bluuebunny/crossref_metadata_2025 huggingface dataset:
Visualization and Quantification of Gold Nanorods Distribution in Prostatic Tumors Using MicroCT Imaging
Authors: Manuchehrabadi N. , Attaluri A. , Cai H. , Edziah R. , Lalanne E. , Bieberich C. , Ma R. , Johnson A. M. , Zhu L.
Published: July 2013

One uncertainty in use of gold nanorods for laser photothermal therapy is the non-uniform spreading of gold nanorods in tissue after either systemic delivery or intratumoral injections. High concentration of gold nanorods in certain areas influences the resulted optical absorption of the laser and thermal damage to tumors. This also provides challenges in designing optimal heating protocols via modeling thermal transport in laser photothermal therapy. For successful cancer treatment, the tissue should be heated with minimum thermal dosage to induce tumor cell damage, while minimizing overheating in the surrounding healthy tissues. Thus, one of the main challenges for reliable cancer therapy is to precisely control loading and distribution of gold nanorods in the tumour tissue. The critical mass transport processes are the distribution of gold nanorods after injection to the tumor and the redistribution of gold nanorods during laser treatment. Since tumors are opaque, nanostructure distribution in tissue is often studied either by theoretical modeling approaches1, or via dye enhanced imaging on superficial layers of tumors.2 It is important to find a technique which can directly visualize and analyze three-dimensional nanostructure distribution of tumors. Three-dimensional reconstructions of tumors with the ability to trace gold nanorod spreading have the potential for precise theoretical simulation of temperature fields. Previous studies showed that computer tomography (CT) scan is a promising technique to be utilized to characterize the distribution of intratumorally injected magnetic nanoparticles in tumors 3.
Facet Translation Analysis in the Lumbar Spine: An Application in Posterior Dynamic Stabilization
Authors: Cook Daniel J. , Yeager Matthew S. , Cheng Boyle C.
Published: July 2013

Facet articulation in the human lumbar spine has not been thoroughly characterized with regard to the effects of degeneration or surgical intervention. Kozanek et al. investigated the translation and rotation of the facets in 11 healthy adult subjects during maximal voluntary bending [1]. Li et al. used the same measurement technique on a cohort of 10 patients with degenerative disc disease (DDD) and found some significant differences in facet motion compared to a cohort of healthy patients [2]. Jegapragasan et al. investigated facet translations in intact lumbar spines in vitro and found the technique of facet translation analysis (FTA) to yield significantly different results compared to a similar analysis based on a vertebral body based coordinate system [3]. This abstract describes the application of this FTA technique in evaluating a posterior dynamic stabilization (PDS) system.
Finite Element Based Injury Metrics for Pulmonary Contusion From Vehicle to Vehicle Crash Simulations
Authors: Danelson Kerry A. , Stitzel Joel D.
Published: July 2013

Motor Vehicle Crashes (MVCs) are a public health problem in the United States. In 2009, 33,808 Americans were killed in a MVC and 2.22 million more were injured.4 Pulmonary contusion (PC) is a common injury following MVC with over 38% of the Abbreviated Injury Scale (AIS) 3+ thoracic injuries identified as some form of PC in a recent National Automotive Sampling System (NASS) study.5 Miller et al. correlated the percent injured lung to the possibility of developing Acute Respiratory Distress Syndrome (ARDS). The results indicated that if 20% of the lung was injured, the incidence of ARDS sharply increased with seventy-eight percent of those patients developing ARDS.2 The significance of these findings is that the volumetric measurement of PC can predict possible clinical outcomes.
Analyzing the Hysteresis of the Lumbar Spine
Authors: Hanlon Andrew D. , Cook Daniel J. , Yeager Matthew S. , Cheng Boyle C.
Published: July 2013

Significant advances have been made in the field of spine biomechanics with the introduction of continuous testing machines and new testing protocols. [1] Despite all the technological achievements, range of motion (RoM) continues to be the only widely agreed upon, standardized metric for data analysis. In load-controlled flexibility testing, displacement is typically recorded over three loading cycles between established limits in specific modes of loading. The first two cycles are intended for preconditioning, and the data from the third cycle is used for analysis. [2] Plotting displacement versus load defines the hysteresis inherent to the motion segment.
Robotically Controlled Variation of the Instantaneous Center of Rotation: The Effects on Kinetics and Kinematics of Cervical Spine
Authors: Colbrunn R. W. , Bonner T. F. , Mageswaren P. , Bartsch A. , McLain R. F.
Published: July 2013

Cervical spine loads are complex, with different head and neck movements producing different spine loading conditions. Imagine performing a chin tuck, (this simple action predominantly utilizes mostly upper cervical segments), or stretching out your neck to look down over something (this action requires the utilization of lower level cervical segments). The effect in both cases is neck flexion, but cervical spine loads may vary greatly. With a trend towards increasing fidelity and in vivo applicability of in vitro simulations [1], this study aimed to provide a novel biomechanical assessment of the influence of varying the location of the regional Instantaneous Center of Rotation (ICR) on the kinetics and kinematics of the cervical spine.
CFD Challenge: Giant Internal Carotid Artery Aneurysm Simulation Using the Commercial Finite Volume Solver Fluent
Authors: Cito S. , Pallarés J. , Vernet A. , Cuesta I.
Published: July 2013

The main objective of ECoMMFiT is to advance in the knowledge of the structure of flows and their effect on the heat and mass transfer processes in problems with fundamental, clinical, industrial and environmental interest using experimental, computational and analytical tools. For this Challenge, CFD simulations were performed using the commercial finite-volume solver FLUENT 12 (ANSYS).
CT-Based Muscle Attenuation May be Able to Account for Age- and Muscle-Specific Differences in Maximum Muscle Stress
Authors: Anderson Dennis E. , Bruno Alexander G. , Allaire Brett T. , Bouxsein Mary L.
Published: July 2013

In musculoskeletal modeling, isometric muscle strength has been primarily determined based on muscle size. Specifically, the maximum force a muscle can produce may be calculated as: (1)FMAX=MMS×PCSA where FMAX is maximum isometric muscle force, MMS is maximum muscle stress, and PCSA is muscle physiological cross-sectional area. In general, modeling studies have selected a constant value of MMS, and applied it to all muscles in the model. However, the values reported in the literature for MMS vary widely [1, 2], from as little as 23 N/cm2 up to 137 N/cm2. Furthermore, MMS is likely lower in older adults than young adults, as age-related declines in muscle strength are significantly greater than declines in muscle mass [3], and the specific tension of gastrocnemius fascicles is 30% lower in elderly men than young men [4]. In addition, MMS is not constant between muscle groups. For example, the MMS of the elbow flexors is much greater than that of the elbow extensors [1], while the MMS of the ankle dorsiflexors is more than twice that of the ankle plantar flexors [5]. Thus, the use of a single constant for MMS in musculoskeletal models does not account for differences between individuals or muscle groups, and there is a need for a quantitative approach to assign different values of MMS to muscles in musculoskeletal models.
Adaptive Hybrid Control Algorithm With Iterative Learning for Robotic In Vitro Biomechanical Testing of Spine
Authors: Bonner T. F. , Gilbertson L. , Colbrunn R. W.
Published: July 2013

In spine testing, methods have been developed to apply pure moments to a single axis of the spine to elucidate the mechanical properties of the spine. The application of those concepts continues to be applied with custom loading frames, custom robotics systems, and adaptation of commercial robotic technology. With these systems and pure moment testing, spinal biomechanics variables such as the neutral zone and range of motion can be determined. As more complex testing systems with higher degrees of freedom (DOF) capabilities are developed, dynamic testing becomes a possibility. However, these more complex testing systems require more complex control schemes.
Characterization of Human Cortical and Trabecular Bone Structural Change by NMR and Micro-CT
Authors: Ni Qingwen , Bredbenner Todd
Published: July 2013

The techniques of low-field pulsed proton nuclear magnetic resonance (NMR) spin relaxation and Micro-CT are described for assessment of structural changes of human cortical and trabecular bone in vitro. The technique involves spin-spin relaxation measurement and inversion spin-spin spectral analysis methods for NMR. From NMR measurement, the CPMG T2 relaxation data can be inverted to T2 relaxation distribution and this distribution then can be transformed to a pore size distribution with the longer relaxation times corresponding to larger pores. In Micro-CT measurement, each trabecular bone specimen was individually scanned using a micro-computed tomography (micro-CT) system and 12 micron dimensionally-isotropic voxels were reconstructed. Due to the resolution limitation, Micro-CT measurement on cortical bone was not success, however, NMR measurement was success for both cortical and trabecular bones.
Cell Morphology and Migration of Nucleus Pulposus Cells Depends on Substrate Stiffness and Ligand
Authors: Hwang Priscilla Y. , Gilchrist Christopher L. , Francisco Aubrey T. , Chen Jun , Setton Lori A.
Published: July 2013

Changes in nucleus pulposus (NP) cell phenotype and morphology are implicated in the progression of intervertebral disc (IVD) disorders. Understanding how changes in the NP cell microenvironment influence cell behavior and function is important for revealing how pathology-related changes in IVD extracellular matrix may affect NP cell biology. In this study, live-cell imaging techniques were utilized to study changes in cell migration and morphology when cultured upon substrates of different matrix proteins and stiffnesses. Results indicate that soft substrates containing matrix proteins promote cell clustering and cell-cell interactions which mimic in vivo conditions of healthy NP cells.
SBC2012 CFD Challange: Computational Hemodynamics of Intracranial Aneurysm Using the Finite Volume Solver Ansys Fluent
Authors: Kheyfets Vitaly O. , Finol Ender A.
Published: July 2013

The Vascular Biomechanics and Biofluids Laboratory is located in the Department of Biomedical Engineering at the University of Texas at San Antonio. The laboratory operates under the direction of Prof. Ender A. Finol, who has been working in computational hemodynamics for nearly a decade. For this challenge, the CFD simulations were performed by post-doctoral fellow Vitaly O. Kheyfets using the CFD solver Ansys Fluent v13 (Canonsburg, PA).
Ultrasound Hyperthermia: Dose Estimation and Device Design for Intraluminal and External Delivery
Authors: Gordon Danica , Thamire Chandrasekhar
Published: July 2013

Thermal ablation in the context of this study refers to destroying cancer cells by heating them to supraphysiological temperatures for appropriate times. Once the tumor cells and a small layer of surrounding tissue cells are killed, they are absorbed by the body over time. Compared to open surgery, radiation, and chemotherapy, thermal therapy can be less expensive and pose less risk of harmful post-procedural complications, while possessing the potential to be effective [1]. Currently microwave and radiofrequency ablation are in use for local hyperthermia; however, they lack the ability to focus heat into the target zones effectively or treat larger tumors without affecting the surrounding healthy tissue. In the current study, high frequency ultrasound (US) ablation is examined as a treatment modality because of its ability to focus and control heat effectively. Objectives of this study are to 1) develop thermal-damage correlations for US thermal therapy and 2) design delivery devices and associated treatment planning protocols. To achieve these goals, thermal damage information is first evaluated for a variety of cells and tissues from published data or pilot experiments. Required US dose levels are determined next through numerical experiments, followed by device design and estimation of thermal coagulation contours by comparing the temperature-history data against the thermal-damage data. Based on the analysis of the results for a range of parameters, namely, the applicator power, geometry, frequency, coolant parameters, treatment time, and tissue perfusion, treatment protocols are developed. Intraluminal, external, and interstitial modes of delivery are considered for focal sites in a variety of target areas. In the following sections, methods followed and sample results obtained are presented.
A Poroelastic Model of Skeletal Muscle Tissue Used to Predict Intramuscular Pressure
Authors: Morrow Duane A. , Haut Donahue Tammy L. , Odegard Gregory M. , Kaufman Kenton R.
Published: July 2013

Many single-phase, solid mechanics computational models of skeletal muscle have been created based on the assumptions that skeletal muscle is hyperelastic, transversely isotropic,1,2 and isovolumic. However, muscle has also been observed to have non-linear time-dependent behaviors that can be modeled using viscoelasticity or poroelasticity. The inherent viscoelasticity of muscle may not fully explain the time-dependent nature that may arise from extracellular fluid filtration3 and redistribution4 within the tissue. Further, intramuscular pressure (IMP) has been shown to have a heterogeneous distribution in muscle. This may be attributable to the movement of extracellular fluid, but the mechanisms of fluid redistribution are not completely understood. While a viscoelastic model may predict time-dependent responses of skeletal muscle, viscoelastic theory does not explain underlying causative tissue behaviors.5
Effect of Asymmetric Branching on Respiratory Flow and Pressure Losses: Implications for Asthma
Authors: Clark Alicia , Rossmann Jenn Stroud , Katz Ira M. , Martin Andrew R. , Caillibotte Georges
Published: July 2013

The distribution of inhaled air throughout human lungs is determined by the pressure losses in lung airways. These losses are reflections of patient health; alterations in measured pressure drops can indicate the presence of respiratory disease [1]. Pressure losses also have implications for the effective treatment of such diseases, as they affect how effectively inhaled medication can be distributed throughout the lung.
Tissue Engineering of the Intervertebral Disc
Authors: Wiltsey Craig , Christiani Thomas , Williams Jesse , Coulter Jamie , Demiduke Dana , Toomer Katelynn , English Sherri , Hess Bianca , Branda Amanda , Sheehan Joseph , Kadlowec Jennifer , Tulenko Thomas , Iftode Cristina , Vernengo Jennifer
Published: July 2013

Tissue engineering is a rapidly growing field of research that aims to repair damaged tissues within the body. Among tissue engineering approaches is the use of scaffolds to help regenerate lost tissues. Scaffolds provide structural support for specific areas within the body, namely load bearing regions, and allow for cells to be seeded within the scaffold for tissue regeneration. Scaffolds that specifically replicate the properties and/or composition of native tissues are referred to as biomimetic scaffolds.
Model Simulations Reveal VCAM-1 Augment PAK Activation Rates to Amplify p38 MAPK and VE-Cadherin Phosphorylation
Authors: Weidert Eric , Khanna Payal , Vital-Lopez Francisco , Dong Cheng
Published: July 2013

Metastasis is a complex process mediated by both adhesion molecules and chemokine secretion [1]. One important event during cancer metastasis is tumor cell extravasation through the endothelium [1]. In melanoma cancer, tumor cell extravasation is mediated by very late antigen (VLA)-4 molecule adhesion to vascular cell adhesion molecules (VCAM)-1 on endothelial cells [2]. High expression levels of VLA-4 integrin are associated with a marked increase in melanoma extravasation through endothelial layers [2]. The binding of VLA-4 to VCAM -1 induces the activation of downstream mitogen activated protein kinase (MAPK) signaling cascades, which regulate the vascular endothelial (VE)-cadherin junctions that hold together endothelial cells [2].
A Comparison of Hexahedral and Tetrahedral Finite Elements for Biphasic Analysis of Cartilage Micromechanics
Authors: Sibole Scott , Bennetts Craig , Erdemir Ahmet
Published: July 2013

Articular cartilage is a hydrated composite structure comprised of collagen type II extracellular matrix (ECM), collagen type VI pericellular matrix (PCM), and chondrocytes, each with low hydraulic permeability resulting in long viscoelastic stress relaxation times. Therefore, when subjected to fast loading, cartilage behaves as a nearly incompressible material [1]. When finite element analysis (FEA) is employed to solve mechanical problems involving nearly incompressible materials, a hexahedral finite element mesh is desirable [2]. Unfortunately, hexahedral mesh generation is difficult for complex geometries and often requires painstaking user-assisted construction which is often not feasible. Realistic chondron shapes and distributions within cartilage exhibit this complexity [3]. In these scenarios, a tetrahedral finite element discretization may need to be employed (Figure 1).
Patient Specific Modeling of Stage II Flatfoot Deformity Before and After Surgical Correction
Authors: Spratley E. Meade , Matheis Erika A. , Hayes Curtis W. , Adelaar Robert S. , Wayne Jennifer S.
Published: July 2013

Adult Acquired Flatfoot Deformity (AAFD) is a degenerative disease characterized by chronic changes in the joint alignment of the bones of the foot leading to significant pain and dysfunction. The early stages of the disease are thought to involve primarily the mechanical degradation of the soft-tissue support structures of the foot, namely the spring ligament, talocalcaneal interosseous ligaments, fibers of the anterior deltoid, and the long and short plantar ligaments, as well as a functional loss in posterior tibialis tendon (PTT) strength. [1] These changes manifest clinically as midfoot collapse, forefoot abduction, and valgus tilting hindfoot. [1–3] Various surgical corrections exist for Stage II AAFD to restore more normal biomechanical function to the foot. Treatment selection is most often based on clinical outcomes and surgeon preference. However, the optimal procedure(s) for an individual patient is unknown. Computer Aided Design (CAD) approaches offer advantages for evaluating foot function as well as the ability to predict pre-operatively the outcome of corrective procedures. This study developed a 3D patient specific computer model of the lower leg from a diagnosed Stage II flatfoot patient and evaluated its ability to predict foot function pre- and post-operatively through agreement with clinically relevant radiographic joint angles.
Effects of Electrical Stimulation on Select Functions of Bone Cells
Authors: Wechsler Marissa E. , Creecy Courtney M. , O’Neill Christine F. , Bizios Rena
Published: July 2013

The present in vitro study was motivated by scientific literature reports that show enhanced healing of bone fractures in experimental animals in response to electrical stimulation. The underlying cellular- and molecular level mechanisms responsible for new bone formation, however, were not studied at that time. Since then, advances in cell biology, biochemistry and biomedical engineering provided knowledge, models, and instrumentation to investigate these unanswered questions.
The Effect of Arthroscopic Partial Medial Meniscectomy on Tibiofemoral Stability
Authors: Bell C. P. , Arno S. , Hadley S. , Campbell K. , Hall M. , Beltran L. , Recht M. P. , Sherman O. H. , Walker P. S.
Published: July 2013

Irreparable tears of the posterior horn of the medial meniscus are the most common meniscal injury and arthroscopic partial meniscectomy is the current standard of care (1–3). However, despite the excellent results of partial meniscectomy, there is still little known regarding the effects of the size of a resection on tibiofemoral stability, as measured by laxity and anterior-posterior (AP) position. Therefore in this study, we sought to determine this by conducting three successive partial meniscectomies of the posterior horn of the medial meniscus (PMM) and measuring the laxity and AP position of the medial femoral condyle over a series of loading conditions following each resection. It was hypothesized that more than a 50% resection would result in significant changes in laxity and AP position equivalent to a 100% removal of the PMM.
Biomarker Identification Under Growth Factor Priming for Cartilage Tissue Engineering
Authors: Alegre-Aguarón Elena , Sampat Sonal R. , Hampilos Perry J. , Bulinski J. Chloë , Cook James L. , Brown Lewis M. , Hung Clark T.
Published: July 2013

Adult articular cartilage has a poor healing capacity, which has lead to intense research toward development of cell-based therapies for cartilage repair. The destruction of articular cartilage results in osteoarthritis (OA), which affects about 27 million Americans. In order to create functional tissue, it is essential to mimic the native environment by optimizing expansion protocols. Cell passaging and priming with chemical or physical factors are often necessary steps in cell-based strategies for regenerative medicine [1]. The ability to identify biomarkers that can act as predictors of cells with a high capacity to form functional engineered cartilage will permit optimization of protocols for cartilage tissue engineering using different cell sources. Recent investigations have shown that chondrocytes and synovium-derived stem cells (SDSCs) are promising cell sources for cartilage repair [2,3]. The analysis of gene expression and comparative proteomics, which defines the differences in expression of proteins among different biological states, provides a potentially powerful tool in this effort [4]. The aim of this study was to investigate the impact of growth factor priming in 2D canine chondrocytes and SDSCs cultures by identifying differentially regulated biomarkers, which can correlate to functional tissue elaboration in 3D.
Valgus Knee Alignment, Not Step Width or Toe-Out Cause Reduced Knee Adduction Moment in the Healthy Obese
Authors: Blazek Katerina , Asay Jessica , Erhart-Hledik Jennifer , Andriacchi Thomas
Published: July 2013

Obesity is a strong risk factor for knee osteoarthritis (OA) [1], but the mechanism of OA initiation associated with obesity is not clear. Increases in ambulatory knee joint load due to obesity have been implicated as a cause of increased OA incidence, since an increased adduction moment has been associated with the severity and progression of medial compartment OA [2]. However, previous work has not consistently shown increases or decreases in the adduction moment in the obese. Step width and toe-out reduce the adduction moment [3] and are increased in the obese [4], suggesting that the adduction moment could also be reduced in the obese. Furthermore, obesity may be associated with knee malalignment, which may also alter the adduction moment. However, the cumulative effect of these gait alterations on the adduction moment is unclear, given the increased risk of medial knee OA in the obese. Understanding this interaction is important in understanding the link between obesity and knee OA.
Determination of In Situ Ankle Ligament Strains in Cases of High and Medial Ankle Sprains
Authors: Button Keith D. , Wei Feng , Meyer Eric G. , Fitzsimons Kathleen , Haut Roger C.
Published: July 2013

Ankle sprain is a common occurrence in sports, accounting for 10–30% of injuries [1]. While approximately 85% of ankle sprains are lateral ankle injuries, syndesmotic (high) and medial injuries typically result in more time off the field. In order to help limit or mitigate ankle injuries, it is important to understand the mechanisms of injury. While numerous biomechanical studies have been conducted to investigate ankle injuries, most of them are designed to study ankle fractures rather than sprains. Ankle sprains have been graded in the clinical literature and associated with the degree of damage to a ligament resulting from excessive strains [2]. Recently, there have been studies of lateral ankle sprain in laboratory settings [3,4] and based on investigation of game films [5], providing considerable insight into the mechanism of lateral ankle sprain. On the other hand, few biomechanical studies have been conducted on high and medial ankle sprains. A more recent study from our laboratory used human cadaver limbs to investigate such injuries [6]. The study showed that the type of ankle injury, whether medial or high, under excessive levels of external foot rotation depends on the extent of foot eversion [6]. Everted limbs showed isolated anterior tibiofibular ligament injuries (high ankle sprain) only, while neutral limbs mostly demonstrated deltoid ligament failures (medial ankle sprain). Additionally, the study documented grade II (partial tears) and grade III (ruptures) ligament injuries. While a computational ankle model has also been developed and validated to help understand the mechanisms of injury [7], it is a generic model. The objective of the current study was to develop computational, subject-specific models from those cadaver limbs and determine the levels of ligament strain generated in the medial and high ankle injury cases, as well as correlate the grades of injury with ligament strains from the computational model.
Articular Cartilage Wear Characterization With a Particle Sizing and Counting Analyzer
Authors: Oungoulian Sevan R. , Bortz Orian , Hehir Kristin E. , Zhu Kaicen , Hung Clark T. , Ateshian Gerard A.
Published: July 2013

The primary function of articular cartilage is to serve as the bearing material in diarthrodial joints, transmitting loads while minimizing friction and wear. The friction coefficient of cartilage has been characterized extensively in the literature, using standard measurements of normal and tangential forces acting across a sliding interface [1]. However, quantitative measurements of cartilage wear have proven to be more challenging, with only a few studies having reported such measurements. The primary quantitative approaches proposed to date include biochemical assaying of cartilage and test solutions [2], and characterization of changing articular layer thickness [3] and surface roughness [4]. One study examining polyethylene wear debris in hip arthroplasty reported the use of an automated particle analyzer [5]. The aim of this study was to test the hypothesis that latest-generation particle analyzers are capable of detecting cartilage wear debris generated during in vitro loading experiments that last 24 h or less, by producing measurable content significantly above background noise levels. The longer-term objective of our studies is to test the hypothesis that elevated interstitial fluid pressurization, which is known to reduce the friction coefficient of cartilage [6], also reduces cartilage wear.
Changes in Conduit Pulmonary Arterial Static and Dynamic Mechanical Properties During Severe Hypoxic Pulmonary Hypertension
Authors: Wang Zhijie , Lakes Roderic S. , Chesler Naomi C.
Published: July 2013

Pulmonary hypertension (PH) is a complex disorder that manifests as abnormally high blood pressure in the vasculature of the lungs. The chronic structural and mechanical changes in the proximal pulmonary artery (PA) associated with PH include smooth muscle cell hypertrophy and proliferation, accumulation of extracellular matrix (ECM) protein and increased stiffness1–4. Recent evidence has shown that conduit PA stiffness is a strong predictor of mortality in pulmonary arterial hypertension5,6. This suggests a potential association between large PA biomechanics and right ventricle failure.
Forces and Flow: Implications for Pressure Ulcers Demonstrated Through the Use of Magnetic Resonance Angiography
Authors: Manorama Abinand , Bush Tamara Reid , Meyer Ronald , Wiseman Robert
Published: July 2013

The combination of normal and shear forces applied to the skin over time can be detrimental to individuals with compromised health, such as the elderly or spinal-cord injured. These forces are factors associated with the formation of deep, penetrating wounds called pressure ulcers.
Contribution of the Minor Chain Type IV Collagen Network to the Mechanics of the Ocular Lens Capsule
Authors: Gyoneva Lazarina , Segal Yoav , Dorfman Kevin D. , Barocas Victor H.
Published: July 2013

The ocular lens capsule (LC) is a specialized basement membrane which completely surrounds the lens. The LC serves as an attachment point for lens epithelial and fiber cells, controls lens solute and water transport, and makes accommodation possible [1]. It is primarily composed of type IV collagen (65% of dry weight), laminin, nidogen, and proteoglycans, of which type IV collagen is the main-tension resisting element [1,2]. Collagen IV monomers organize into polygonal planar networks resembling chicken wire (Fig.1) [3]. There are six different collagen IV monomers, labeled α1(IV) to α6(IV) each produced by a separate gene – COL4A1 to COL4A6. Monomers form triple helical protomers in a highly selective manner. In nature, only three monomer combinations have been discovered: the [α1(IV)]2α2(IV) protomer, referred to as the major chain, is found in all basement membranes; the α3(IV)α4(IV)α5(IV) protomer (minor chain) is found only in few basement membranes including the LC; the [α5(IV)]2α6(IV) protomer is very rare and will not be discussed further. Protomers of the same type assemble with one another to form separate networks which are known to have some differences [4]. For example, the minor chain network is more cross-linked than the major chain network. In a hereditary disease called Alport syndrome, the minor chain network is completely missing in males due to a mutation in the COL4A5 gene (located on the X chromosome) which prevents production of the α5(IV) monomer. Male Alport syndrome patients have significant ocular manifestations such as anterior lenticonus (protrusion of the lens), cataract, and even lens rupture [5] and they exhibit significant thinning of the LC. Because 1) the minor network is more cross-linked than the major network, 2) its absence affects lens shape, and 3) the LC displays pathological disruptions when it is missing, we theorize that its presence confers additional mechanical strength to the LC. Therefore, the objective of this study is to assess the contribution of the minor chain network to the mechanics of the LC.
Effect of Partial Medial Meniscectomy on the Interaction Between Primary and Secondary Knee Motion During Gait
Authors: Edd Shannon N. , Netravali Nathan A. , Giori Nicholas J. , Andriacchi Thomas P.
Published: July 2013

Meniscal injury is a well-known risk factor for osteoarthritis (OA); the leading treatment (meniscectomy) increases the risk for osteoarthritis four times over sixteen years [1]. Reports that meniscectomy patients display altered gait kinetics and kinematics post-operation [2,3] suggest altered gait mechanics as a potential link between meniscal resection and increased risk for OA. Specifically it has been suggested that altered gait is a pathway to OA by causing a shift in tibiofemoral cartilage contact location to unprepared regions, which leads to cartilage breakdown [4]. The altered gait mechanics of particular interest are secondary motions of the knee, including internal-external (IE) rotation and adduction angle. While previous research has shown there to be a decrease in early stance (ES) and mid-stance (MS) range of motion (ROM) in knee flexion angle along with decreased peak extension of the affected versus contralateral limb, there is a lack of data relating the interaction between primary (flexion) and secondary (IE rotation and adduction angle) motions of the knee in the meniscectomy population [2,3]. Yet this information is important for understanding the ambulatory conditions associated with knee OA following meniscectomy.
Elucidation of Microstructural Interactions Between Collagen and Non-Fibrillar Matrix in Soft Tissue Using a Coupled Fiber-Matrix Model
Authors: Zhang Lijuan , Lake Spencer P. , Lai Victor K. , Barocas Victor H. , Shephard Mark S.
Published: July 2013

The mechanical properties of soft connective tissues are governed by their collagen fiber network and surrounding non-fibrillar matrix (e.g., proteoglycans, cells, elastin, etc.). In order to understand how healthy tissues function, and how properties change in injury and disease, it is necessary to quantify the mechanical response of both the collagen network and the non-fibrillar matrix (NFM), as well as the nature of the interaction between these tissue constituents. Using collagen-agarose co-gels as a simple experimental tissue analog system, we have demonstrated how NFM contributes to the mechanical and organizational properties of soft tissues in indentation and tension [1–2]. Furthermore, we used a network-based microscale model to examine how specific NFM properties alter the response of fiber-matrix composites under load [3]. This model fit our experimental data well and provided insight into the role of NFM in tensile mechanics. Since it was constructed according to the conventional approach of superposition of the two constituents (collagen network and NFM), however, the model could not specifically examine local interactions between collagen fibers and the surrounding NFM, which could be critical in assessing tissue damage or cell-matrix interactions. Therefore, we developed and evaluated a fiber-matrix modeling scheme to characterize the microstructural interactions between tissue constituents, as well as to quantify the role of individual tissue components in the behavior of soft tissues under tensile load. For validation, the new model (‘coupled’) was compared to our previous model (‘parallel’) and to experimental co-gel data.
Prevascularized, Co-Culture Model for Breast Cancer Drug Development
Authors: Marshall Lauren , Löwstedt Isabel , Gatenholm Paul , Berry Joel
Published: July 2013

The objective of this study was to create 3D engineered tissue models to accelerate identification of safe and efficacious breast cancer drug therapies. It is expected that this platform will dramatically reduce the time and costs associated with development and regulatory approval of anti-cancer therapies, currently a multi-billion dollar endeavor [1]. Existing two-dimensional (2D) in vitro and in vivo animal studies required for identification of effective cancer therapies account for much of the high costs of anti-cancer medications and health insurance premiums borne by patients, many of whom cannot afford it. An emerging paradigm in pharmaceutical drug development is the use of three-dimensional (3D) cell/biomaterial models that will accurately screen novel therapeutic compounds, repurpose existing compounds and terminate ineffective ones. In particular, identification of effective chemotherapies for breast cancer are anticipated to occur more quickly in 3D in vitro models than 2D in vitro environments and in vivo animal models, neither of which accurately mimic natural human tumor environments [2]. Moreover, these 3D models can be multi-cellular and designed with extracellular matrix (ECM) function and mechanical properties similar to that of natural in vivo cancer environments [3].
Microfluidic Cell Arrays to Mimic 3D Tissue Microenvironment
Authors: Dereli-Korkut Zeynep , Wang Sihong
Published: July 2013

We developed a functional high throughput 3D microfluidic living cell array (MLC) for anti-cancer drug screening and mechanism discovery. Contemporary drug screening methods suffer from low sample throughput and lack of abilities of mimicking the 3D microenvironment of mammalian tissues. The poor performance of anti-cancer drugs limits the efficacy at controlling the complex disease system like cancer. Systematic studies of apoptotic signaling pathways can be prominent approaches for searching active and effective treatments with less drug resistance. Hence, innovative bio-devices are needed to represent tumor microenvironment to understand the molecular signatures of apoptosis for testing new anticancer therapies targeting apoptosis. Our novel 3D MLC design is the prototype of a high-throughput drug screening platform targeting apoptotic signaling pathways.
Altered Internal Strain Distributions in Adult Ovine Cartilage Before and After Full-Thickness Cartilage Defect
Authors: Chan D. D. , Butz K. D. , Nauman E. A. , Dickerson D. A. , Neu C. P.
Published: July 2013

Articular cartilage and surrounding soft tissues in the knee are important to normal joint function. However, disease, trauma, and progressive degeneration can alter the function of the joint, often changing the distributions of tissue deformation through the tissues of the knee [1], and lead to advanced osteoarthritis [2]. Knowledge of the mechanical properties of the soft tissues in the knee is important to characterize both normal and damaged joints. Additionally, the ability to restore the strain distribution of damaged regions to accepted normal values could be used as a measure of success of a tissue engineering solution. Noninvasive imaging technologies, such as magnetic resonance imaging (MRI), can be used to study normal tissue, detect tissue damage, and monitor both degeneration and the progress of repair treatments.
Strong Coupled Fluid-Structure Interaction Simulation of Cerebrovascular System Using Multi-Scale Model
Authors: Katagiri Kengo , Krdey Absei , Yamamoto Sota , Oshima Marie
Published: July 2013

Cerebrovascular disorder such as subarachnoid hemorrhage is the number 3 cause of death in Japan [1]. Initiation and growth of those diseases depend on hemodynamic factors such as Wall Shear Stress (WSS) or blood pressure induced by blood flow [2]. Therefore the information on the magnitude and the distribution of WSS is important to predict the consequences.
Mechanical Response of Human Knee Joint to Sinusoidal Compression: Influence of Fluid Pressurization in Soft Tissues
Authors: Dabiri Yaghoub , Li LePing
Published: July 2013

The mechanical response of the knee joint has been simulated using finite element methods with elastic material models [1–4]. Fluid pressurization in articular cartilage and menisci has not been considered in the anatomically accurate joint modeling until recently [5–7]. We have recently considered stress relaxation and creep behavior of human knees. The objective of the present study was to investigate the mechanics of the femoral cartilage under cyclical knee compression. We are particularly interested in the determination of loading versus unloading patterns for the fluid pressure and flow, as well as the influence of the loading frequency on the fluid pressurization.
Multiscale Model of Airflow in Healthy and Emphysema Rat Lungs
Authors: Oakes Jessica M. , Marsden Alison L. , Grandmont Celine , Darquenne Chantal , Vignon-Clementel Irene E.
Published: July 2013

An investigation of airflow is essential in understanding the fate of aerosol particles in healthy and diseased lungs. Emphysema is a heterogeneous disease that results in destroyed pulmonary tissue, alveolar space enlargement and oxygen delivery impairment. A numerical model of the entire lung will assist in understanding the ventilation and aerosol deposition changes that occur with emphysema. The pulmonary airflow cannot realistically be solved in 3D for the entire lung, therefore multiscale techniques must be used to simulate dynamics by coupling 3D and 0D models.
Modeling of Coated Biodegradable Stents
Authors: Debusschere Nic , De Beule Matthieu , Segers Patrick , Verhegghe Benedict , Dubruel Peter
Published: July 2013

A bioresorbable stent supports the stenosed blood vessel during the healing period after coronary angioplasty and then gradually disappears. Unlike permanent stents, the biodegradable stent forms no obstacle for future interventions. Moreover, the degradable stent material presents an ideal vehicle for local drug delivery. Long term side effects inherent to drug eluting stents such as in-stent restenosis and late stent thrombosis might be avoided [1]. To date, several bioresorbable stents are being developed or are currently being tested in clinical trials. Two classes of biomaterials are being used in biodegradable stent technology: biodegradable polymers and bioerodible metal alloys. Polymers can be tailored to have a well-defined degradational behaviour but have relatively poor mechanical properties. Biocorrodible metals such as magnesium alloys have good mechanical characteristics but display a more complex an less predictive degradational behaviour. A biocorrodible metallic stent coated with a biodegradable polymer might be able to combine the benefits of both metallic and polymeric biodegradable stents. Finite element modelling can play an important role in the study of nevel stent designs. To correctly simulate the behaviour of degradable stents a material model must be developed that incorporates the effect of degradation on all material characteristics. In case of a coated biocorrodible magnesium stent this includes corrosion modelling, the effect of the coating and the influence of mechanical loading on the corrosion rate.
Knee Joint Rotation and Loading During Turning After Anterior Cruciate Ligament Reconstruction
Authors: Wang Hongsheng , Fleischli James E. , Zheng Nigel
Published: July 2013

Abnormal knee movement during dynamic activities after ACL rupture has been reported[1–3]. A reconstructive surgery is recommended by orthopedic surgeons to restore joint stability. After ACL reconstructive surgery and rehabilitation that follows the normal knee movement has not been fully restored, especially for the nonsagittal plane rotations, during walking and high demanding activities (stairs, pivoting, cutting, jump and landing, etc.) [2, 4–10].
Cytoskeletal Fluidization and Resolidification are Required for Reorientation of Endothelial Cells
Authors: Krishnan Ramaswamy , Canovic Elizabeth Peruski , Iordan Andreea L. , Pirentis Athanassios P. , Rajendran Kavitha , Manomohan Greeshma , Smith Michael L. , Butler James P. , Fredberg Jeffrey J. , Stamenović Dimitrije
Published: July 2013

Vascular endothelial cells are subjected to routine mechanical stretch. In response, cellular microstructures rearrange locally as the cell body realigns globally [1–5]. These responses, which underlie the vital functions of the endothelium, are often explained in terms of upstream mechanosensing and downstream cell signaling [2–5].
Mechanotransduction of Primary Cilia in Lung Adenocarcinoma
Authors: Patel Sagar S. , Natarajan Ramesh , Heise Rebecca L.
Published: July 2013

Lung cancer causes more than 1 million deaths worldwide annually [1]. In a recent study by the American Cancer Society in 2011, more than 221,000 new cases of lung cancers were reported [2]. Out of these, the mortality rate was found in roughly 70% of the cases [2]. Lung cancer is divided into two major categories: small cell and non-small cell. In the United States, non-small cell lung cancer accounts for 85% of all lung cancers and is considered the most common type of lung cancer [2]. It is usually resistant to chemotherapy, therefore making it extremely difficult to treat [3]. Furthermore adenocarcinomas, a type of non-small cell lung cancer, occur towards the periphery of the lungs and are the most common type accounting for 40–45% of all lung cancer cases [3]. Epithelial cells in the healthy lungs undergo stresses during inhalation and expiration of normal breathing. In addition to the forces of normal breathing, lung cancer cells may also experience abnormal mechanical forces due to pre-existing lung diseases such as asthma, bronchitis and chronic obstructive pulmonary disease or other tumor associated structural changes. These conditions can significantly alter the structure of the lungs and cell phenotype [4]. The change in the structure of the lungs affects the mechanical environment of the cells. Changes in extracellular (ECM) stiffness, cell stretch, and shear stress influence tumorigenesis and metastasis [5]. One mechanism through which the cells sense and respond to the cellular mechanical environment is through the primary cilia [6–7]. Primary cilia are non-motile, solitary structures formed from the cellular microtubules and protrude out of each cell. They have also been shown to play an important role in facilitating common cancer signaling pathways such as Sonic Hedgehog and Wnt/β-catenin signaling [8–9]. The objective of this study was to test the hypothesis that lung cancer cells respond to mechanical stimuli with the formation of primary cilia that are necessary for 3 hallmarks of tumor progression: proliferation, epithelial mesenchymal-transition, and migration.
The Effect of Geometry on Patellar Tracking After TKA During Simulated Gait
Authors: Ferris Lauren , Shalhoub Sami , Maletsky Lorin
Published: July 2013

Abnormal patellar tracking is the main cause of patellofemoral disorders and revision surgeries after total knee replacements (TKA) [1]. The decision to resurface or keep the natural patella has been an ongoing debate when performing TKA since patella morphology and femoral implant design affects patello-femoral (PF) kinematics during gait [2]. A previous study investigated the effects of resurfacing versus unresurfacing the patellae inter-specimen [3]. Error introduced in subject to subject studies can be reduced by performing a cadaveric study where PF kinematics for different patellae geometries are implanted in the same specimen. The purpose of this study was to measure PF kinematics in vitro during three simulated gait cycles with natural, unresurfaced, an anatomical design, and medialized dome patellae to determine the effects of different patellae design and gait cycles on PF kinematics.
CFD Challenge: Experimental Benchmarking Data for the Pressure Drop Across a Cerebral Aneurysm Model
Authors: Fahy Paul , Walsh Michael , Loth Francis , Ene Florentina , Delassus Patrick , Morris Liam
Published: July 2013

Since 2006, the GMedTech biomedical research centre in the Galway Mayo Institute of Technology (GMIT) in the west of Ireland has developed capabilities for generating physiological type flow conditions through realistic vascular models based on medical images. The GMedTech centre has designed and developed a number of fully controlled and instrumented synchronised experimental test systems for testing in the abdominal aorta, coronary, venous and intracranial vessels with and without associated disease types. The experimental testing was performed by PhD candidate Paul Fahy and his supervisors Dr. Liam Morris and Dr. Patrick Delassus.
Engineering Magnetic Nanomaterial Production in Magnetotactic Bacteria Through Gene Regulation
Authors: Wilson Mary E. , González Lina M. , Ruder Warren C. , LeDuc Philip R.
Published: July 2013

Magnetotactic bacteria endogenously synthesize intracellular magnetic nanoparticles (magnetosomes); however, little is known regarding the genetic regulatory networks that control magnetosome production. In this paper, we explore the genetic response of Magnetospirillum magneticum strain AMB-1 to an applied electromagnetic field as a means to identify genes activated by magnetic stimulation. The expression of magnetosome island, flagellar and cytoskeletal genes was found to be differentially altered by magnetic stimulation at short and long times points. These results indicate previously uncharacterized endogenous gene network modules that could be exploited to engineer magnetic bacteria as magnetic nanomaterial producing-machines through gene regulation.