bluuebunny/crossref_metadata_2025 huggingface dataset:
The Wall Shear Stress Vector: Methods for Characterising Truly Disturbed Flow
Authors: Peiffer Véronique , Weinberg Peter D. , Sherwin Spencer J.
Published: July 2013

Haemodynamic stresses acting on the arterial wall may play an important role in the initiation and development of atherosclerosis, and in particular are likely to explain its focal occurrence. Computational fluid dynamic (CFD) simulations of blood flow in arteries have been widely used to investigate this relation and a variety of metrics have been derived to link flow characteristics with lesion prevalence [1]. Although the initial focus was on the magnitude of the time-averaged wall shear stress (TAWSS), an oscillatory shear index (OSI) was subsequently introduced “to describe the shear stress acting in directions other than the direction of the temporal mean shear stress vector” [2]. Biological evidence suggests that flow without a definite direction, in contrast to shear with a clear direction (whether resulting from steady or pulsatile flow), causes sustained molecular signaling of pro-inflammatory and proliferative pathways [3]. Although the OSI has frequently been used to quantify the extent of disturbed flow, we emphasise that no singular metric can fully characterise the flow environment; in particular, we and other research groups [4] note that OSI and other similar metrics are unable to distinguish between simple uniaxial flows (which can be purely forward flowing or reversing) and multi-directional flows, which we term “truly disturbed”. We propose a new method that has this potential, and which complements existing metrics. The new method may help investigations of the importance of flow directionality.
Obstacle Detection and Avoidance Using Wavefront Planner and Kinect on a WMRA
Authors: Shindev Ivan , Marlin Shane , Preseault Nathan , Tamayo Rodrigo , Pence William , Alqasemi Redwan
Published: July 2013

Obstacle avoidance in autonomous navigation platforms is a well known problem that can be solved in numerous ways. This paper considers and analyzes the use of wavefront planner as an obstacle avoidance algorithm for a 9-DoF wheelchair-mounted robotic arm (WMRA) [1]. It also presents a suitable solution for obstacle detection using the OpenNI driver for interfacing with Microsoft’s Kinect. It further analyzes the capabilities of an autonomous operation of the WMRA and explains how this algorithm can be implemented into its navigation control. The results of this project showed that the Kinect can provide a very accurate representation of the surroundings. The wavefront planner can use this data to find a path from a start position to a goal without running into an obstacle.
Transcatheter Aortic Valves: A Finite Element Study of Leaflet Stress Distribution in the In Vivo Environment
Authors: Gunning Paul S. , Harewood Frank J. , Vaughan Ted J. , McNamara Laoise M.
Published: July 2013

The aortic valve is responsible for controlling the unidirectional flow of blood within the heart during the cardiac cycle [1]. Aortic stenosis reduces the opening area of the valve, impeding blood flow and can lead to increased strain on the heart muscle, onset of early fatigue and heart failure. The disease is prevalent in the elderly population and is predicted to affect 88.5 million people by 2050 [2]. Open heart surgery to replace stenotic valves with either bioprosthetic or mechanical surgical valves is the current gold standard of care. However 30% of patients presenting with stenosis are refused this highly invasive surgery because of high postoperative mortality rates in elderly patients or those with pre-existing illnesses [2]. Transcatheter Aortic Valves (TAV) are an alternative to conventional heart valve surgery [2, 3–4], which use minimally invasive techniques to replace stenotic valves. TAV’s consist of tissue leaflets on a self or balloon expandable percutaneous valve stent which is deployed via a transfemoral or transapical based approach. Owing to the fact that the first CE certification of a TAV (Edwards SAPIEN) was only in 2010 and received FDA approval for clinical trials in 2011, the long term performance of implanted TAV’s is as of yet unknown.
Loading-Induced Interstitial Fluid Flow in Bone Mechanobiology: An FSI Approach to the Osteocyte Environment
Authors: Verbruggen Stefaan W. , Vaughan Ted J. , McNamara Laoise M.
Published: July 2013

Bone is an adaptive material, which is particularly responsive to mechanical loading and can adapt its mass and structure to meet the mechanical demands experienced throughout life. The osteocyte, due to its ubiquitous presence throughout bone, is believed to act as the main sensor of mechanical stimulus in bone, recruiting other cells to control bone growth and resorption in response to changes in physiological demands. However the precise mechanical stimuli that osteocytes experience in vivo, and what type of stimulus instigates an adaptive response, are not fully understood.
CFD Challenge: Solutions Using the Commercial Finite Volume Solver, Fluent
Authors: Aristokleous Nicolas , Khozeymeh Mohammad Iman , Papaharilaou Yannis , Georgiou Georgios C. , Anayiotos Andreas S.
Published: July 2013

This work is a collaborative effort between the Biomechanics and Living System Analysis Laboratory (BIOLISYS) in Cyprus and the Biomechanics Laboratory of IACM/FORTH in Greece. Both labs combine interdisciplinary skills from engineering, medicine and biology to provide solutions to clinical problems associated with cardiovascular and other diseases. For this study, numerical flow simulations were performed using: a) open source software VMTK and commercial software ICEM CFD as pre-processors, b) the finite volume based solver Fluent and c) Tecplot 360 (Amtec Inc.) for post-processing.
Functional Imaging of Matrix Structure of Cryopreserved Engineered Tissues Using Back-Directional Gated Mesoscopic Imaging
Authors: Kim Young L. , Xu Zhengbin , Ozcelikkale Altug , Han Bumsoo
Published: July 2013

Successful cryopreservation of engineered tissues (ETs) can greatly advance the access and availability of cell/tissue engineering products for clinical use. One of the key challenges in cryopreserving ETs is that the functionality of ETs should be maintained throughout the preservation process. Many of the functionalities are associated with the extracellular matrix (ECM) microstructure, which in turn can be a crucial marker for the post-thaw functionality. Recent studies also reported that the ECM microstructure can be affected by freezing-induced cell-fluid-matrix interactions.1–3 Thus, it is critical to assess three-dimensional (3-D) matrix structure of cryopreserved ETs in a non-destructive, non-invasive, and rapid manner.
The Role of the Central Nervous System in the Integration of Proprioceptive Activity
Authors: Soltys Joseph S. , Wilson Sara E.
Published: July 2013

Vibration exposure has been known to have both negative and positive effects on human dynamics in a variety of clinical and occupational applications. Whole body vibration is known to be associated with low back pain and low back disorders [1]. It has been shown that whole body vibration and vibration of the lumbar musculature can result in loss of proprioceptive accuracy and delays in muscular response to sudden loading [24]. Conversely, vibration of the musculature has also been proposed as a means to improve the effects of training and exercise on strength and endurance [5–7]. Vibration has a number of known effects on proprioception in particular. These include kinesthetic illusions during vibration exposure [8] and altered proprioception post-vibration exposure [3, 9]. Understanding the neural pathways that contribute to these effects is important in better understanding the clinical and occupational implications of vibration exposure. Therefore, the objective of the current study was to examine brain activity using functional magnetic resonance imaging (fMRI) during a dynamic, proprioceptive task, both during and after vibration exposure in order to observe changes in activation that might contribute to these effects.
Simultaneous Measurement of Morphology and Traction Forces of Endothelial Cells Under Fluid Shear Stress
Authors: Ohashi Toshiro , Niida Yusaku , Tanaka Ryoichi , Sato Masaaki
Published: July 2013

Under fluid shear stress, vascular endothelial cells (ECs) cultured in a monolayer are known to exhibit marked elongation and orientation to the direction of flow [1]. It is also observed that intracellular F-actin filament distributions changed depending on the amplitude of shear stress and the direction of flow, suggesting morphology of ECs is closely related to cytoskeltal structure [2]. ECs generate contractile forces by the actin-myosin machinery and the forces are transmitted to underlying substrate as cellular traction forces. We hypothesize that reorganization of cytoskeletal structures regulates traction forces in ECs exposed to fluid shear stress. In order to measure traction forces and cell morphology simultaneously, we have developed a newly designed flow-imposed device in which a substrate with arrays of elastomeric micropillars (3 μm in diameter and 10 μm in height) is integrated on the bottom of a parallel plate flow chamber. In this study, traction force distributions and morphological changes in GFP-tagged ECs in a monolayer under fluid flow are simultaneously evaluated through image analysis in a spatial and a temporal manner.
Lower Macromer Concentration Enhances Nucleus Pulposus-Like Differentiation and Functional Extracellular Matrix Assembly by Human Marrow-Derived Stromal Cells Encapsulated in Photocrosslinked Carboxymethylcellulose Hydrogels
Authors: Gupta M. S. , Nicoll S. B.
Published: July 2013

Intervertebral disc (IVD) degeneration is associated with dehydration and loss of integrity of the nucleus pulposus (NP) region of the disc. The NP is a tissue comprised mainly of proteoglycans and type II collagen (COL II) [1]. Tissue engineering therapies could provide viable NP replacements as an alternative to current surgical procedures. Recently, photocrosslinked carboxymethylcellulose (CMC) hydrogels were shown to support cell viability and the assembly of functional extracellular matrix (ECM) by encapsulated human marrow-derived mesenchymal stromal cells (hMSCs) when cultured in serum-free, chemically defined medium with TGF-β3 [2]. Previous studies have shown that scaffold macromer density can influence functional mechanical properties and chondrogenic differentiation of several cells types in various hydrogel systems [3,4,5]. However, the impact of macromer concentration on hMSC differentiation in CMC hydrogels has not been evaluated. Therefore, the objective of this study was to examine the effects of CMC macromer concentration on NP-like differentiation and the elaboration of functional ECM in hMSC-laden CMC constructs.
Ulnar Collateral Ligament and Elbow Joint Loading During Throwing
Authors: Zheng Nigel , Wang Hongsheng , Eaton Koco
Published: July 2013

Ulnar collateral ligament (UCL) rupture is one of the most common throwing arm injuries for throwing athletes. Reconstructive surgery known as Tommy John surgery is often performed to restore joint stability [1]. According to the 2002 Major League Baseball Disability Analysis, almost 70% of players on the disabled list are pitchers and throwing arm related injuries account for 53% of all disabled list placements. To reach a high ball speed, pitchers cock, or excessively externally rotate their pitching arm to or near an extreme ROM of 180° [2]. The shoulder is then immediately internally rotated at over 7000°/s after the leading foot contact. The excessive external rotation ROM and astonishing internal rotation velocity are thought to contribute to throwing arm injury [3]. Repeated exposure to the large valgus torque may cause excessive laxity and catastrophic rupture of UCL [2]. A recent study showed that uninjured pitchers with higher elbow valgus torque exhibited UCL thickening whereas uninjured pitchers with lower elbow valgus torque did not have such adaptation in UCL appearance [4]. It is believed that microtear and catastrophic rupture of UCL are related to higher elbow valgus torque [2]. However, it is not clear how the conditions of the UCL are related to the elbow valgus torque during throwing. Therefore, it is our interest to investigate risk factors to throwing arm injuries. In this study, we investigated the elbow joint loading during throwing among subjects without UCL injury at the time of testing and after testing, with UCL reconstruction (UCL-R) at the time of testing, and UCL reconstruction after testing (PUCL-R). It was hypothesized that there was no significant differences in elbow joint loading between subjects with UCL-R, PUCL-R and uninjured groups. Findings from this may improve our understanding of UCL injury and assist us to identify risk factors for UCL injury.
Blood Flow Characterization in a Perfused Collagen Vessel Bioreactor Using X-Ray Micro-PIV
Authors: Voigt Elizabeth , Buchanan Cara F. , Rylander M. Nichole , Vlachos Pavlos
Published: July 2013

Newly developed cancer therapies must pass through a series of increasingly complex testing regimens before obtaining FDA approval as valid treatments. The costs of these tests increase rapidly as the physiological accuracy of the platform increases, from initial proof-of-concept in static tissue cultures, to treatment of animal models, and ultimately to human clinical trials. Three-dimensional engineered blood-perfused tumor models are becoming increasingly important as intermediate platforms for the study and treatment of cancer, as they are superior to static two-dimensional cultures in their reproduction of relevant physiological conditions and are inexpensive in comparison to animal models. Because of this, the design of well-characterized adaptable in vitro vascular tumor models has become a central objective of the emerging field of tumor engineering. Characterization of the flow within three-dimensional tumor models is critical for quantifying fluid shear stress and determining its role in pivotal tumor development processes such as tumor cell angiogenesis and metastasis. Ultimately, this knowledge will provide new avenues for therapeutic modulation of the tumor microenvironment.
Interactive Effect of Surface Tension and Viscosity on Displacement of Airway Mucus Inside a Rigid Model Adult Trachea During Cough
Authors: Ragavan Anpalaki J. , Evrensel Cahit A. , Krumpe Peter
Published: July 2013

Altered surface and viscoelastic properties of mucus during respiratory diseases have a strong influence on its clearance by cilia and cough. Combined effect of the surface tension and viscosity with relatively unchanged storage modulus of simulated airway mucus (simulant) considered as the capillary number on displacement of 0.3mL simulant aliquot during simulated cough through a model adult human trachea at relatively low cough velocity (15±0.5m/s) of 0.3s duration was investigated. Displacement of simulant aliquots decreased significantly with capillary number (p<0.0001). The interactive effects of viscosity and surface properties may give insight into understanding mucus displacement at low cough velocities in patients with chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF) and asthma.
Dynamic Tensile Loading Activates TGF and BMP Signaling in Mesenchymal Stem Cells on Aligned Nanofibrous Scaffolds
Authors: Heo Su-Jin , Driscoll Tristan P. , Mauck Robert L.
Published: July 2013

Mesenchymal stem cells (MSCs) are a promising cell source for tissue engineering applications, given their ease of isolation and multi-potential differentiation capacity [1]. External mechanical cues directly influence MSC lineage commitment [2]. However, it is not yet clear how these physical cues are transduced to the cell nucleus, an understanding of which may prove essential for orthopaedic tissue engineering. Transforming growth factor beta (TGFβ) and bone morphogenetic protein (BMP), members of the TGF beta superfamily, regulate cellular processes including growth and differentiation [3, 4]. TGF and/or BMP ligand binding initiate SMAD phosphorylation, translocation to the nucleus, and transcriptional activation of target genes [4]. Additionally, both ligands can influence the organization of chromatin and the Lamin A/C (LMAC) nucleoskeletal network [5]. For example, we have recently shown that TGF-β3 leads to corticalized LMAC, marked increases in heterochromatin (HTC), and increased nuclear stiffness [6]. Interestingly, dynamic tensile stretch of MSCs on aligned nanofibrous scaffolds, in the absence of these differentiation factors, resulted in many of these same nuclear transformations [6, 7]. The objective of this study was to identify how dynamic tensile stress is transduced in MSCs on aligned nanofibrous scaffolds, and further, to ascertain whether these mechanoregulatory changes are coordinated through TGFβ/BMP signaling pathways.
Correlation Among Hemodynamic and Morphological Metrics of Intracranial Aneurysms
Authors: Retarekar Rohini , Ramachandran Manasi , Madhavan Raghavan L.
Published: July 2013

There is increasing interest in assessing metrics of blood flow characteristics as prognostic indicators of rupture risk in intracranial aneurysms. Aneurysmal hemodynamics may be and has been quantified in the literature by numerous indices (about 18, to the best of our knowledge) each capturing some characteristic of flow. But are all these indices capturing unique characteristics of flow or are many of them redundant? And are they mainly proxies for basic morphological characteristics? Answering this question and identifying the indices that capture unique aspects of flow has practical implications to prospective studies designed to test the hemodynamics-rupture correlation. Lesser the number of indices, lesser will be the required sample sizes for sufficient statistical power. Alternatively, greater the number of indices, greater the likelihood that such studies will descend into an exercise in data mining. Further, understanding how these indices relate among themselves and to morphology can help us better reconcile findings from independent studies. The objectives of this study were to first document and categorize all reported indices in the literature and use a population of unruptured intracranial aneurysms to understand correlations among them and with morphological indices.
Quantifying Turbulent Wall Shear Stress in an Arteriovenous Graft Using Large Eddy Simulation
Authors: Browne L. D. , Griffin P. , Walsh M. T.
Published: July 2013

Hemodialysis patients require a vascular access capable of accommodating the high blood flow rates required for effective dialysis treatment. The arteriovenous graft is one such access. However, this access type suffers from reduced one year primary & secondary patency rates of 59–90% and 50–82% respectively [1]. The main contributor to the failure of this access is stenosis via the development of intimal hyperplasia (IH) that predominately occurs at the venous anastomosis. It is hypothesized that the resulting transitional to turbulent flow regime within the venous anastomosis contributes to the development of IH. The aim of this study is to investigate the influence of this transitional to turbulent behavior on wall shear stress within the venous anastomosis via the use of large eddy simulation.
Design of an In Vitro Migration Chamber for Quantifying the Homing Patterns of Parasitic Worms
Authors: Parsons Kevin D. , Kassis Timothy , Dixon J. Brandon
Published: July 2013

Lymphatic filariasis, a parasitic disease often resulting in severe lymphatic dysfunction and lymphedema, is perpetuated by an invasion of worms, delivered through mosquito bites, that reside, mature, and reproduce in the human lymphatic system. The disease cycle begins with stage 3 larvae (L3) leaving the mosquito and penetrating the dermal layer of the human while the mosquito is feeding where it eventually makes its way to a collecting lymphatic vessel where it resides for its adult life (up to 10 years) [1]. While many infected individuals will remain asymptomatic, a subset of patients will develop reconstruction of the tissue structure and the extreme swelling of the arms, legs, genitals and/or breasts. This elephantiasis occurs in over 10 million people worldwide and has a harsh negative effect on the infected individual’s ability to work and function in society.
Pore Formation in Schlemm’s Canal Endothelial Cells Is Mechano-Sensitive and Impaired in Glaucoma
Authors: Pedrigi Ryan M. , Gupta Ritika , Braakman Sietse T. , Stamer W. Daniel , Ethier C. Ross , Overby Darryl R.
Published: July 2013

Increased intraocular pressure (IOP) is the leading risk factor for glaucoma, but the mechanisms of IOP regulation during normalcy and disease are poorly understood. Considerable evidence suggests that Schlemm’s canal (SC) endothelial cells may influence IOP by regulating aqueous humor outflow via the formation of trans-endothelial pores. This study employs a biomimetic perfusion system to explore pore formation in SC cells in vitro. Our results show that pore formation increases with increasing pressure drop, occurs only when flow is directed basal-to-apical across the cell layer, and it is reduced in glaucomatous versus normal SC cell lines. These results suggest that pore formation is a biomechanically regulated process and they establish our system as the first in vitro model that captures a specific pathology associated with glaucoma.
Automated Generation of Tissue-Specific Finite Element Models Containing Ellipsoidal Cellular Inclusions
Authors: Bennetts Craig , Erdemir Ahmet
Published: July 2013

Microstructural cellular finite element (FE) models provide a means of describing tissue micromechanics and cell mechanobiology. For the cartilage, for example, the mechanical environment of chondrocytes has been explored with models such as those from the pioneering work of Guilak and Mow [1]. However, most cellular FE models typically include a single cell. These models do not provide the capacity to explore mechanobiological function and micromechanical effects caused by intercellular interactions. Therefore, it is desirable to develop models that more closely represent cell distribution and shape within the tissue of interest.
Influence of Compressive Pre-Stress on Backflow During Convection Enhanced Delivery in Hydrogel Tissue Phantoms
Authors: Casanova Fernando , Sarntinoranont Malisa
Published: July 2013

Convection enhance delivery (CED) is a local drug delivery technique for the treatment of neurological diseases. With CED, a needle (or cannula) is implanted into tissue and either a constant flow rate or pressure is applied to deliver infusate directly into the extracellular space. Under certain conditions, infusate flows back along the outer cannula wall in the space between the cannula and tissue instead of spreading out into tissue. Higher driving fluid pressures are often needed during CED and this can frequently result in backflow especially at high flow rates or with large needle diameters. Backflow is normally undesirable because specific targeting is not achieved, and drugs can reach regions of the brain where they are not effective, toxic, or result in unintended side effects. Previous models have been developed to predict backflow [1,2] that consider elastic expansion of tissue surrounding the needle due to infusion pressure. However compressive pre-stress between the tissue and the needle wall produced by tissues displaced during needle insertion has not been previously considered.
Role of Opening in the Mechanics of Shockwave Propagation Under Blast Loading Conditions
Authors: Gu Linxia , Akula Praveen , Ganpule Shailesh
Published: July 2013

A numerical study was performed to investigate the effect of ear openings on the dynamic brain response under blast loading condition. Transient nonlinear dynamic analysis of a cylindrical head was subjected to blast wave with a peak overpressure of 0.33 MPa and positive phase duration of 5 msec. The dynamic brain response is monitored in terms of intracranial pressures and shear stresses considering the opening in comparison to no opening case. The results have suggested increased intracranial pressures and shear stress in the brain with the presence of one opening. Furthermore, the opening also increased the fluctuation of stress wave through the skull with two times of increase in magnitude.
Validation of a Novel Microscale Mold Patterning Protocol Based on Gelatin Methacrylate Photopolymerizable Hydrogels
Authors: Occhetta Paola , Sadr Nasser , Piraino Francesco , Redaelli Alberto , Moretti Matteo , Rasponi Marco
Published: July 2013

Native tissues are composed of functional three-dimensional (3D) units on the scale of 100–1000μm. The 3D architecture of these repeating units underlies the coordination of multicellular processes such as proliferation, differentiation, migration and apoptosis[1]. The requirement for 3D biomimetic matrices to mimic in vitro the ECM microarchitecture found in vivo becomes relevant in complex and vascularized tissue engineered models[2]. Among others, photopolymerizable hydrogels offer tunable geometrical features similar to the macromolecular-based components of soft ECM [3], can be crosslinked either in vivo or in vitro in the presence of a photoinitiator agent (PI) using visible or ultraviolet (UV) light irradiation, and have shown good compatibility with several protocols for cell embedding at different size-scales. In the present study, a new protocol to obtain cell-laden hydrogel micropatterns with highly controlled geometrical features is presented, based on the combination of polydimethylsiloxane (PDMS) replica molding and UV photopolimerization of methacrylate gelatin (GelMA).
Mechanics of Electrospun Scaffolds: An Application to Heart Valve Tissue Engineering
Authors: Argento G. , Simonet M. , Oomens C. W. J. , Baaijens F. P. T.
Published: July 2013

In the last decade electrospinning has shown its potential of being a feasible technique to manufacture scaffolds for tissue engineering [1]. Previous studies observed that, on a micrometer scale, the topology of the scaffold plays a fundamental role in the spreading and the differentiation of the cells [2], and in the growth of neo-extracellular matrix. On a tissue scale (in the order of cm) the stiffness of the construct enables the possibility of applying mechanical cues for the development of a functional engineered tissue [3]. Studies on scaffold mechanics based on volume-averaging theory succeeded in demonstrating that the arrangement of the micro-scale scaffold components influences the macro-scale mechanical behavior [4].
Quantifying the Biomechanics of the Embryonic Zebrafish Heart
Authors: Johnson Brennan M. , Garrity Deborah M. , Dasi Lakshmi P.
Published: July 2013

Congenital heart defects are present in 4 to 50 per 1000 live births[1]. Most of these defects begin within the first few weeks post fertilization. Ample evidence exists which shows that mechanical epigenetic factors, such as pressure and shear stress, play key roles in heart development [2–3]. It has been shown in-vitro that cardiomyocytes are able to sense and respond to the presence of pulsatile flow[4], and that shear stress can activate genetic pathways which might ultimately dictate the morphological development of the cardiac tissue[5]. When blood flow characteristics have been changed experimentally, embryonic hearts consistently develop serious malformations. In order to understand mechanical epigenetic factors and their role in heart development, it is critical to contrive techniques for quantitatively measuring the biomechanics of the embryonic heart.
The Role of Ankle Plantarflexors in Maintaining Dynamic Balance During Human Walking
Authors: Neptune Richard R. , McGowan Craig P. , Hall Allison L.
Published: July 2013

The regulation of whole-body angular momentum is essential for maintaining dynamic balance during human walking and appears to be tightly controlled during normal and pathological movement (e.g., [1, 2]). The primary mechanism to regulate angular momentum is muscle force generation, which accelerates the body segments and generates ground reaction forces that alter angular momentum about the body’s center-of-mass to restore and maintain dynamic balance. Previous modeling studies have shown the ankle plantarflexors are important contributors to the anterior/posterior, vertical and medial/lateral ground reaction forces during human walking [3, 4], and therefore appear critical to regulating angular momentum and maintaining dynamic balance during walking.
Effect of Blood Pressure on Closing Dynamics of Bileaflet Mechanical Heart Valves
Authors: Forleo Marcio H. , Johnson Brennan M. , Dasi Lakshmi P.
Published: July 2013

Implantation of a bileaflet mechanical heart valve (BMHV) continues to be associated with a risk of thromboembolic complications despite anti-coagulation therapy1. This has been attributed to the structurally rigid design of the leaflets and valve mechanics combined with an intricate hinge mechanism for the rigid leaflets. The lack of a built in compliance within the valve mechanics presumably leads to sharp stress gradients within the flow as well as a violent closure of the valve often associated with the audible impact of the leaflets to the housing, and a potential for momentary cavitation of blood in the wake of leaflet impact.
Surface Parameterization of an Abdominal Aortic Aneurysm to Characterize Geometrical Evolution During Longitudinal Study of Patients
Authors: Dupay A. , Snyder P. , Lee W. , Baek S.
Published: July 2013

For an abdominal aortic aneurysm (AAA) in vivo there are multiple tissues contacting its boundary, none of which have been fully considered for their effect throughout disease progression. Trends such as arterial asymmetry, surface curvature flattening, and arterial tortuosity could be significantly influenced by both surrounding tissue and hemodynamic factors. In order to quantify either the combined or separate influence of such factors during disease progression a precise characterization of aneurysm geometry evolution is needed. Multiple methods for geometrical parameterization of abdominal aortic aneurysms (AAAs) have been previously developed using isolated patient CT scan data but the focus has been mainly on the association of such geometrical parameters with the rupture risk and the efficacy of the parameterization is not fully investigated for a longitudinal study yet (multiple CT scans per patient at progressive intervals) [1]. For this study we have produced a series of 3D models for AAAs in longitudinal studies, developed an arterial centerline generation algorithm, and automated a geometric parameterization procedure for the arterial surfaces. It should be noted that the caliber of our collection of data is relatively rare as it is high resolution, features many patients, and on average has 4–5 images per patient.
Collagen Network Architecture Varies Between Pure Collagen and Collagen-Fibrin Co-Gels
Authors: Lai Victor K. , Kerandi Allan M. , Lake Spencer P. , Tranquillo Robert T. , Barocas Victor H.
Published: July 2013

Naturally-occurring extracellular matrix (ECM) proteins, e.g. collagen I and fibrin, play an important role in tissues, conferring structural integrity and providing a biochemical environment for eliciting important cellular responses (e.g. migration). Tissue engineers use a variety of matrix polymers as initial scaffolds for seeding cells, sometimes in combination with one another (e.g. collagen-fibrin [1]). For example, our group fabricates arterial tissue equivalents (TEs) by seeding cells in a fibrin gel, which is gradually degraded over time and replaced by cell-produced collagen [2]. While the structure and mechanics of individual ECM proteins have been studied extensively, how multiple fibrillar networks interact to confer overall mechanical behavior remains poorly understood. Narrowing this gap in knowledge of scaffolds comprising multiple fibril networks is crucial in allowing for more rational design in tissue engineering, as cells react differently according to their mechanical environments. For collagen-fibrin networks in particular, early efforts in elucidating interactions between these two fibril networks in co-gels have proven inconclusive due to inconsistent findings from various groups. Recent modeling efforts by our group have shown that simple “series” and “parallel” type interactions provide bounds for the mechanical behavior of collagen-fibrin co-gels [3]. In addition, experiments on pure collagen and fibrin vs. their respective networks from collagen-fibrin co-gels after digestion showed slight differences in mechanical behavior [4]. These previous studies have focused on the composition-function relationship between collagen and fibrin. The objective of the current work is to explore how collagen network architecture changes in the presence of the fibrin network in collagen-fibrin co-gels, thereby providing an added dimension to our understanding of collagen-fibrin systems by elucidating structure-composition-function relationships between collagen and fibrin.
Design of a Bioreactor for Mechanical Stimulation of Adipose Derived Stem Cells for Intervertebral Disc Tissue Engineering
Authors: Cleary Heather , Barkley Thomas , Goodman Adam , Payne Michael , Virtue John , Vernengo Jennifer , Kadlowec Jennifer
Published: July 2013

Lower back pain is one of the most common medical problems in the world [1], affecting between 70% and 85% of the US population at some point during their lives [2]. Disc degeneration is caused by biological changes in the disc, which result in dehydration of the nucleus pulposus (NP). The long term goal of this project is to treat disc degeneration with a tissue engineering strategy for the regeneration of the nucleus pulposus using messechymal stem cells derived from adipose tissue. It has been established in cartilage regeneration studies that cyclic compressive loading of stem cells is beneficial for tissue formation compared to static culture [3–7]. In this work, a bioreactor is being developed that can subject cell-seeded polymeric tissue engineering scaffolds to dynamic compressive forces. Ultimately, the bioreactor will be used to study the effects of different loading parameters on the production of new nucleus pulposus tissue from adipose-derived stem cells.
Musculoskeletal Model of the Human Knee With Representation of Menisci During the Stance Phase of a Walk Cycle
Authors: Kia Mohammad , Guess Trent M. , Stylianou Antonis
Published: July 2013

Movement simulation and musculoskeletal modeling can predict muscle forces, but current methods are hindered by simplified representations of joint structures. Simulations that incorporate muscle forces, an anatomical representation of the natural knee, and contact mechanics would be a powerful tool in orthopedics. This study combined a validated anatomical model of a knee joint with menisci and a musculoskeletal model of the human lower extremity. A forward-dynamics muscle driven simulation of the stance phase of a walk cycle was simulated in LifeMOD (Lifemodeler, Inc) and muscle forces and ground reaction forces were estimated. The predicted forces were evaluated using test data provided by Vaughan CL. et al. (1999).
Combined Effects of Nanofiber Matrix Elasticity and VEGF-A on the Differentiation of Mesenchymal Stem Cells Towards Mature Endothelial Cells
Authors: Wingate Kathryn , Tan Yan , Nemenoff Raphael , Tan Wei
Published: July 2013

The potential of mesenchymal stem cell (MSC) in the treatment of vascular diseases is becoming increasingly recognized.[1] The use of MSC to produce a functional endothelium in synthetic vascular grafts is of particular interest as this would prevent common graft failures such as neointima hyperplasia and thrombus. Current attempts to produce a functional endothelial layer with endothelial cells (EC) have limited success due to the need for invasive surgery and the limited expansion capability these cells have in vitro.[2] MSC are a powerful cellular alternative as they are easily obtained through a bone marrow biopsy, have a large expansion capability in vitro, are multipotent, and thromboresistant. Individual factors such as matrix elasticity, matrix structure, growth factors, and mechanical stimulations have all been shown to contribute to MSC differentiation towards vascular phenotypes in vivo. However, the response of MSCs to the combined effects of these factors is not well characterized. Additionally, many experiments studying MSC differentiation are conducted on 2D substrates instead of simulating the 3D nanofiber matrix structure found in-vivo. Furthermore, little is known about the underlying cell signaling pathways that direct vascular differentiation. Currently, researchers have yet to achieve MSC differentiation into mature, functional endothelial cells, a critical step for regenerating healthy vascular tissue. We hypothesize that the combined effects of VEGF-A growth factor and a 3D matrix elasticity that mimicking the mechanochemical properties of in-vivo intima induce more complete MSC differentiation into EC expressing mature markers through the regulation of critical vascular signaling molecules such as MAPK/ERK and RhoA/Rock.
Combining Clinical Neuroimaging and Real-World Impact Data to Investigate Motor Vehicle Crash-Related Subarachnoid Hemorrhage
Authors: Urban Jillian E. , Whitlow Christopher T. , Maldjian Joseph A. , Powers Alexander K. , Stitzel Joel D.
Published: July 2013

Approximately 1.7 million people sustain a traumatic brain injury (TBI) each year, with motor vehicle crash (MVC) representing the leading cause for hospitalization. Subarachnoid hemorrhage (SAH) is the most common AIS 3+ injury resulting from MVC-related trauma. Little is known, however, about the relationship between specific crash parameters and resulting intracranial trauma. Yoganandan et al performed a study of 132 occupants with severe-to-fatal head injuries, showing that direct contact loading of the head results in a high percentage of occupants with brain injury with the most frequent contact being the pillars[1]. A study by Morris et al showed almost one-quarter of severe head injuries occur due to contact with an interior vehicle structure. Additionally, injuries that are more diffuse in nature occur with an interior contact within the vehicle[2]. In this study, SAH volume in addition to total injured volume of the brain was analyzed in order to better understand occupant injury, with the hypothesis that these traumatic neuroimaging findings would correlate with specific crash parameters.
Direct Measurement of Human Cervical Tissue Permeability
Authors: Fernandez Michael , Vink Joy , Wapner Ronald , Yoshida Kyoko , Myers Kristin M.
Published: July 2013

The mechanical integrity of the uterine cervix is critical for the full-term success of a pregnancy. It must be strong to retain the fetus throughout gestation and then undergo a remodeling and softening process before labor to allow dilation and delivery. We hypothesize that the preterm birth (PTB) condition known as cervical insufficiency (CI) is related to a weak or soft cervix. Such PTBs are responsible for infant developmental problems and in severe cases, infant mortality. To understand the etiologies of CI, our overall research goal is to investigate the mechanical behavior of the cervix. As a foundation for future in-vivo tools to assess cervical softness, we aim to quantify cervical structure-material property relationships for nonpregnant (NP) and pregnant (PG) tissue from women with different obstetric backgrounds, including women with a previous history of CI. The goal of this study is to characterize cervical tissue as a poroelastic (biphasic) material. Here we present the results of two mechanical experiments on NP and PG hysterectomy cervical tissue samples: first, confined compression and second, direct measurement of permeability by a custom strain-adjustable permeation rig.
Effect of Flow Pulsatility on Modeling the Total Cavopulmonary Hemodynamics: A Numerical Investigation
Authors: Khiabani Reza H. , Restrepo Maria , Tang Elaine , De Zélicourt Diane , Fogel Mark , Yoganathan Ajit P.
Published: July 2013

Single Ventricle Heart Defects (SVHD) are present in 2 per 1000 live births in the US. SVHD are characterized by cyanotic mixing between the de-oxygenated blood from the systemic circulation return and the oxygenated blood from the pulmonary arteries. Palliative surgical repairs (Fontan procedure) are performed to bypass the right ventricle in these patients. In current practice, the surgical interventions commonly result in the total cavopulmonary connection (TCPC). In this configuration the systemic venous returns (inferior vena cava, IVC, and superior vena cava, SVC) are directly routed to the right and left pulmonary arteries (RPA and LPA), bypassing the right heart. The resulting anatomy has complex and unsteady hemodynamics characterized by flow mixing and flow separation. Pulsation of the inlet venous flow during a cardiac cycle results in complex and unsteady flow patterns in the TCPC. Although various degrees of pulsatility have been observed in vivo, non-pulsatile (time-averaged) flow boundary conditions have traditionally been assumed in modeling TCPC hemodynamics, and only recently have pulsatile conditions been incorporated without completely characterizing their effect or importance. In this study, 3D numerical simulations were performed to predict TCPC hemodynamics with both pulsatile and non-pulsatile boundary conditions and to investigate the accuracy of applying non-pulsatile boundary conditions. Flow structures, energy dissipation rate and pressure drop were compared under rest and estimated exercise conditions. The results show that TCPC hemodynamics can be strongly influenced by the presence of pulsatile flow. However, there exists a minimum pulsatility threshold, identified by defining a weighted pulsatility index (wPI), above which the influence is significant.
Integration of Microstructural Architecture of the Mitral Valve Into an Anatomically Accurate Finite Element Mesh
Authors: Amini Rouzbeh , van Loosdregt Inge , Koomalsingh Kevin , Gorman Robert C. , Gorman Joseph H. , Sacks Michael S.
Published: July 2013

Although mitral valve (MV) repair initially restores normal leaflets coaptation and stops MV regurgitation, in long term it can also dramatically change the leaflet geometry and stress distribution that may be in part responsible for limited repair durability. As shown for other collagenous tissues, such changes in geometry and loading reorganize the fiber architecture. In addition, MV interstitial cells respond to the altered stress by undergoing alterations in biosynthetic function, which would affect the load-bearing capabilities of MV and its long-term durability. Thus, investigating the repair-induced MV stress and the concomitant microstructural alterations is a key step in assessing the repaired valve durability. Finite element models have been widely used for stress analysis of the mitral valve [1–3]. Most of these models, however, have employed only basic constitutive models and utilized simplified valve geometry. Above all, they have ignored the complex microstructure of the MV, which is the critical physical link between organ level stresses and cellular function. Thus, in this work we developed an initial method to develop an accurate geometrical model of the ovine MV and map the fiber structure for the purposes of developing high fidelity computational meshes of the MV.
Tissue- and Cell-Level Inhomogeneities Significantly Alter the Mechanical Behavior of Tissue-Engineered Cartilage
Authors: Khoshgoftar M. , Wilson W. , Ito K. , van Donkelaar C. C.
Published: July 2013

The insufficient load-bearing capacity of today’s tissue engineered (TE) cartilage is an important limiting factor for its clinical application. It is believed that the mechanical quality of TE cartilage constructs would be optimal if it had both a structure and composition resembling native cartilage. Cartilage TE studies therefore aim to reach extracellular matrix (ECM) content that resembles that of native tissue. However, the correlation between ECM content and mechanical properties of TE constructs is not unique and the correlation between matrix content and mechanical properties vary considerably.
Cellular Membrane Tether Retraction: Experiment and Model
Authors: Shao Jin-Yu , Liu Baoyu
Published: July 2013

During leukocyte rolling on the endothelium, membrane tethers can be extracted simultaneously from both leukocytes and endothelial cells because of the force imposed by the blood flow [1]. Tether extraction has been shown to stabilize leukocyte rolling by increasing the lifetime of the adhesive selectin-ligand bonds that mediate leukocyte rolling [2]. Over the past two decades, tether extraction has been studied extensively, both experimentally and theoretically. In contrast, much less is known about tether retraction.
Reduced Compliance in Patellar Tendons From a Mouse Model of Muscular Dystrophy
Authors: Wagner Hallie , Lowe Dawn , Barocas Victor
Published: July 2013

Muscular dystrophies are degenerative diseases that affect primarily skeletal muscles. Most studies of muscular dystrophy focus on muscles, but tendons are an important part of the musculotendon complex that transmits forces from muscles to bones. As the disease progresses, tendon shortening occurs, and some patients require tendon release or cord lengthening surgery to increase tendon length [1]. Despite the prevalence of these surgeries, very little is known about the mechanical properties of tendons in muscular dystrophy patients, or how they change as the tendon remodels or compensate in response to muscle degeneration.
Flow Modification of Cerebral Aneurysm by Flow Diverter (Pipeline) With Different Packing Densities
Authors: Xiang Jianping , Ma Ding , Siddiqui Adnan , Meng Hui
Published: July 2013

Flow diverter, a braided fine mesh stent, is emerging as a novel device to treat wide-necked, fusiform, and giant cerebral aneurysms since these types of aneurysms are either untreatable otherwise or have high recurrence rate treated by endovascular coils. Flow diverter devices represent a major paradigm shift in the endovascular treatment of aneurysms from filling the aneurysm cavity to diverting blood flow away from aneurysm sac with parent vessel reconstruction. Due to its high flexibility, a flow diverter can be manipulated during deployment process to achieve better results; for example, an experienced neuro-interventionalist can manipulate the stent’s local metal coverage through coordinated movement of catheter pull-back, pusher advancement, and distal coil release to pack higher density for the aneurysm orifice region to divert more flow away from aneurysm, making aneurismal thrombosis quicker and easier. Pipeline embolization device is the first flow diverter approved by FDA. In this study, we investigate the flow modification of a wide-necked aneurysm by Pipeline with different packing densities.
Potential Hemodynamic Mechanisms for Gender Differences in AAA Formation
Authors: Smolensky Alexander V. , Clement Stephanie , Passerini Tiziano , Piccinelli Marina , Veneziani Alessandro , Oshinski John N. , Taylor W. Robert
Published: July 2013

Abdominal aortic aneurysms (AAA) are a major cause of morbidity and mortality in the US. It is classically thought of as a disease of older men with the incidence approaching 30%. The most common place of AAA is infrarenal abdominal aorta where oscillatory shear stress (OSS) is present. OSS is known to initiate an inflammatory response in the endothelium. It is also known that females are at lower risk for developing AAA. The explanation for this difference is lacking. We recruited 8 healthy volunteers, 4 males and 4 females who underwent infrarenal abdominal aortic Magnetic Resonance angiography and phase contrast imaging. The collected data was used to calculate systolic forward and diastolic retrograde blood flow. Our results suggest that female infrarenal aortas are exposed to a 3-fold lower degree of OSS. It appears that the low resistance internal iliac arterial system may be in part responsible for such flow patterns. We conclude that female aortas are subjected to lower OSS and that low resistance internal iliac arterial system appears to play a protective role.