bluuebunny/crossref_metadata_2025 huggingface dataset:
A Microstructural Data Driven Multiscale Model for the Enzymatic Degradation and Remodeling of Collagen Networks
Authors: Hadi Mohammad F. , Sander Edward A. , Ruberti Jeffrey W. , Barocas Victor H.
Published: July 2013

Collagen proteases actively participate in remodeling soft tissues. Recent work has demonstrated that metalloproteinases (MMP) and bacterial collagenases (BC) exhibit strain-dependent degradation kinetics [2]. Ascertaining how such nanoscale degradation shapes collagenous tissues at the macroscale is vital to our understanding of collagen management within tissues. As a first step towards this goal, we have developed a multiscale model for the enzymatic degradation and remodeling of collagen networks. Such a model will be useful in understanding the etiology of diseases related to collagen management (such as arthritis and fibrotic disorders), in simulating soft tissue development, and in helping engineer improved biomimetic tissues.
Tailoring the Gross Morphology of the Tendon-to-Bone Insertion for the Reduction of Stress Concentrations
Authors: Liu Yanxin , Birman Victor , Chen Chanqing , Thomopoulos Stavros , Genin Guy M.
Published: July 2013

Attaching dissimilar materials is a major challenge in engineering, and has proven to be a challenge in surgical practice as well [1]. At the tensile connection of tendon to bone, a two order-of-magnitude mismatch exists, leading to stress concentrations and the potential for failure [2–3]. Here, we examine one material attachment strategy employed at this connection to achieve effective load transfer between a healing tendon and bone: shaping of gross tissue morphology [4]. Our ultimate goal is to understand the mechanisms of stress transfer at the tendon-to-bone insertion. This understanding may lead to biomimetic attachment strategies that will benefit engineering practice and improve surgical healing outcomes.
Full Cardiac Cycle Strain Measurement Using Hyperelastic Warping, Application to Detecting Myocardial Dysfunction in Rat microPET Images
Authors: Farrar G. E. , Gullberg G. T. , Veress A. I.
Published: July 2013

Assessments of regional heart wall deformation (wall motion, thickening, strain) are commonly used to evaluate left ventricular wall function in the clinical setting. Nuclear based imaging modalities such as PET and SPECT are commonly used to localize ischemic myocardial disease, and can identify impairment of cardiac function due to hypertrophic or dilated cardiomyopathies. Regional wall motion analysis in conjunction with global left ventricular (LV) ejection fraction is commonly used to assess systolic and diastolic function. The quantification of ventricular strains throughout the entire cardiac cycle provides valuable information that could be used to more effectively differentiate between diastolic and systolic dysfunction, as well as a more complete picture of overall cardiac performance.
Three Dimensional Cellular Loading and Average Microstructural Tissue Response Using Single and Three Cell Models
Authors: Halloran Jason , Sibole Scott , Erdemir Ahmet
Published: July 2013

Finite element analysis of single cells embedded in an extracellular matrix have been used widely to provide new insights into the cellular loading in cartilage [1] and meniscus [2]. Deformations derived from a homogeneous tissue model are generally used to drive simulations using microstructural representations. Implicit in this setup is the assumption of the equivalence of macrostructural (tissue) constitutive response and average stress-strain response of the microstructural (cellular) model. Higher cell densities within tissue volume [3] may increase the uncertainty introduced by this assumption and may also influence how macroscopic loads are transferred to the cells. We have previously shown, albeit with a two-dimensional simulation, the potential mismatches in such variables for increasing strain level and cell density, specifically for no cell, one, and three cell representations [4]. Hence, the objective of this study was to quantify the differences between the overall response and cellular deformation in three-dimensional nonlinearly elastic microstructural cartilage models embedded with either one or three cells. Multiscale coupling approaches targeting prediction of cell deformations from tissue and/or organ level loading will likely benefit from this investigation while balancing computational demand with accuracy requirements.
Non-Thermal Dielectric Barrier Discharge Plasma Promotes Vascularization Through Reactive Oxygen Species
Authors: Arjunan Krishna Priya , Friedman Gary , Clyne Alisa Morss
Published: July 2013

Angiogenesis, the growth of new blood vessels from existing vessels, plays a key role in growth, and wound healing. Insufficient vascularization contributes to impaired wound healing in diabetic patients and the elderly. Tissue engineering is limited by the inability to adequately vascularize constructs to provide nutrients to the tissue core, thus limiting the size of engineered organs.
Influence of Intermittent Pneumatic Compression on Wall Shear Stress and Nitric Oxide Levels
Authors: Swaminathan Ganesh , Thyagaraj Suraj , Loth Francis , McCormick Susan , Bassiouny Hisham
Published: July 2013

Wall shear stress (WSS) in blood vessels has been shown to play an important role in the development of atherosclerosis. In particular, regions of low and oscillating WSS have been shown to correlate with the localization of atherosclerosis. Thus, we hypothesize that increasing the WSS for patients with peripheral vascular diseases (PVD) will either reduce PVD severity or slow its progression. We analyzed WSS changes from a study by Delis et al. on 32 limbs of PVD patients [1]. Results show that intermittent pneumatic compression (IPC) increases mean WSS by 170% and 240% in PVD patients and healthy subjects, respectively. Peak WSS was found to increase by 93% and 40% in PVD patients and healthy subjects, respectively. In addition, we examined changes in NOX level with use of IPC on five limbs from PVD patients. Our study demonstrated increased NOx levels in subjects after IPC. Further research is needed to determine the benefits of IPC for PVD patients.
Effects of Passaging on the Migration Response of Synovium-Derived Stem Cells to an Applied DC Electric Field
Authors: Tan Andrea R. , Alegre-Aguarón Elena , Dujari Divya N. , Sampat Sonal R. , Bulinski J. Chloë , Ateshian Gerard A. , Hung Clark T.
Published: July 2013

Strategies for cartilage tissue engineering and repair have recently focused on cell sources from the surrounding joint tissue as an alternative to chondrocytes. Synovium-derived stem cells (SDSCs) are found in the intimal layer of the synovium, the thin overlying capsule surrounding the joint space [1] and have been found to exhibit a greater chondrogenic potential than stem cells from other origins such as bone marrow stem cells or adipose derived stem cells [2–4]. Under directed cues, these cells have been shown to be capable of migrating from the synovium membrane into articular cartilage defects, though the mechanism behind such movement is unclear. As a first step, we have previously shown that SDSCs expanded in 2D monolayer culture in a growth factor cocktail of TGF-β1, FGF, and PDGF-ββ exhibit directed cathodal migration with perpendicular alignment when under the influence of an applied DC electric field [5]. As cellular behavior and response to an external stimulus can change with exposure to growth factors and passage number, we look here to characterize the effects of passaging on the migration response of SDSCs to an applied electric field. We hypothesize that if these cells develop more chondrocyte-like characteristics with growth factor passaging, their response will mimic that which has previously been reported for chondrocytes, notably directed cathodal (negative pole) migration and perpendicular realignment of the long axis to the direction of applied field [6].
Evaluating the Risk of Eye Injuries: Intraocular Pressure During High Speed Projectile Impacts
Authors: Alphonse Vanessa D. , Bisplinghoff Jill A. , Senge Danielle M. , McNally Craig , Duma Stefan M.
Published: July 2013

In order to predict and possibly prevent ocular injuries for various impact scenarios, previous research investigated injuries from projectile impacts with known characteristics. Normalized energy was determined as the most significant predictor of injury type and tissue lesion. Although studies have reported the injury risk for projectile impacts to the globe, none have reported the corresponding intraocular pressure [1]. Quantifying intraocular pressure during impacts may provide insight to vision problems such as glaucoma and cataracts. Therefore, the purpose of the current study is to determine intraocular pressure during high speed projectile impacts to eyes.
Collagen Fiber Angle Quantification of Carotid Arteries From Fibulin-5 Null Mice
Authors: Wan William , Gleason Rudolph L.
Published: July 2013

Recent studies have revealed that carotid arteries from fibulin-5 (fbln5) null mice exhibit altered biomechanical and microstructural properties [1–2]. While the previous studies outline quantitative differences in mechanical properties of arteries from fbln5 null and wildtype mice, physical microstructural differences have yet to be quantified. Measurement of microstructural parameters will provide a crucial link between previously quantified mechanical properties and biological effects of knocking out the fbln5 gene. Characterizing microstructural properties will also provide experimental data to validate structurally-motivated constitutive relations and growth and remodeling models [3–4]. In this study, we quantified collagen fiber orientation in carotid arteries from fbln5 null and wildtype mice; collagen in mouse carotid arteries were imaged using multiphoton microscopy and analyzed using a fast Fourier transform algorithm.
Fabrication, Characterization, and Bioactivity of Multi-Compartment Collagen-GAG Scaffolds for Orthopedic Interfaces
Authors: Weisgerber Daniel , Caliari Steven , Gonnerman Emily , Yapp Rebecca , Insana Michael , Harley Brendan
Published: July 2013

It has been estimated that over 62 million tendon and ligament injuries occur every year. The failure rate for these injuries can be despairingly high, such as 94% in the case of rotator cuff injuries. One possible cause for these failures is the inadequate recapitulation of the interface between the two mechanically and chemically different tissues, like bone and ligament or bone and tendon. In particular, we are developing a multi-compartment regenerative scaffold designed to mimic the distinct tendinous and osseous compartments as well as the continuous interface. Such a scaffold could induce the physiological wound healing processes in critical defects, while maintaining the mechanical and chemical properties inherent in the native tissue. The present project is developing the necessary fabrication, characterization, and bioactivity analysis strategies for a multi-compartment collagen-glycosaminoglycan (CG) and calcium phosphate mineralized CG (CGCaP) scaffold with a gradient in mineral content, specifically mimicking the bone-tendon-junction (BTJ) site.
Effects of Surgical Repair or Reconstruction on Radiocarpal Mechanics From Wrists With Scapholunate Injury
Authors: Johnson Joshua E. , Lee Sang-Pil , McIff Terence E. , Toby E. Bruce , Fischer Kenneth J.
Published: July 2013

Scapholunate dissociation (SL ligament disruption) due to trauma can cause changes in joint kinematics and contact patterns, which can lead to scapholunate advanced collapse (SLAC wrist) with secondary radiocarpal osteoarthritis (OA) [1]. The relationship between consequent abnormal mechanics and the onset of OA is not clearly understood, however elevated joint contact pressure is believed to be an associated factor. Knowing how injuries affect joint physiology and mechanics and how well surgical repairs restore the mechanics may improve surgical efficacy and help predict OA risk. Recently a method was proposed to measure joint contact mechanics from in vivo imaging data during functional loading [2]. The objective of this study was to compare radiocarpal joint mechanics (contact forces, contact areas, peak and average contact pressures) of injured and post-operative wrists to contralateral controls using MRI-based contact modeling. We hypothesized that average contact pressures and peak contact pressures would be higher in the injured wrists, and that these measures would decrease post-operatively.
Cervical Spine Movement Sequencing During Flexion-Extension
Authors: Anderst William J. , Schafman Michelle , Donaldson William F. , Lee Joon Y. , Kang James D.
Published: July 2013

Static flexion-extension x-rays are the most common clinical tool used to assess abnormal motion of the cervical spine. Despite their widespread use (over 168,000 cases per year), the clinical efficacy of flexion-extension radiographs of the cervical spine has yet to be proven1. Limitations of static flexion-extension x-rays include data collection during static positions that may not accurately represent dynamic behavior, and the fact that data is collected at end range of motion positions, not in more frequently encountered mid-range positions. Consequently, static x-rays may not reveal movement abnormalities that occur during activities of daily living and lead to pain and degeneration. Therefore, it may be advantageous to analyze cervical spine kinematic data collected during dynamic, functional movements performed through an entire range of motion (not just the endpoints). Furthermore, the literature confirms there is substantial variability in “normal” range of motion and translation during flexion-extension1, making it difficult to reliably identify abnormal motion. Therefore, it may also be beneficial to evaluate alternative motion parameters that may reliably identify abnormal motion.
Dynamic Trunk Control Influence on Run-to-Cut Maneuver: A Risk Factor for ACL Rupture
Authors: Jamison Steve T. , Pan Xueliang , Chaudhari Ajit M. W.
Published: July 2013

Anterior Cruciate Ligament (ACL) rupture is one of the most common serious knee injuries in field and court sports, with an estimated 70% of these injuries being non-contact in nature, often from sudden changes in direction or pivoting [3]. ACL injury results in both short- and long-term consequences for the athlete, which may include surgery, decreased activity levels, elevated pain levels during activities and increased risk of osteoarthritis. Previous studies have shown that knee abduction and tibial internal rotation moments independently strain the ACL, and that these moments have an interaction effect at physiologic load levels, creating strains approaching the reported range of ACL rupture [2, 6–8].
Cervical Spine Bone Mineral Density as a Function of Vertebral Level and Anatomic Location
Authors: Thorhauer Eric , Anderst William , Donaldson William , Lee Joon , Kang James
Published: July 2013

Quantitative computed tomography (QCT) scans have been used to estimate bone mineral density (BMD) measurements, which in turn have been shown to correlate with bone mechanical properties such as strength, stiffness and yield load1,2. Information on the variation of BMD in the cervical spine with respect to anatomic location and vertebral level does not currently exist. This would be beneficial to vertebral instrumentation designers and to basic scientists who assign mechanical properties of bones in finite element models of the spine. Previously, bone mineral density measurements of the cervical spine have been performed almost exclusively on the central vertebral body, either by measuring trabecular BMD in a single CT slice 1, 3, 4 or by measuring a large volume of trabecular bone in multiple CT scan slices 5,6. In addition to the central vertebral body, the only other BMD measurements of specific anatomical regions were performed on the endplates 2, 3.
Assessing the Effect of Matrix Metalloproteinase-9 on the Growth of Mice Teeth
Authors: Ni Qingwen , Chen Shuo
Published: July 2013

Dentin and bone are formed when odontoblasts and osteoblasts synthesize and secrete collagen type I-rich extracellular matrix that mineralizes in a highly controlled manner. A wide spectrum of mouse and human disorders affecting tooth and bone biomineralization shows that dentin and bone formation are under strict genetic control. Although the controlling mechanisms of dentinogenesis and osteogenesis require further study, a large body of evidence points to the importance of the matrix metalloproteinases (MMPs) participate in a wide variety of extracellular matrix degradation. Detailed knowledge of MMPs may be important for understanding the pathogenesis of tooth development. Some researchers have pointed MMP-9 is an extracelluar proteinase that is highly expressed in osteoclasts and has been postulated to play an important role in their resorptive activity. Although MMP-9 has been reported to play a role in bone resorption, the association of this enzyme during deciduous tooth resorption has not yet been clarified. Based on accumulating evidence, we hypothesized that MMP-9 should play a role in teeth attrition. In this study, we have applied NMR relaxation technique to assess age-related MMP-9 KO tooth quality in vitro by quantifying changes in dentin and pulp simultaneously. The major hypothesis in this paper was that whether noninvasive NMR relaxation time measurements could be used to characterize MMP-9 KO changes in dentin and pulp, and to predict tooth quality. Specifically, we tested that age-related MMP-9 KO tooth changes result in an alteration of the NMR spin-spin (T2) relaxation time signal due to the structural changes in the tooth matrix. This signal can be further processed to produce a T2 relaxation distribution spectrum related to dentin and pulp, and their derived parameters can be used as descriptors of age-related MMP-9 KO tooth changes. In this study, the proton liquid-like NMR spin-spin (T2) relaxation decay signal was obtained from the Carr-Purcell-Meiboom-Gill (CPMG) NMR spin echo train method [1,2], then the relaxation decay signal was converted to T2 relaxation distribution spectra describing the size domain of dentin and pulp. Therefore, we can calibrate the intensities in NMR inversion T2 relaxation distribution spectra corresponding to the amount of dentin and pulp related to the structural changes. Here, we propose an NMR calibration method “NMR standard estimation” — the ratio of the amount of pulp to the amount of dentin obtained from NMR T2 distribution spectra that can be used to measure the age-related MMP-9 KO structural changes in teeth [3]. We are cognizant of the biological and physiological variability manifest in teeth size variations, but feel that this kind of NMR standard estimation — the ratio of amount of dentin to amount of pulp from the NMR T2 inversion spectrum can be used to determine age-related MMP-9 KO structural changes in teeth and eliminate any variations in size of teeth.
Engineering Tools for Studying Coordination Between Biochemical and Biomechanical Activities in Cell Migration
Authors: Na Sungsoo
Published: July 2013

Cell migration is achieved by the dynamic feedback interactions between traction forces generated by the cell and exerted onto the underlying extracellular matrix (ECM), and intracellular mechano-chemical signaling pathways, e.g., Rho GTPase (RhoA, Rac1, and Cdc42) activities [1,2,3]. These components are differentially distributed within a cell, and thus the coordination between tractions and mechanotransduction (i.e, RhoA and Rac1 activities) must be implemented at a precise spatial and temporal order to achieve optimized, directed cell migration [4,5]. Recent studies have shown that focal adhesions at the leading edge exert strong tractions [6], and these traction sites are co-localized with focal adhesion sites [7]. Further, by using the fluorescence resonance energy transfer (FRET) technology coupled with genetically encoded biosensors, researchers reported that Rho GTPases, such as RhoA [8], Rac1 [9], and Cdc42 [10] are maximally activated at the leading edge, suggesting the leading edge of the cell as its common functional site for Rho GTPase activities. All these works, however, were done separately, and the relationship between tractions and mechanotransduction during cell migration has not been demonstrated directly because of the difficulty in simultaneously recording tractions and mechanotransduction in migrating cells, precluding direct comparison between these results. Furthermore, these studies have been conducted by monitoring cells on glass coverslips, the stiffness of which is ∼ 65 giga pascal (GPa), at least three to six order higher than the physiological range of ECM stiffness. Although it is increasingly accepted that ECM stiffness influences cell migration, it is not known exactly how physiologically relevant ECM stiffness (order of kPa range) affects the dynamics of RhoA and Rac1 activities. For a complete understanding of the mechanism of mechano-chemical signaling in the context of cell migration, the dynamics and interplay between biomechanical (e.g., tractions) and biochemical (e.g., Rho GTPase) activities should be visualized within the physiologically relevant range of ECM stiffness.
Wide Range Logarithmic Gradient Formation for Cell Response
Authors: Hamon Morgan , Cramer Kirn , Jambovane Sachin , Dai Jing , Khademhosseini Ali , Hong Jong Wook
Published: July 2013

Recently, the number of potential drug targets has dramatically increased because of the recent completion of the human genome sequencing and the progress in genomics and proteomics. In parallel, the number of new drugs for those targets has also been increased due to the use of combinatorial synthesis and the increased access to natural molecules [1]. However, this has not increased consequently the number of approved new drugs delivered to patients [2]. Indeed the drug discovery process is still limited by numbers of challenges; among them the need to analyze in more rapid and accurate manner precious sample of drug candidates.
Ultrasonic Speckle Tracking for Measurement of Scleral Cross-Sectional Strains due to Intraocular Pressure Elevation
Authors: Tang J. , Liu J.
Published: July 2013

Glaucomatous vision loss can occur at both normal and elevated levels of intraocular pressure (IOP) and the optic nerve head (ONH) is the principle site of damage. The mechanical environment of the ONH is believed to be critical for retinal ganglion cell pathophysiology [1]. Previous computational models have shown that scleral mechanical properties play an important role in affecting the mechanical environment of the ONH [2]. It is thus important to characterize the mechanical behavior of sclera under physiological loadings. Ultrasonic strain mapping has been developed to measure the internal displacement and strain of soft tissue under external loadings [3, 4]. The purpose of this study was to examine the cross-sectional strain maps at the posterior sclera under IOP elevations using non-invasive ultrasound and a speckle tracking algorithm.
Hydration and Crosslinking Effects on the Elastic and Viscoelastic Properties of Collagen Scaffolds
Authors: Xu Bin , Zhang Katherine Yanhang
Published: July 2013

Collagen is the most abundant protein in the body. It plays critical roles in many supporting and connecting tissues such as tendon, ligament, bone, blood vessels, skin, etc. Collagen gels prepared from commercially available collagen solutions mimic the in vivo environment and have been widely used as three-dimensional (3-D) tissue scaffolds for cell culture. Collagen thin film is the dehydrated form of collagen gel. A number of studies have examined the cell-collagen thin film interactions (1, 2). As a biphasic material, collagen scaffolds contain a solid phase which represents by collagen fiber network and an interstitial fluid phase (3). This special structure makes collagen a viscoelastic material. Viscoelasticity is related to force or energy storage, transmission and dissipation in tissues and has a great influence on the growth and development of cells (4).
Uncertainty Analysis of the Mechanical Response of Porcine Brain at High Strain Rate Compression
Authors: Prabhu Rajkumar , Steele W. Glenn , Horstemeyer M. F. , Ryland Stephanie , Colebeck Erin E. , Whittington W. R. , Williams Lakiesha N. , Liao Jun
Published: July 2013

The Split-Hopkinson Pressure Bar (SHPB) apparatus presents a unique capability in studying the dynamic response of a material, but it is accompanied with a moderately high noise level, giving a rather large standard deviation for the stress-strain behavior of the soft biological material being tested [1]. Compounding the errors in a SHPB setup is the uncertainty arising from sample-to-sample variability in a soft biological material. Uncertainties arise in a measured variable through a vast number of sources such as an imperfect instrument calibration process, standards used for calibration, and the influence of the measured variable due to inconsistencies in ambient temperature, pressure, humidity and vibrations.
A Pipeline for High Throughput Post-Processing of Joint and Tissue Simulations for Estimation of Cell Level Deformations
Authors: Sibole Scott , Erdemir Ahmet
Published: July 2013

In biomechanics, the search for a better understanding of multiscale spatial interactions has become an increasingly desirable objective, in order to establish the causal mechanical relationships between the loading of joints, tissues, and cells. Experimental acquisition of mechanical data, while attainable [1], becomes more difficult to obtain as the spatial scale decreases. If one attempts to gather data at different spatial scales simultaneously, also under lifelike loading scenarios, the present technology is limited. Computational modeling, particularly when conducted in a multiscale fashion, may provide solutions and has often been employed to span spatial scales.
Three Dimensional Reconstruction of the Components of the Carotid Plaque From Standard CT Medical Images
Authors: Biswas Dipankar , Loth Francis , McCormick Susan , Bassiouny Hisham
Published: July 2013

The present study compares plaque and calcium volumes between sixteen diseased human carotid arteries. Half were from symptomatic patients, and half were from asymptomatic patients. In-house software was developed for the 3-D reconstruction of the plaque components from computerized tomography (CT) images. Results revealed higher mean total volume (TV) in the symptomatic group compared to the asymptomatic group. In contrast, the mean ratio of calcium volume (CV) to TV was lower for the symptomatic group compared to the asymptomatic group. This shows that symptomatic patients have a significantly greater plaque burden with minimal plaque calcification. The process of acquiring the data helped understand what tools/features are needed to conduct this work. One important feature of this software is the ability to create automated regions of interest (ROI) in addition to simple manual selection/modification of the ROIs in a GUI environment.
A Feature-Based Morphing Methodology for Biological Structures Applied to the Spatial Organization of Cardiomyocytes in the Left Atrium
Authors: Satriano Alessandro , Vigmond Edward J. , Di Martino Elena S.
Published: July 2013

When complex biological structures are modeled, one of the most critical issues is the assignment of geometrical, mechanical and electrical properties to the meshed surfaces. Properties of interest are commonly obtained from diagnostic imaging, experimental tests or anatomical observation. These parameters are usually lumped into individual values assigned to a specific region after subdividing the structure in sub-regions. This practice simplifies the problem avoiding the cumbersome assignment of parameter values to each element. However, sub-regions may not adequately represent the smooth transition between regions thus resulting in artificial discontinuities. In addition, some parameters, such as for example the organization of cardiomyocytes, which is the objective of our research, may be obtained through destructive tests or through sophisticated methods that can only be performed on a limited number of samples. Or else, data structure obtained for one animal species could be applied on a different species. Furthermore, in a clinical environment the need for fast turnout of patient-specific models would benefit from the assignment of tissue properties in a semi-automatic manner.
MPC-Collagen Gel Biologic Augmentations do not Promote Patellar Tendon Integration Into Bone
Authors: Kinneberg Kirsten R. C. , Galloway Marc T. , Butler David L. , Shearn Jason T.
Published: July 2013

The high failure rate of rotator cuff repair is often attributed to the fact that a normal zonal insertion site is not regenerated between tendon and bone. [1,2] Interestingly, a previous study in our laboratory demonstrated that a patellar tendon autograft (PTA) used to repair a central-third patellar tendon (PT) defect also does not regenerate a normal zonal insertion site at 12 weeks following surgery. Therefore, using our model of tendon healing, our objective was to design a biologic augmentation (BA) that could be implemented at the insertion site between tendon and bone to help promote integration. The results of this study have potential application in developing new techniques for rotator cuff repair.
Effect of Continuous-Flow Left Ventricular Assist Device on Cardiac Function: Simulation Study With a Biventricular Computer Model
Authors: Wang Yajuan , Ferreira Antonio , Keller Bradley B. , Simon Marc , Antaki James F.
Published: July 2013

Left ventricular assist device (LVAD) therapy has become an established treatment for patients with end-stage heart failure as either a bridge to transplant (BTT) or as permanent support (destination therapy: DT) [1]. For a small portion of patients, LVAD could be used as a bridge to cardiac recovery (BTR). Recent clinical studies have demonstrated the advantages of continuous-flow LVADs over pulsatile-flow counterparts with respect to higher survival rates and lower incidence of major adverse events [2]. However, the control challenge of continuous-flow LVADs has been not fully addressed: most of the devices are driven at a constant speed, which does not take into account changes in patient physiologic demands [3, 4].
Thin Film Flow of Polymeric Anti-HIV Microbicides: Comparison of 3-D Numerical and Experimental Simulations
Authors: Kheyfets Vitaly O. , Kieweg Sarah L.
Published: July 2013

In 2008, approximately 33.4 million people were living with HIV worldwide[1]. The rate of infection increases by about 5 million people per year[2], with a significant portion resulting from unprotected sex. A microbicide is a topical formulation that consists of a pharmaceutical agent suspended in a delivery vehicle (e.g. a polymeric liquid also called a “microbicide gel”), and could be a potential tool for preventing HIV transmission during intercourse. The vehicle itself can act as a physical barrier and, if designed with ideal physicochemical properties, might eliminate the need for a pharmaceutical agent altogether. In fact, a vehicle’s ability to coat the epithelium has been singled out as a crucial variable, which might dictate the microbicide’s efficacy[3]. Our overall objective is to develop an effective delivery vehicle that is capable of coating the vaginal epithelium under the influence of gravity, shearing, and compressive forces. The objective of this study is to numerically simulate the evolution of the 3-D free surface of a non-Newtonian fluid spreading under the influence of gravity. In addition, we aim to compare the spreading characteristics of the numerical model with experimental data, while incorporating similar initial conditions. Here, we present the advantages of accounting for lateral spreading in the numerical simulation.
Anabolic Effects of Ultrasound as Countermeasures of Simulated Microgravity in In-Vitro and In-Vivo Functional Disuse Models
Authors: Uddin Sardar M. Zia , Qin Yi-Xian
Published: July 2013

Microgravity (MG) during space flight has been known to cause adverse effect on bone quality. Data collected from studies done on spaceflights show loss of 1–1.6% bone mineral density (BMD) per space-flight-month[1]. Most BMD has been recorded in load-bearing bones [2]. Some studies has considered using drugs and different growth factors to maintain bone mass in microgravity conditions but it can be too expensive to maintain over longer periods of time besides the systematic effects of such treatments [3]. Considering the effects of microgravity are partially attributed to lack of mechanical force on bone tissue, which alters gene expression, reduction in transcription factors and growth factors. Furthermore, lack of gravity effects cell growth, proliferation, differentiation, cytoskeleton polymerization and cellular morphology [4, 5]. Thus to reverse these adverse effects on bone physiology, it is important to provide cells with mechanical stimulus which can provide essential mechanical signal for cells to counter the effects of microgravity. Ultrasound acoustic vibrations can be readily applied in, in vivo and human studies and has shown anabolic effects on osteopenic bone tissue [6]. Furthermore, ultrasound is a non-invasive and more target specific treatment relative to cyclic strain and vibration. The objective of this study is to see effects of low intensity pulsed ultrasound (LIPUS) on disused bone model and osteogenic activity of osteoblast cells cultures in simulated microgravity. This will help us understand that effects of ultrasound on microgravity and mechanotransduction pathway responsible for anabolic effect on bone cells.
Diabetes Alters Intracellular Calcium Transients in Cardiac Endothelial Cells
Authors: Sheikh Abdul Q. , Hurley Jennifer R. , Narmoneva Daria A.
Published: July 2013

Diabetic cardiomyopathy (DCM) is a serious diabetes-associated complication that results in myocardial dysfunction independent of other etiological factors [1]. Pathological alterations to the myocardium associated with DCM include circulatory defects, impaired heart muscle contraction, and abnormal calcium (Ca2+) homeostasis in cardiac cells[2]. In myocardium, endothelial cells play an essential role in maintaining intracellular Ca2+ hemostasis in response to stimuli and regulating cardiac function [3]. External stimulus may cause abrupt changes in Ca2+ balance, including Ca2+ release from sarco-endoplasmic reticulum (ER) [4]. Subsequent return of the Ca2+ level to basal levels occurs due to Ca2+ decay mechanism, which is mainly regulated by sarco-endoplasmic reticulum Ca2+ ATPase pumps (SERCA) present at ER membrane which are responsible for Ca2+ sequestration [5]. Studies have shown that the mechanisms by which Ca2+ homeostasis alters cardiac function in diabetic cardiomyocytes include reduced activity of the SERCA pumps [6]. However, no information is available regarding the effects of diabetes on Ca2+ hemostasis and the underlying Ca2+ sequestration mechanism in diabetic cardiac endothelial cells[7]. This study tested the hypothesis that diabetic endothelial cells will exhibit disruptions in Ca2+ decay kinetics via alterations in the sequestration mechanism.
Mesoscale Large Frequency-Range Characterization of the Elastic Modulus of Poly(Vinyl Alcohol) Hydrogel Using a Control-Integrated Indentation System
Authors: Wang Zhihua , O’Brien John , Shrotriya Pranav , Zou Qingze
Published: July 2013

Due to the desirable properties like biocompatibility and solubility in water, Poly (Vinyl Alcohol) (PVA) has been widely utilized in a broad range of areas including material research, biomedicine and pharmacy. Although its mechanical properties have been widely studied, few of the previous work has focused on its frequency dependent elastic modulus. In this paper, the frequency dependent elastic modulus of PVA samples (based on the physical crosslinking method) at mesoscale was investigated in experiments. An indentation system is designed and developed. And moreover, a recently-developed iterative-learning control technique is utilized to compensate for the hardware effect on the force-indentation measurement, and thereby, substantially increases the measurement frequency range. Then the Hertzian contact model is employed to obtain, from the measured force-indentation data, the elastic modulus of a PVA sample for the frequency range of 1 to 25 Hz.
A Combined In Vitro and In Silico Approach to Estimate the Molecular Arrangement Within a Fibronectin Fiber
Authors: Bradshaw Mark J. , Smith Michael L.
Published: July 2013

It has become apparent that the extracellular matrix (ECM) is a powerful modulator of cell behavior. Fibronectin (Fn) is of particular interest because it is a requisite cell adhesion molecule for development and wound healing and it is a promiscuous binding partner for many soluble signaling molecules. It was recently shown that the binding affinity of some molecules is dependent on the strain state of the Fn [2,3], reinvigorating our interest in the molecular mechanism of Fn fiber extension. The tertiary structure of the approximately 30 Fn type III domains of the protein has been shown to be capable of unfolding in single molecule force spectroscopy experiments, although evidence that unfolding occurs in Fn fibers has been indirect and has not been quantified. Nevertheless, unfolding of Fn molecules predicts a possible mechanism of strain dependant binding in Fn matrix and commensurate strain feedback to attached cells, contributing to the cellular mechanotransduction toolbox [3].
Nanofiber Micropatterns for Controlled Release of Biomolecules
Authors: Bonani Walter , Migliaresi Claudio , Tan Wei
Published: July 2013

Essential to growing or regenerating 3-dimensional tissues is the formation of functional microcirculation that provides nutrients, oxygen and signal molecules for tissue survival and function regeneration. In the past decade, molecule-based microvascular formation has been achieved in vitro and in vivo. However, direct delivery of angiogenic molecules often results in malformed hyperpermeable microvessels, microvessels with low density. This can be attributed to the lack of effective molecule mechanisms that regulate vascular formation. More recent studies utilize biodegradable materials to control the delivery of biomolecules for vascularization of engineered or ischemic tissues, and exciting results have shown the importance of molecule kinetics to the vascular formation. Molecule delivery mechanisms that mimic precisely-regulated spatiotemporal signaling events during natural vascularization may be a possible way to improve or optimize the process. Hence, this study is designed to develop a new release system capable of degrading in the body and releasing biomolecules in a spatiotemporally controlled manner.
Automated Diabetes Testing Device for the One-Armed/Disabled Patient
Authors: Abdallah Ali , Heid Brandon , Khan Hajra , Valikodath Nigil
Published: July 2013

We were approached by an amputee diabetic to build a device that could test blood sugar with the use of only one arm. Originally, this product was client based only. It was designed for an elderly diabetic amputee such that the device would allow him to single-handedly manage his blood glucose testing without any extra assistance from other persons. Although this was originally a client-specific device, it is expected to have a broader market based on the prevalence of arm amputations among the diabetic patient population. Statistics reveal that over 80,000 amputations are performed each year in the United States on people with diabetes. [1] The target audience is also intended for older individuals who suffer from having limited fine motor coordination due to conditions such as arthritis. Diabetic patients must test their glucose level several times a day, and therefore it is absolutely critical to have a glucose-testing device that allows a user to test his or her glucose-level with no trouble. This device would provide these diabetic patients with access to a more convenient and user-friendly system that would allow an individual to test his or her blood glucose level with ease.
A White Blood Cell Capturing Biochip Using a 3D Trapping Architecture
Authors: Tripathi Anurag , Chronis Nikos
Published: July 2013

White blood cells (WBCs) and their subtypes are important constituents of the human immune system as their concentration, quantified by a WBC count test, indicates the state of body’s immune response against infections. These cell count tests are important prognostic and diagnostic indicators for a number of human immunological diseases, most prominent of them being AIDS (1).
Biaxial and Failure Mechanical Properties of Passive Rat Middle Cerebral Arteries
Authors: Bell E. David , Kunjir Rahul S. , Monson Kenneth L.
Published: July 2013

Cerebral blood vessels are critical in maintaining the health and function of the brain, but their function can be disrupted by traumatic brain injury (TBI), which commonly includes damage to these vessels [1]. However, even in cases where there is not apparent mechanical damage to the cerebral vasculature, TBI can induce physiological disruptions that can lead to breakdown of the blood brain barrier or loss of cerebral autoregulation.
A Microfluidic Mixer to Activate Sperm Cells of Aquatic Species for Standardization of Computer-Assisted Motion Analysis
Authors: Park Daniel S. , Egnatchik Robert , Bordelon Hali , Tiersch Terrence R. , Monroe W. Todd
Published: July 2013

The objective of this paper is to develop a microfluidic device to: 1) activate a small volume of aquatic species sperm by rapid mixing with diluent, and 2) position sperm in a viewing chamber for motility evaluation using computer-assisted sperm analysis (CASA). Analysis of aquatic species sperm is becoming more important as the use of fish as biomedical models expands. Because it is more efficient to maintain frozen stocks of genetic material rather than thousands of research lines of adult fish, there has been increased study on cryopreservation for model fish. The analysis of fish gametes is challenging due to small sample size, short motility duration, and inconsistent activation (motility induction). For many aquatic species, sperm motility is initiated through the manual alteration of the medium osmolality, typically accomplished through manual dilution and mixing by hand. Manual methods limit control over the activation process and therefore viability analysis. The short lifespan of these cells makes CASA challenging due to the limitations in capturing and processing data rapidly enough to monitor the peak motility, as CASA systems were designed for mammalian sperm which have a longer motility duration.
Simulations of Flow Through Bileaflet Mechanical Heart Valves to Assess Platelet Damage
Authors: Yun B. Min , Wu Jingshu , Aidun Cyrus K. , Yoganathan Ajit P.
Published: July 2013

Prosthetic heart valves have been used for over 50 years to replace diseased native valves but still lead to severe complications such as hemolysis, platelet aggregation, and thromboembolic events. The most widely implanted design is the bileaflet mechanical heart valve (BMHV). Most modern BMHV designs have better flow hemodynamics and blood damage performance than their earlier-generation counterparts. However, blood element trauma and thromboembolic events still remain as major complications of current BMHV designs. These problems have been linked to blood element damage caused by non-physiological stresses. These stresses are caused by the complex flow fields that arise due to prosthetic heart valve design, particularly in the leaflet hinge region. In order to reduce the severity of these complications, the blood damage that occurs in flows through prosthetic heart valves must be well understood.
Hydraulic Resistance of a Novel Hollow-Core Microneedle Design
Authors: Hood R. L. , Kosoglu M. A. , Rylander C. G.
Published: July 2013

In recent years, developments in microscale fabrication have enabled the creation of needles on the scale of micrometers. These “microneedles” can be created out of a variety of materials and facilitate highly accurate small volume fluid delivery with minimal tissue disruption. Studies have shown that diameter and insertion force are primary determinants of patient pain caused by transdermal injection [1]. The small diameter of microneedles reduces the invasiveness and patient sensation associated with their clinical use. Microneedles have been used for enhancing skin permeability to drug delivery patches, transdermal infusion, and intrascleral inoculation [2–5].
A Non-Linear Model to Describe the Material Properties of Single Lamellae in the Human Annulus Fibrosus
Authors: Nagel Tina M. , Raghupathy Ramesh , Ellingson Arin M. , Nuckley David J. , Barocas Victor H.
Published: July 2013

Roughly three out of four people experience low back pain [1]. Causes are generally unknown, but low back pain is often attributed to intervertebral disc degeneration. To understand low back pain better, much research has focused on a fundamental understanding of the disc. Physiologically analogous material properties may support improved modeling and understanding of disease progression. Unfortunately, to date, few material property data have been collected in a realistic environment.
Mechanical Characteristics of Tissue Engineered Bone-Ligament-Bone Constructs Following ACL Replacement in Sheep
Authors: Ma J. , Smietana M. J. , Wojtys E. M. , Larkin L. M. , Arruda E. M.
Published: July 2013

With approximately 400,000 reported each year, anterior crucial ligament (ACL) injuries are the most common injury in the US. Unfortunately current ACL replacement strategies, which involve using either allografts from cadavers or autografts from patients’ own patellar tendons (PT) or hamstring tendons as a replacement, have several limitations including graft availability, risk of rejection, increased morbidity and, more importantly, unmatched intra-articular biomechanical properties of grafts and ACL. The objective of this study is to use self-assembling, scaffold-less bone-ligament-bone (BLB) engineered tissue constructs as grafts in a sheep ACL repair model to characterize the biomechanical behaviors of native ACL, PT, and tissue engineered ligament and subsequently present a viable option of using tissue engineered ligament graft for ACL repair.
Thrombus Initiation With Subsequent Growth Measured for Physiological Shear and High Pathological Shear
Authors: Bark David L. , Para Andrea N. , Ku David N.
Published: July 2013

Arterial thrombosis is often found near an atheroma in atherosclerotic disease, which can lead to acute myocardial infarction, i.e. a heart attack. Thrombus typically grows in regions of exposed subendothelium, which can exist when the plaque cap of the atheroma ruptures or erodes. The subendothelium creates an adherent surface to platelets and other thrombus constituents. Furthermore, an atheroma alters the normal physiological hemodynamics, which has been reported to correspond to local thrombus growth, despite equally adherent surfaces in undisturbed flow regions [1,2]. However, there has been some disagreement about which hemodynamics, specifically shear, may play the most influential role of localizing thrombus. Low shear and high shear have both resulted in thrombus growth [1,2]. Shear in the region of an atheroma can get over 100,000 s−1 [3].