolutionary algorithms we use to infer complex anatomical structures from sparse experimentation [3].
One-Step Reverse-Transcription PCR on a High-Throughput Micro-Fluidic Device
Authors: Fleming Paul , Dalton Tara
Published: July 2013

One step reverse-transcription polymerase chain reaction (RT-PCR) assays are an attractive option for further automating gene detection assays. One-step assays can reduce hands–on-time and the risk of sample crossover and contamination. The one-step chemistries are showing increasing use in virus detection and have been reported, in some cases, to be more appropriate than their two-step counterparts [1, 2].

Previous work presented by the Stokes Institute research group outlined a micro fluidic based continuous flow instrument which performed high throughput qPCR in nanolitre sized droplets [3]. This instrument had advantages over commercially available instruments in that it could process far more than the traditional 96 or 384 reaction setup in a single run and the reaction volume was reduced from 20–50 μl down to 30–100 nl sized droplets.

Combining one-step chemistry with the technology offered by the devices being developed would lead to a high-throughput RNA-to-signal system capable of reverse transcribing and performing PCR on thousands of nanolitre sized reactions every day. It is envisaged that this technology will also lead to gene expression from single cells contained in nanolitre sized droplets.

In this paper, a study was conducted in which an extra thermal region, manufactured from aluminium, was added to the existing continuous flow instruments. This region was maintained at a temperature suitable for reverse transcription, which was 48°C for the one-step kit tested. The thermal region was also a suitable length to maintain the sample at the required temperature for 15 minutes. Using a commercially available one step RT-PCR kit (TaqMan® RNA-to-CT™ 1-Step Kit, 4392653), the device was evaluated for its potential to perform one-step RT-PCR in continuously flowing nanolitre sized droplets.

Electrophoresis gels were initially used in assessing specific amplification before an end-point detection method was utilized. RNA was extracted from the leukemic REH cell line with the housekeeping gene, glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) as the gene of interest. To investigate the possibility of further reducing sample preparation and facilitating further automation, amplification from cell lysates without nucleic acid extraction was carried out on the device. Cell lysates were prepared using the cell lysis buffer from the TaqMan® Gene Expression Cells-to-CT™ Kit (Cat #AM1728). It was found that the device was successful in one-step RT-PCR from extracted RNA samples and samples from cell lysates without nucleic acid extraction.
Increased Light Transport in Skin Using Mechanical Compression
Authors: Drew Chris W. , Izquierdo-Roman Alondra , Liu Yajing , Rylander Christopher G.
Published: July 2013

The complex morphological structure of skin with its variations in the indices of refraction of components therein provides a highly scattering medium for visible and near-infrared wavelengths of light. “Tissue optical clearing” increases transmission of near-collimated light in biological tissue, potentially enabling improved optical analysis and treatment techniques. Numerous methods of tissue optical clearing have been hypothesized using hyperosmostic agents [1]. These methods propose reduction in light scattering by means of dehydration of tissue constituents, replacement of interstitial or intracellular water with higher refractive agents, or structural modification or dissociation of collagen fibers [2]. It has been suggested that dehydration of tissue constituents alone can reduce light scattering by expulsing water between collagen fibrils, increasing protein and sugar concentrations, and decreasing refractive index mismatch [3].
Computational Analysis of Cementation Techniques for Total Knee Arthroplasty
Authors: Kelly Nicola , Cawley Derek , Shannon Fintan J. , McGarry Patrick J.
Published: July 2013

Tibial implant component loosening is the most common cause of aseptic total knee arthroplasty (TKA) failure. Stability of a primary TKA relies on adequate fixation and therefore the cementation technique used may provide an enhanced clinical result. Surface cementation and full cementation techniques are employed to achieve fixation in TKA. Full cementation entails the application of bone cement on the tibial cut surface and along the keel; while surface cementation is the application of cement solely on the proximal tibial cut surface.
Load Sharing Among Plantar Structures in the Foot: A Computational Analysis of Arch Stability
Authors: Iaquinto Joseph M. , Wayne Jennifer S.
Published: July 2013

The passive support structure of the medial arch of the foot is a complex three dimensional amalgamation of small but highly detailed bones surrounded by a complex tight weave of ligamentous connective tissue. This structure preserves the shape of the foot and dissipates loads in day to day walking over a lifetime. Though the entirety of the structure is functionally important, there are several components under scrutiny due to their location, size, and prominent role in arch strength.
Estimation of the Arterial Mechanical Properties Based on a Patient Specific Wave Propagation Model Using a Stochastic Method
Authors: Leguy Carole A. D. , Bosboom E. Marielle H. , Gelderblom Hanneke , van de Vosse Frans N.
Published: July 2013

Arterial stiffness is an independent predictor of cardiovascular risk [1]. It is therefore crucial to accurately estimate the arterial mechanical properties. The mechanical properties are reflected in the pulse wave velocity (PWV), which can be estimated from the blood pressure (BP) waveforms measured at two locations (tonometry). However, accuracy of tonometry is limited by reflections in the BP waveforms and errors in distance estimation between the measurement sites.
Deformations During and Post Stenting of a Diseased Coronary Artery Phantom: An In Vitro Study
Authors: Finn Ronan , McGloughlin Tim , Delassus Patrick , Morris Liam
Published: July 2013

World-wide, deaths from cardiovascular diseases exceed those caused by cancer, infectious disease and trauma [1]. Coronary stenting is an established treatment for patients with symptomatic coronary artery disease. Although stents reduce restenosis rates in carefully selected lesions, in-stent restenosis remains a recognized clinical problem. Restenosis, defined as “the arterial healing response after injury during transluminal coronary revascularisation” [2], has been the principal drawback of coronary stenting since its conception nearly 30 years ago [3]. While there have been many studies on the short and long term effects of coronary artery stenting, less is known of the injury caused by the balloon and stent during the stenting process. The objective of this study is to fabricate compliant and morphologically realistic models of the right coronary artery (RCA) for preclinical bench-top testing of intraluminal stents, in diseased cases.
Microstructural Alterations in the Human Sclera: Do Age and Race Matter?
Authors: Yan Dongmei , Vande Geest Jonathan P.
Published: July 2013

Glaucoma, an ocular disease resulting from a loss of retinal ganglion cell function, is the second leading cause of blindness in the world, according to the World Health Organization. Approximately 120,000 are blind from glaucoma, accounting for 9% to 12% of all cases of blindness in the U.S. Earlier studies have suggested that mechanical forces play a critical role in the progression of glaucoma [1–3]. Sigal, Flanagan, et al. studied the influence of varied factors including geometric features and material properties using both generic and individual-specified optic nerve head (ONH) models developed in their work, and they demonstrated that scleral mechanical properties had by far the largest influence in the ONH biomechanical environment (ONH strain) [4–8]. Downs, Burgoyne, et al. defined the effects of the scleral shell and collagen fiber orientation through the examination of displacement [9]. The above studies show that the ONH mechanical properties depend strongly on the microstructure in the scleral shell.
Design of Optically Accessible, Ultra Low-Volume, Tissue Loading Bioreactor
Authors: Patenaude Jeffrey A. , Desjarlais Aaron , Kornfeld Jessica , Lee Michael , McGrath Matthew , Perry Jeffrey , Ruberti Jeffrey W.
Published: July 2013

Given mounting evidence that mechanical force is a critical parameter in the normal development and remodeling of load-bearing tissue, there is a critical need for a new class of bioreactors which can apply controlled loads/strains to tissues or engineered constructs while permitting high-powered optical accessibility. We have developed a novel bioreactor which can be mounted onto the stage of an inverted microscope which permits direct 600× observation of a perfused specimen while the specimen is held in either load or strain control. Further, the chamber has been designed to minimize free volume to reduce the cost of reagents.
Age and Location Dependent Microstructural and Biomechanical Characterization of Human Aortas
Authors: Haskett Darren , Johnson Greg , Vande Geest Jonathan
Published: July 2013

The stiffening of the aorta with age is well documented in humans [1]. Collagen, elastin and smooth muscle cells are primarily responsible for the load bearing functionality of the human aorta, and it is generally accepted that imbalances in the organization of these components occur with age and in the presence of disease [2]. While a detailed account of the structural organization of the human aorta has been reported by a few investigators, none of these quantify simultaneously the organization of both collagen and elastin and how these change with age and location along the aortic tree. Additionally, none of these studies accurately assess how these changes result in corresponding alterations in the biomechanical function of the aorta.
In-Vivo Lumbar Intervertebral Disc Geometric Deformation During Functional Postures
Authors: Wang Shaobai , Passias Peter G. , Xia Qun , Wood Kirkham B. , Li Guoan
Published: July 2013

Degeneration of the intervertebral disc is responsible for the vast majority of back pain. Significant efforts have been made to characterize lumbar intervertebral disc (IVD) deformation during physiologic functional postures in an attempt at understanding the mechanisms resulting in disc related spinal disorders and improving their surgical treatment. However, the details of IVD deformation, including the magnitude and direction of tension and shear, have yet to be clearly defined in-vivo mainly due to technical limitations. This study investigated lumbar IVD geometric deformation from translation and orientation of the adjacent level endplates using a combined MR and fluoroscopic image matching technique [1]. Tensile and shear deformation was quantified by comparing IVD deformation at flexion and extension positions to standing position at the L2-L5 vertebral levels.
Comparison of Regional Lung Deformation Between Dynamic and Static CT Imagery Using Inverse Consistent Registration
Authors: Amelon Ryan , Ding Kai , Cao Kunlin , Christensen Gary E. , Reinhardt Joseph M. , Raghavan Madhavan
Published: July 2013

The mechanics of lung deformation is traditionally assessed at a whole-lung or lobar level. We submit that key aspects of lung mechanics maybe better understood by studying regional patterns of lung deformation by leveraging recent developments in tomographic imaging and image processing techniques. Our group has developed an inverse consistent registration technique for estimating local displacement distributions from paired lung CT volumes [1,2]. This facilitates the estimation of strain distributions and consequently, the regional patterns in volume change and its preferential directionalities (anisotropy in deformation). In this study, we use this novel method to compare regional deformation in the lungs between static and dynamic inflations in an adult sheep. Much of our research has focused on registration of static lung images at different positive end-expiratory pressures (PEEP). More recently, respiratory-gated CT scans of supine, positive-pressure inflated sheep lungs have been gathered in order to compare the displacement fields of a dynamically inflating lung to the static lung scans. The theory is that scanning a dynamically inflating lung will more accurately reflect natural deformation during breathing by realizing time-dependent mechanical properties (viscoelasticity). The downside to human dynamic lung imaging is the increased radiation dose necessary to acquire the image data across the respiratory cycle, though low-dose CT scans are an option [3]. This experiment observed the difference in strain distribution between dynamically inflated lungs versus static apneic lungs using the inverse consistent image registration developed in our lab.
Mechanical Properties of Collagen-Fibrin Co-Gels
Authors: Lai Victor K. , Sander Edward A. , Tranquillo Robert T. , Barocas Victor H.
Published: July 2013

Achieving desired mechanical properties is critical to meeting the functional requirements of engineered tissues. Mechanical function is inextricably linked to tissue structure. For example, replacement of fibrin with collagen during the healing process results in compositional heterogeneity which governs mechanical strength and function. Artificial tissues engineered using biopolymers such as fibrin and collagen can undergo a remodeling process that produces a compositionally and structurally complex tissue equivalent (TE) with anisotropic mechanical properties. TE functionality is assessed in part through mechanical testing, but the TE response is dependent on multi-scale interactions, which are dependent on a heterogeneously distributed microstructure, and are therefore difficult to interpret. In order to unravel the coupling between TE microstructure and macroscopic mechanical behavior, we have developed a multi-scale modeling framework for incorporating single component microstructural networks [1]. To expand our modeling framework, it is necessary to incorporate interpenetrating fibrin and collagen networks. This issue is particularly critical towards understanding the remodeling process that occurs in fibrin gels, which gradually replace fibrin with collagen networks. In this work, we have begun to investigate interpenetrating fibrin-collagen co-gels by varying the co-gel composition and subjecting the gels to uniaxial mechanical tests [2]. This study lays the experimental foundation for determining how to construct interpenetrating networks for our multiscale modeling framework, which will ultimately allows us to better assess and predict TE mechanics and produce better engineered tissues.