bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantification of Nanostructure Distribution in Tissue Using MicroCT Imaging
Authors: Attaluri Anilchandra , Manuchehrabadi Navid , Dechaumphai Anna , Ma Ronghui , Zhu Liang
Published: July 2013

Recently, two nanotechnologies have emerged as promising hyperthermia therapies due to their ability to confine adequate thermal energy in tumors. Both overcome the limitations of traditional hyperthermia approaches such as microwave and ultrasound, which have short penetration depths into tissue and often cause collateral thermal damage to the superficial tissue layers. One uses magnetic nanoparticles to generate heat when the nanoparticles are subject to an alternating magnetic field [1–2]. The other one uses gold nanoshells or nanorods in laser induced photothermal therapy [3–4]. By varying the geometric ratio, the nanostructures can be tuned to have strong absorption and scattering to a specific laser wavelength. The enhancement in laser energy absorption would confine the laser energy in a tumor area congregating by the nanostructure. The efficacy of these two methods relies on the achieved tumor temperature elevations which are largely determined by the nanostructure concentration distribution in the tumor. Therefore, having an imaging technique to directly visualize and analyze the three-dimensional nanostructure distribution in tumors would greatly improve treatment protocols to kill all tumor cells while avoiding overheating in the surrounding healthy tissue.
In Vivo Actuation System for Mechanostimulation of Large Wound Healing
Authors: Gurkan Umut Atakan , Dubikovsky Alexandra , Freeman Lynetta J. , Snyder Paul W. , Meldrum Russell D. , Akkus Ozan
Published: July 2013

The incidence of large open wounds in the US is estimated to be about 5–7 million per year which results in a cost of greater than $20 billion for wound management [1]. Large open wounds occur due to burns, trauma, and secondary to surgical interventions, ulcers or pressure sores. The current clinical practice is to treat large open wounds by delayed primary closure where skin is stretched under constant tension to approximate wound edges by relying on the extensibility of the neighboring skin, by skin grafting or by managing the wound to heal by second intention. Delayed primary closure is inapplicable when the strength of the skin is compromised (e.g. age, diabetes). Furthermore, delayed primary closure usually leads to excessive wound tension which introduces hypertrophic scars [2] and ischemia [3] to the skin and the underlying muscles. Skin autografts may result in morbidity of the donor site. Therefore, there is the need for noninvasive methods which will enable large wound closure in a reasonable time frame with minimal scar formation while alleviating or reducing the need for skin graft harvest.
Collagen Orientation in the Anterior Mitral Valve Leaflet
Authors: Shultz Tyler , Rauch Manuel , Kuhl Ellen
Published: July 2013

The Mitral Valve (MV) serves to ensure unidirectional blood flow from the pulmonary to systemic circulation. When the MV fails to function correctly, backflow from the left ventricle to left atrium occurs during heart contraction. This condition is called Mitral Valve Regurgitation (MVR) and is estimated to affect 2 to 2.5 million people in the United States alone [1]. Surgical techniques exist to repair MVR, and each affects the structure of the valve in a different way [2]. As the main load-bearing structure in the leaflets, collagen fibers have a tremendous impact on how the leaflets are able to support pressure loads, and their orientation has great functional implications. The goal of this study is therefore to investigate the microstructure of mitral valve tissue. Since collagen makes up approximately 60% of the dry weight of the leaflet [3], we focused our study on this macromolecule. In a complementary in-vivo study, we computed mitral leaflet strains in radial and circumferential direction using a continuum mechanical approach based on the 4D coordinates of 23 radiopaque markers sewn onto the anterior MV leaflet [4]. Results shown in Figure 1. As clearly seen from the figure, strains exhibit pronounced anisotropy. We expect that comparison of the collagen orientation in the leaflet with the these strain profiles will enhance our knowledge of the role of collagen in MV mechanics and the effect that potential surgical interventions may have on MV functionality. While collagen orientation has been determined using Small Angle Light Scattering [5], Polarized Light Microscopy [5], and X-ray Diffraction [6], histological methods to characterize the collagen orientation over the entire leaflet have not been reported. Therefore, we will study the orientation of collagen throughout the anterior ovine MV leaflet using tissue histology.
A Particle Image Velocimetry Study of the Penn State 50cc Left Ventricular Assist Device: The Impact of Varying Heart Rate
Authors: Navitsky Michael A. , Nanna Jason C. , Topper Stephen R. , Deutsch Steven , Manning Keefe B.
Published: July 2013

Approximately 5.7 million Americans are afflicted with heart failure, with a reported 670,000 new diagnoses each year [1]. Left ventricular assist devices (LVADs) function as a bridge to transplant therapy for advanced staged heart failure patients awaiting a donor heart. A pulsatile 50cc LVAD, Figure 1, is currently under development for cardiac support of patients with limited chest cavity size. Although the 50cc LVAD is functional in assisting a failing ventricle, complications such as thrombus formation may limit long term usage.
Quantifying the Effects of Extracellular Conductivity on Transport During Electroporation
Authors: Sadik Mohamed M. , Li Jianbo , Shan Jerry W. , Shreiber David I. , Lin Hao
Published: July 2013

Electroporation is an effective means to permeabilize the cell membrane and deliver biologically active molecules (such DNA, RNA, dyes, etc…) into the cell cytoplasm, while maintaining cell viability and functionality [1]. Despite extensive research, electroporation still suffers from major drawbacks such as high cell death and low delivery efficiency. In the past, studies focused mainly on permeabilization of the membrane during electroporation while transport of molecules from one side of the membrane to the other has been overlooked. Previous experimental work demonstrated an inverse relation between the electrical conductivity of the extracellular buffer and total concentration delivered into cells [2]. This inverse correlation suggests that additional molecular transport mechanisms, besides diffusion, govern the delivery into cells.
Intercellular Junctions Play an Important Role in Orientation of Vascular Endothelial Cells Exposed to Cyclic Stretch
Authors: Huang Wenjing , Sakamoto Naoya , Hanamura Kazuhiko , Miyazawa Ryotaro , Sato Masaaki
Published: July 2013

Endothelial cells (ECs) undergoing cyclic stretch align perpendicularly to the stretch direction [1]. Phosphorylation of focal adhesion kinase (FAK), an important component of focal adhesion (FA) signaling pathways, is thought to be required for the stretch-dependent morphological response of ECs [1]. However, since it has been reported that FAK is not always required for EC response to cyclic stretch is regulated by multiple signal transduction pathways in ECs.
Effects of Lymphangion Subdivision in a Numerical Model of a Lymphatic Vessel
Authors: Bertram Christopher D. , Macaskill Charles , Moore James E.
Published: July 2013

We have recently reported development of a lumped-parameter model for several lymphangions in series [1]. The model provides for both active smooth muscle contraction (intrinsic pumping) and passive compression of the lymphatic by external tissues (extrinsic pumping). The valves which define the lymphangions vary their resistance sigmoidally, having a high (low) resistance for an adverse (favorable) pressure difference. With no refractory period between sinusoidal active tension episodes, maximum pumping efficiency was reached when each lymphangion contracted 135° after that immediately upstream; simultaneous contraction (corresponding to the situation of extrinsic pumping) was especially inefficient.
On the Use of In Vivo Measured Flow Rates as Boundary Conditions for Image-Based Hemodynamic Models of the Human Aorta
Authors: Gallo Diego , De Santis Gianluca , Negri Federica , Tresoldi Daniele , Rizzo Giovanna , Ponzini Raffaele , Massai Diana , Deriu Marco , Cadioli Marcello , Verhegghe Benedict , Segers Patrick , Redaelli Alberto , Morbiducci Umberto
Published: July 2013

It has been demonstrated that computational fluid dynamics (CFD) have the potential to enhance the comprehension of the role played by hemodynamic factors involved in atherosclerosis. Recently, phase-contrast magnetic resonance imaging (PC-MRI) has emerged as an effective tool for providing accurate vascular geometries for CFD simulations and quantitative data on blood flow rates, which can be used to specify realistic boundary conditions (BCs). However, the application of acquired flow waveforms at boundaries is not straightforward, mainly (i) due to possible occurrences of phase shifts and attenuations of outflow with respect to inflow rate and (ii) due to the instantaneous mass conservation constraint, which is required in hemodynamic simulations with rigid wall models, but is not guaranteed in in vivo measurements. As an alternative, new boundary conditions schemes have been developed in an effort to consider the interaction between the computational domain and the upstream/downstream vasculature by coupling through-scale hemodynamic models [1]. However, the identification of the parameters of these simplified vascular models on a subject-specific base involves both pressure and flow rates measurements [2]. In this context, it is clear that the direct application of individual PC-MRI measured flow rates waveforms as BCs in patient-specific simulations should be preferred [3]. In order to overcome the limitations mentioned above, measured flow rates should be combined with stress-free conditions or fixed mass flow ratio (derived from the same set of PC-MRI data) between inlet and multiple outlet sections. However, prescribing different BCs at boundaries can affect the solutions of the equations governing blood flow [1]. For this reason, different strategies in combining outlet BCs could lead to different simulated hemodynamics. This work analyzes the influence of different possible strategies of applying PC-MRI measured flow rates on an image-based hemodynamic model of a healthy human aortic arch with supra-aortic vessels. A total of six flow simulations was carried out applying six different schemes for treating BCs at outlets. Three common wall shear stress (WSS)-based indicators of abnormal flow were considered and the sensitivity of these indicators to the outlet treatment strategy was evaluated.
Cell-to-Cell Variability in Tensile Strains Occurring in the Plasma Membrane and Nuclear Surface Area of Compressed Myoblasts
Authors: Slomka Noa , Gefen Amit
Published: July 2013

Confocal-microscopy-based three-dimensional (3D) cell-specific finite element (FE) modeling has recently been introduced by our group as a method to simulate the structural behavior of realistic cell geometries under external loading, while considering details of intracellular organelle [1,2]. This method provides comprehensive knowledge regarding cellular mechanics problems, for example, it is useful in the context of understanding the aetiology of deep tissue injury (DTI) — a type of a serious pressure ulcer associated with sustained cellular deformations [3–6]. In this regard, we previously postulated that sustained deformations of soft tissues near bony prominences could cause cell death by a mechanism of locally stretching cells, the consequence of which being that the permeability of the plasma membrane and nuclear surface area (NSA) in the affected cells increases. This, in turn, pathologically changes cell-matrix and intracellular transport profiles and eventually disrupts cellular homeostasis [1,7]. We hypothesize that tensile strains in the plasma membrane and NSA might differ in magnitude and pattern across externally-loaded individual cells of the same cell type, due to cell-to-cell morphological differences. Hence, in this study, we utilize confocal-based cell-specific 3D modeling to analyze tensile strain states in the plasma membrane and NSA of 3 different skeletal muscle cells (myoblasts) subjected to compression. We were specifically interested in chacterizing cell-to-cell variability in magnitudes and patterns of the localized strains.
Simulating Metal Implants in Full Thickness Cartilage Defects
Authors: Manda Krishnagoud , Eriksson Anders
Published: July 2013

Damage or degeneration in the articular cartilage is a major problem that affects millions of people in the world. The biomechanical forces at a site of damage in the cartilage may make the tissue more susceptible to continued long-term degeneration. Various biological treatments are currently available, but all have drawbacks. Alternatively, a contoured articular resurfacing implant is developed to offer a treatment to such full thickness chondral defects [1,3,4]. The main goal of using metal implants, to fill the degenerated portion of the cartilage, is to seal the surrounding cartilage so that further damage can be prevented, and to re-establish the integrity of the joint articulating surface. Many researchers have studied the safety, feasibility and reliability of the metal implants in animal models from a biological point of view [3,4]. They showed promising results. Till date, the mechanical behavior of cartilages surrounding the implant has not been studied, even in animal models. It is essential to understand the time dependent behavior of the cartilages due to biphasic nature of cartilage. Any protrusion of metal implant into the joint cavity damages the opposing soft tissue [1]. In order to avoid this, the positioning of implant together with the behavior of the cartilages immediately surrounding the implant have to be studied.
Collagen Network Topology is Influenced by Collagen Concentration, But Not by Co-Gelation With Fibrin
Authors: Lai Victor K. , Sander Edward A. , Lake Spencer P. , Tranquillo Robert T. , Barocas Victor H.
Published: July 2013

Extracellular matrix (ECM) proteins (e.g. collagen, elastin) play an important role in biological tissues. In addition to conferring mechanical strength to a tissue, the ECM provides a biochemical environment essential for modulation of cellular responses such as growth and migration. Collagens are the dominant protein of the ECM, with collagen type I being most abundant. Our group and others have shown that the mechanical properties of a collagen I matrix change with collagen concentration, and when formed in the presence of a secondary fibril network such as fibrin [1]. We are interested in collagen-fibrin systems because our group uses fibrin as the starting scaffold material for cardiovascular tissue engineering, which produces interpenetrating collagen-fibrin matrices during the remodeling process as the fibrin network is degraded and replaced with cell-deposited collagen [2]. Fibrin and collagen networks are also present together around the thrombus during the wound healing process. Research has shown that ECM mechanical properties are correlated with their overall network structure characteristics such as fibril diameter [3]. Currently we have a modeling framework that generates an ECM microstructural network which can be used to predict the overall properties of a bioengineered tissue [4]. This framework allows exploration of the structure-function relation, but how the structure depends on composition remains poorly understood, especially in multi-component gels. Thus, the objective of this work was to quantify the collagen network architecture in pure collagen gels of different concentrations and in collagen-fibrin co-gels.
The Mechanical Consequence of Removing the Superficial Zone of Articular Cartilage
Authors: Hosseini S. M. , Wu Y. , van Donkelaar C. C. , Ito K.
Published: July 2013

Articular cartilage (AC) functions as a load-bearing, low friction, and wear resistant material in diarthrodial joints. The distribution of AC matrix composition is highly depth-dependent. The fluid fraction in AC is 80% and decreases from surface to the depth of the tissue [1]. Collagen constitutes 70% of the tissue dry weight, and is highest in the superficial and deep zones and lowest in the middle zone [2]. Proteoglycans (PG’s) constitute 20–30% of the tissue dry weight. PG’s are lowest in the superficial zone, and highest in the middle zone. Although the PG content is lower in the deep zone than in the middle zone, the fixed charge density (FCD) is highest in the deep zone [3]. Apart from AC composition, its structure is also depth-dependent. In the superficial zone collagen fibers are densely packed, and are arranged parallel to the articular surface. In the middle zone collagen fibers are more randomly arranged. In the deep zone, the collagen fibers have their largest diameters and are arranged perpendicular to the subchondral bone (Fig. 1) [4].
Assessment of Aortic Graft Impact on Hemodynamics
Authors: Vardoulis Orestis , Coppens Eline , Martin Bryn , Reymond Philippe , Stergiopulos Nikos
Published: July 2013

In vivo studies have revealed that aortic grafts augment heart load and alter blood pressure and flow waveforms [1]. A one-dimensional model of the arterial tree was developed in order to analyze the different mechanisms by which proximal and distal aortic grafts affect hemodynamics. Graft compliance and properties were based on in vitro tests. Predicted pressures at the aortic root were compared for the control, proximal and distal graft case. Pulse pressure increased by 21% and 10% in presence of a proximal and distal graft, respectively. The distal graft resulted in a wave reflection coefficient of 0.62 while for the proximal graft the wave reflection coefficient was 0.46. The physiological mechanism behind the rise of pressure is dual and it is critically affected by the graft’s compliance and position. In case of a proximal graft, the primary reason for aortic pressure increase is the augmentation of aortic characteristic impedance, which augments the forward running pressure wave, while for the distal graft the wave reflections are major contributors to the total pressure wave. Overall, the proximal graft altered hemodynamics to a greater extent than a distal aortic graft.
Role of Collagen Content and Architecture in the Load Bearing Capabilities of Tissue-Engineered Cartilage
Authors: Khoshgoftar M. , van Donkelaar C. C. , Ito K.
Published: July 2013

A promising treatment for damaged cartilage is to replace it with tissue-engineered (TE) cartilage. However, the insufficient load-bearing capacity of today’s TE cartilage is an important limiting factor in its clinical application. In native cartilage, collagen fibers resist tension and proteoglycans (PG’s) attract water through osmotic pressure and resist its flow, which allows cartilage to withstand high compressive forces. One of the main challenges for tissue engineering of mechanically stable cartilage is therefore to find the cues to create an engineered tissue with an ultrastructure similar to that of native tissue. Currently, it is possible to tissue engineer cartilage with almost native PG content but collagen reaches only 1/4 of the native content [1]. Furthermore, the specific depth dependent arcade-like organization of collagen in native cartilage (i.e. vertical fibers in the deep zone and horizontal fibers in the superficial zone), which is optimized for distributing loads, has not been addressed in TE’d cartilage. However, the relative importance of matrix component content and collagen network architecture to the mechanical performance of TE cartilage is poorly understood, perhaps because this would require substantial effort on time consuming and labor-intensive experimental studies. The aim of this study is to explore if it is sufficient to produce a tissue with abundant proteoglycans and/or collagen, or whether reproducing the specific arcade-like collagen network in the implant is essential to develop sufficient load-bearing capacity, using a numerical approach.
Adaptive Bone Remodeling Theory Applied to Cervical Laminoplasty
Authors: Kode Swathi , Kallemeyn Nicole A. , Smucker Joseph D. , Fredericks Douglas C. , Grosland Nicole M.
Published: July 2013

Laminoplasty, considered an alternative to laminectomy, is intended to relieve pressure on the spinal cord while maintaining the stabilizing effects of the posterior elements of the vertebrae. Open-door laminoplasty (ODL) includes opening of the lamina from either the left or right side with the contralateral side acting as hinge. The main aim of laminoplasty is to recreate a stable laminar arch that preserves laminar opening. As hinge failure is a commonly encountered problem during laminoplasty, it is necessary to understand the process of bone remodeling post laminoplasty. This study aims at implementing a computer simulation method to predict bone remodeling in accordance with Wolff’s Law. Mathematical models are based on the principle that bone remodeling is induced by a local mechanical signal that activates regulating cells to adapt accordingly by changing either the internal or external morphology [5].
Use of the Photoelastic Method to Determine the Wall Stress in Realistic Abdominal Aortic Aneurysm Models
Authors: Doyle Barry J. , Callanan Anthony , Killion John , McGloughlin Timothy M.
Published: July 2013

Abdominal aortic aneurysms (AAAs) remain a significant cause of death in the Western world with over 15,000 deaths per year in the US linked to AAA rupture. Recent research [1] has questioned the use of maximum diameter as a definitive risk parameter as it is now believed that alternative factors may be important in rupture-prediction. Wall stress was shown to be a better predictor than diameter of rupture [1], with biomechanics-based rupture indices [2,3] and asymmetry also reported to have potential clinical applicability [4]. However, the majority of numerical methods used to form these alternative rupture parameters are without rigorous experimental validation, and therefore may not be as accurate as believed. Validated experiments are required in order to convince the clinical community of the worth of numerical tools such as finite element analysis (FEA) in AAA risk-prediction. Strain gauges have been used in the past to determine the strain on an AAA [5], however, the photoelastic method has also proved to be a useful tool in AAA biomechanics [6]. This paper examines the approach using three medium-sized patient-specific AAA cases at realistic pressure loadings.
Stiffness of the Transverse Carpal Ligament Under the Influence of Collagenase
Authors: Prantil Ryan K. , Mondello Tracy A. , Yu Suk H. , Pervaiz Khurram , Woo Savio L-Y. , Li Zong-Ming
Published: July 2013

Forming the palmar roof of the carpal tunnel, the transverse carpal ligament (TCL) continues to be the surgical target for carpal tunnel release which aims to relieve the symptoms of patients with carpal tunnel syndrome. However, the surgical procedures may cause several biomechanical and anatomical problems for the carpal tunnel [1]. Therefore, an alternative, aimed at preserving the TCL, might alleviate patients’ post-operative complications. Using a geometrical model, Li et al. showed that the cross-sectional area of the carpal tunnel can be effectively increased by TCL elongation [2]. Theoretically, stiffness reduction could facilitate a ligament’s capability to elongate. Past studies have shown that the utilization of the collagenase enzyme altered the mechanical properties of a soft tissue [3, 4]. It also has been used to treat Dupuytren’s Contracture [5] because collagenase breaks the peptide bonds within collagen fibers [6]. The usage of collagenase could effectively reduce the stiffness of the TCL allowing for the ligament to elongate and for the median nerve to decompress. Thus, the purpose of our study is to determine the effect of collagenase on the stiffness of the TCL. We hypothesize that the stiffness of the ligament will progressively decrease due to the enzymatic effect of collagenase.
Mechanical Testing of a New Prosthetic Anterior Cruciate Ligament Using Biocompatible Fibrous Hydrogel Constructs
Authors: Bach Jason S. , Detrez Fabrice , Baxter Frances R. , Cantournet Sabine , Cherkaoui Mohammed , Corté Laurent , Ku David N.
Published: July 2013

The anterior cruciate ligament (ACL) is an important intra-articular structure in the knee joint that prevents excessive anterior tibial translation and resists internal rotational loads. Its rupture is one of the most common injuries of the knee and about 100,000 ACL reconstructions are performed each year in the United States. The current techniques for reconstruction involve replacing the ACL with autografts, most commonly from the hamstrings or patellar tendons, though use of these grafts is associated with various drawbacks, the most prominent of which is donor site morbidity. Over the past 30 years, numerous prosthetic devices for ACL replacement have been made with a wide range of materials. However none of them have demonstrated positive long term results in vivo, and no such devices are currently approved by the FDA for clinical use. Failures of previous devices mostly originate from a lack of biocompatibility due to immunogenic particulation or from mechanical failures causing prosthetic laxity and knee instability as the result of creep or rupture by wear and fatigue.
Temporomandibular Joint Kinematics of the Rabbit Model With Mechanically Disrupted Occlusion
Authors: Henderson Sarah E. , Almarza Alejandro J. , Tashman Scott , McCarty Amy L.
Published: July 2013

Degeneration of the articulating surfaces and pain associated with temporomandibular joint (TMJ) dysfunction are the primary symptoms of TMJ disorders (TMDs), where normal life activities such as eating, talking, and even sleeping may be drastically impaired [1–3]. To accelerate the discovery of effective therapeutic interventions for the treatment of TMD pain, we have been establishing a novel non-invasive approach for objectively assessing the presence of joint hypersensitivity. Our approach to identify chronic joint pain is based on evidence that all of the etiological factors associated with TMD pain implicate remodeling and degeneration of the joint in response to alterations in motion and loading. The injury model used for this study was a reversible, mechanical model through splint placement on the molars. It is hypothesized that arthrokinematic analysis will identify a specific pattern of functional changes that constitute a signature for the presence of irreversible damage.
Estimation of Left Ventricular Wall Stiffness by Analysis of Late Diastolic Pressure Components
Authors: Niebel Casandra L. , Stewart Kelley C. , Ohara Takahiro , Charonko John J. , Vlachos Pavlos P. , Little William C.
Published: July 2013

Left ventricular diastolic dysfunction (LVDD) is any abnormality in the filling of the left ventricle and is conventionally evaluated by analysis of the relaxation driven phase, or early diastole. LVDD has been shown to be a precursor to heart failure and the diagnosis and treatment for diastolic failure is less understood than for systolic failure. Diastole consists of two filling waves, early and late and is primarily dependent on ventricular relaxation and wall stiffness.
Modified Challenge-Based Teaching of Biotransport Phenomena
Authors: Han Bumsoo
Published: July 2013

Major challenges of teaching biotransport phenomena are the interdisciplinary nature of biotransport principles, and diverse backgrounds of students from biology, biomedical engineering, mechanical engineering and chemical engineering majors. These challenges make traditional lecture-based instruction less effective, and difficult to implement new discovery and knowledge into the lecture material. In order to overcome these challenges, it has been proposed to teach biotransport phenomena based on the “How People Learn” (HPL) methodology [1–3]. The HPL methodology is a challenge-based pedagogic method in which students learn the principles through solving the assigned challenges. Adaptation of this pedagogic method to bioengineering courses is actively being developed and supported by NSF (VaNTH-ERC). This method has been shown to be very effective in teaching interdisciplinary science and engineering principles if the challenge modules are carefully designed.
Development of a Powered-Knee Transfemoral Prosthesis Prototype
Authors: Hoover Carl D. , Fite Kevin B.
Published: July 2013

Commercial prosthetic limb development for transfemoral amputees has historically focused on legged locomotive function with energetically dissipative or conservative limbs. While such passive devices are effective at approximating the mechanics of the knee during level walking and stair/slope descent, the inability of these limbs to impose net positive power prevents amputees from executing a number of activities of daily living. Activities such as ascending slopes, ascending stairs, and jumping require net positive power outputs that are not fully realizable with current prosthetic leg technology [1–3]. While functionality has improved with microprocessor-based passive limbs [4], amputees continue to exhibit increased metabolic demands and non-anthropomorphic asymmetric gait [5].
Histology-Based, Lesion-Specific Modeling of Stress Differences Between Plaque Rupture and Plaque Erosion
Authors: Campbell Ian C. , Virmani Renu , Oshinski John N. , Taylor W. Robert
Published: July 2013

Plaque erosion is a cause of thrombosis wherein a thrombus forms over an atherosclerotic plaque without any disruption of the fibrous cap. This is in contrast to plaque rupture, traditionally considered the main cause of atherosclerosis-related thrombosis and frequently studied in biomechanics, wherein the fibrous cap becomes disrupted and exposes the lipid core of the plaque to the blood pool. Also unlike plaque rupture, plaque erosion has been observed to happen most frequently in women [1]. Despite identification, the cause of plaque erosion remains unknown and has been virtually unstudied from a biomechanical perspective. In this study, we employ a unique high-resolution, histology-based finite element model of solid wall stresses to investigate biomechanical differences between plaque rupture and plaque erosion. In future studies, this computed stress distribution can be correlated to expression of biomarkers related to the plaque disruption process in order to investigate the cause of plaque erosion.
Discovery of Side- and Shear-Dependent miRNAs and mRNAs in Human Aortic Valvular Endothelial Cells
Authors: Holliday Casey J. , Ankeny Randall F. , Jo Hanjoong , Nerem Robert M.
Published: July 2013

Aortic valve (AV) disease is diagnosed by severe symptoms, such as calcification, and typically treated by AV replacement and repair surgeries. The mechanism by which AV disease occurs, specifically the role of the endothelium remains relatively unknown. It is known that disease preferentially occurs on the fibrosa, or aortic side, where it is exposed to disturbed, oscillatory flow, whereas the ventricularis, or side facing the left ventricle, experiences pulsatile, laminar shear and remains non-calcified [1, 2]. Research shows that regulation of miRNAs, short nucleotide segments targeting mRNAs, coincides with cardiovascular pathologies [3] though expression profiles of miRNAs and the mRNAs they modulate in human AV endothelial cells (HAVECs) have not been reported. We hypothesize that disturbed flow conditions present on the fibrosa stimulate ECs to modify expression of genes and miRNAs to induce a pro-inflammatory phenotype.
Effect of Surface Charge on Gold Nanoparticle Biotransport: An In Vivo Blood and Biodistribution Study
Authors: Shah Neha B. , Bischof John C.
Published: July 2013

Intravenously injected nanoparticles (NPs) hold great promise for clinical diagnostic and therapeutic applications. While several NPs for such clinical applications have emerged in various designs (metallic, polymeric, quantum dots etc.) [1], a critical issue in their in vivo use is the lack of fundamental studies examining the effects of physicochemical parameters (shape, size, surface properties etc.) on blood circulation, kinetics of accumulation and elimination as well as toxicity [2–4]. We hypothesize that blood, the first medium of interaction in the body, is a major determinant of biotransport and biodistribution. Recent and past in vitro studies have shown that NPs interact with serum proteins (including complement factors), cause platelet aggregation and red blood cell hemolysis, and are taken up by phagocytic cells. However, to our knowledge a detailed in vivo study of the interaction of metallic nanoparticles with blood components as a function of their surface properties does not yet exist.
Investigation of Damage in Medial Collateral Ligaments
Authors: Guo Zheying , De Vita Raffaella , Davis Frances M. , Barrett Jennifer G.
Published: July 2013

Understanding how tissue damage leading to sprains initiates and propagates is essential for developing adequate prevention and treatment strategies. Recent studies [1] have focused on characterizing the cellular and micro-structual origin of damage in rat medial collateral ligaments (MCLs). Provenzano et al. [1] demonstrated that structural damage occurs at 5.14% strain. In their study, damage was defined as the non-recoverable increase in strain after different stretches were applied to the MCLs.
Distribution of Nanomechanical Properties and Mineralization of the Osteochondral Interface in the Femoral Head
Authors: Pak Rebecca , Campbell Sara E. , Paietta Rachel C. , Ferguson Virginia L.
Published: July 2013

Stiff vertebral bone and compliant hyaline articular cartilage (HAC) anchor together through a thin (∼100’s of microns) region of articular calcified cartilage (ACC). This bone–cartilage, or osteochondral (OC), interface may play a role in osteoarthritis pathogenesis through increased mineralization, disrupting loading, and damaging neighboring tissues [1,2]. Load transmission through OC regions is poorly understood, thus limiting understanding of disease progression and ability to engineer OC interface-like tissues [3].
Theoretical Study of Cellular Uptake of QD Nanoparticles
Authors: Guan Yingxue , Zhang Aili , Xu Lisa X.
Published: July 2013

Cellular uptake kinetics of nanoparticles is one of the key issues determining the design and application of the particles. It is widely accepted that the nanoparticles getting into the cells mainly by endocytosis[1], a process which is found to be inhibited distinctly when temperature is below 4 °C. In fact, some nanoparticles could enter cells at lower temperatures or when the endocytosis was blocked[2–4]. Models describing the intrusion of the nanoparticles into cells only take the endocytosis process into consideration5. Meanwhile, other than the factors as concentration, size, electrical charge, temperature is also an important parameter affecting the uptake process, as binding with the receptors on the cell membranes[6] and endocytosis of nanoparticles[2, 3, 7] and etc. are all energy related. Thus, in this paper, the influence of temperature on the cellular uptake of QDs is studied experimentally, and a two-step mass transfer model describing the cellular internalization of the nanoparticles is developed by taking the temperature effect into consideration.
Towards a Full-Scale Model of Carotid Artery Stenting: Virtual Stent Implantation and Its Hemodynamic Impact
Authors: De Santis Gianluca , Trachet B. , Conti M. , De Beule M. , Segers P. , Auricchio F. , Verdonck P. , Verhegghe B.
Published: July 2013

Carotid Artery Stenting (CAS) has emerged as a safe and cost-effective endovascular treatment for patients at high risk for endarterectomy, even though its efficacy remains a matter of debate. The success rate of CAS depends, among other factors, on the selection of the appropriate device. Most research focused on the performance of carotid stents per se (e.g. radial stiffness, flexibility), the stent-vessel interaction from a structural perspective (e.g. vessel stress, lumen gain), or the effect of the stent on the vessel flow from a fluid dynamic perspective. Nonetheless, investigating the stented-vessel hemodynamics requires both a structural analysis, to obtain the post-implantation domain, and a fluid dynamic analysis. In this paper, we provide a full-scale computational approach to predict stenting effectiveness in restoring the flow given a prosthesis and a patient-specific vessel. As a first step, a stent is virtually implanted in a mildly-stenosed artery using the Finite Element Method (FEM); then, the stented lumen is virtually perfused reproducing realistic blood-flow conditions using Computational Fluid Dynamics (CFD).
Mechanical Mechanism of Circadian Fluctuations Regulated Haematopoietic Stems Cell Release
Authors: Yan W. W. , Liu Y. , Fu B. M.
Published: July 2013

Haematopoietic stem cells (HSCs) circulate in the bloodstream under flow conditions, but the mechanical mechanisms of governing their physiological trafficking in mammals are still not yet clearly understood. The mobilization of HSCs and their progenitors into the circulation represents the basis for modern bone marrow transplantation procedures [1]. Recently, Mendez-Ferrer et al. performed experimental investigations on mice [2]. They demonstrated that the circulating HSCs and their progenitors exhibit robust circadian oscillations, and the circadian fluctuations could also be significantly altered when the HSCs were subjected to different time of lighting. These results indicated that the photic cues could affect the trafficking of HSCs in healthy animals. This implies that the light is the stimulus of HSCs release. When the HSCs are exposed to light, the HSCs release would markedly increase; when the HSCs are in darkness, the HSCs release keeps low efficiency. In this study, we numerically simulate this phenomenon to study the mechanical mechanism of circadian fluctuations regulated HSCs release under the influence of periodic lighting time.
Biocorrosion and Biomechanical Analysis of Vascular Stents
Authors: Kapnisis Konstantinos , Halwani Dina , Brott Brigitta , Lemons Jack , Anderson Peter , Anayiotos Andreas
Published: July 2013

Despite advances in endovascular stent design, stent structural integrity and in-stent restenosis remains a significant clinical problem worldwide. The role of stent corrosion and metallic ion release has not been thoroughly studied and little attention has been given to the interaction of stent materials with the surrounding vessel wall and the mechanical forces involved after implantation. Our recent studies on Stainless Steel (SS), Cobalt-Chromium (CoCr) and Nickel-Titanium (NiTi) stents obtained from a tissue retrieval resource from cadavers with accompanying clinical histories, have revealed that these stents undergo corrosion in vivo, with significant release of metallic ions into surrounding tissues [1]. It is believed that high concentrations of metal ions from stents are toxic to vascular smooth muscle cells [2] and stimulate both inflammatory and fibrotic reactions leading to neointimal formation and a predisposition to device failure [3]. When this is combined with altered biomechanics of flow and motion, it creates a favourable environment for the development of restenosis. To separate the mechanical effects from the local environmental effects on the stent surface, we performed in-vitro mechanical studies on various combinations of stents under low and high curvature and in overlapping positions to compare the results of fretting, pitting and gouging with the explanted stents.
Teaching Experience in Biotransport Course for Undergraduates of Biomedical Engineering
Authors: Xu Lisa X. , Zhang Aili
Published: July 2013

For undergraduate student in biomedical engineering, they usually have very limited background of thermodynamics, heat mass transfer. Fundamental concepts of heat and mass transfer, thermodynamics are necessary at the beginning of the course. For this purpose, we found that Prof. John Chato’s book “Fundamentals of Bioheat Transfer” provides good text and it has been used successfully through our teaching. For example, after introducing the energy conservation law, a focused discussion on how the law is used in biological systems (how energy is generated from bio-chemical reactions, et.al) can be launched. Thermal resistance method and radiation network are easily accepted by the BME students as they have strong electrical background. Vasculature is one of the most important factors in bioheat transfer. It is also important in biomedical engineering field. Thus, the anatomic structure, quantification, thermal equilibrium length of blood vessels, are all taught in details. The Pennes equation and its applications are certainly necessary topics and taught right after the temperature measurement technique session. Medical applications, including hyperthermia, thermal ablation, cryosurgery, cryopreservation, burn evaluation etc. are given from both experimental and theoretical points of view. At the end, successful commercial products and models are also introduced.
Hemodynamic Performance of Oversized Flow Diverters
Authors: Mut Fernando , Cebral Juan R.
Published: July 2013

Although endosaccular coiling of aneurysms has been shown to be effective and has arguably replaced surgery for the treatment of most aneurysms it has significant limitations in achieving durable occlusion of many large and giant aneurysms because of a propensity for recanalization. For this reason flow diverting stents are increasingly been considered as a therapeutic alternative to surgical clipping and endovascular coiling. The aim of flow diverting stents is to create a stable hemodynamic environment within the aneurysm favorable for thrombosis and aneurysm occlusion, while maintaining the patency of any side branch that may be crossed by the device. The hemodynamic performance of these devices and the outcome of the procedures depend on their porosity and geometric characteristics [1]. However, the local porosity and stent cell geometry after implantation into a given artery depends on the choice of the stent diameter. Typically, stents are oversized to achieve a good wall apposition. Thus, the goal of this study was to investigate the effect of stent oversizing on its hemodynamic performance.
Contrast-Free Blood Flow Velocity Profile Measurement With Ultrasound in Real-Time
Authors: Koutsouridis G. G. , Bijnens N. , van Geldermalsen S. , Brands P. J. , van de Vosse F. N. , Rutten M. C. M.
Published: July 2013

In clinical practice, ultrasound is frequently used as a non-invasive method to estimate geometric properties of large arteries such as diameter and intima-media wall thickness and in a separate Doppler measurement hemodynamic variables such as blood velocity. For the purpose of deducing biomechanical parameters and hemodynamic variables that are related to the development of Cardiovascular Disease, such as compliance and vascular impedance, the assessment of only geometry and blood velocity is not sufficient. A simultaneous and non-invasive assessment of blood flow and blood pressure is required. This can only be obtained by an accurate and simultaneous measurement of the blood velocity distribution and wall motion, which is not feasible with the commonly used Doppler technique.
Experimental and Theoretical Evaluation of Failure Properties for Immature Tissue Engineered Cartilage
Authors: O’Connell Grace D. , Hung Clark T. , Ateshian Gerard A.
Published: July 2013

Articular cartilage functions as a low friction load bearing soft tissue. The contact area and load distribution is highly location dependent in the knee joint [1]. Regeneration and repair strategies for osteoarthritis include tissue-engineered cartilage, which will need to bear high mechanical stresses and strains. There has been variable success in developing tissue-engineered cartilage with compressive mechanical properties comparable to native tissue (modulus = 40kPa – 1000kPa) [2–4]. There has also been some debate on the costs and benefits of implanting immature constructs and allowing them to elaborate their properties in situ, or culturing them in vitro and implanting them only after they have elaborated sufficiently functional properties. The former strategy may benefit from using the body as a bioreactor and might promote better construct integration, though constructs may bee to frail to sustain the physiological loading environment. The failure properties of engineered cartilage have not been widely evaluated, and may greatly affect the successful implantation of engineered cartilage as a repair strategy for the knee joint. The objective of this study was twofold: 1) to evaluate the failure properties of agarose hydrogels used as scaffolds in our tissue engineering studies, and 2) to evaluate whether joint congruence might sufficiently shield immature constructs to prevent their early failure. The long-term hypothesis of this study is that engineering analyses, based on an informed failure criterion for tissue constructs, might allow proper pre-assessment of failure risk for a given set of construct properties, dimensions, and joint congruence.
Reflections on Quantitative Gamma Imaging of Cell-Surface Interactions
Authors: Eberhart Robert C.
Published: July 2013

Molecular and cellular interactions with foreign surfaces can be noninvasively measured by isotope imaging techniques. Long available for probing cell behavior, these techniques are now employed in molecular studies of disease progression, such as Alzheimer’s [1]. This paper reviews results obtained by noninvasive dual label gamma scintigraphy for the transient adhesion of platelets and neutrophils to pump-oxygenators during cardiopulmonary bypass (CPB). In this application, characteristic cell-foreign surface adhesion and release patterns are observed during CPB in the pig, as a function of oxygenator design and surface chemistry. Cell distributions in internal organs post-CPB are also affected by these processes. This method can be adapted to other settings where the understanding of protein-cell interactions with native and foreign surfaces is at issue, including fibrinogen-cell interactions, bacterial colonization, etc.
Correlation of Local Mechanical Environment to Mechanically Induced Tissue Phenotype During Altered Bone Fracture Healing
Authors: Miller G. J. , Patel P. G. , Morgan E. F.
Published: July 2013

Numerous studies have demonstrated that mechanical factors affect the healing process of skeletal tissues and can either enhance or hinder repair of orthopaedic injuries. Several mechanobiological theories have been proposed that relate specific mechanical stimuli to patterns of skeletal tissue differentiation1,2,3. However, rigorous tests of these theories have been difficult to carry out because few experimental data are available on local stress and strain magnitudes induced by mechanical stimulation of skeletal tissues in vivo.
Basement Membrane Collagen Glycation Prevents Endothelial Cell Response to Strain due to Altered Focal Adhesion Formation
Authors: Figueroa Dannielle Solomon , Clyne Alisa Morss
Published: July 2013

Vascular morbidity and mortality are primary complications of diabetes and have been correlated with unregulated blood glucose control. Endothelial cells that line the vasculature are known to be dysfunctional in hyperglycemia (1). Furthermore, the high glucose environment promotes basement membrane protein glycation and enhanced cross-linking. This can increase matrix stiffness, decrease matrix degradation, and potentially alter the spatial distribution of cell-matrix binding sites.