bluuebunny/crossref_metadata_2025 huggingface dataset:
Augmentation Devices for Rotator Cuff Repair
Authors: Derwin Kathleen A. , Iannotti Joseph P.
Published: July 2013

Rotator cuff tears affect 40% or more of those over age 60 and are a common cause of pain and disability. Surgical repairs have high failure rates that range from 20 to 90%. Currently, scaffolds derived from various natural and synthetic biomaterials are being marketed as augmentation devices for rotator cuff repairs at the time of surgery 1–3. The US Food and Drug Administration (FDA) has cleared these devices “to support soft tissues where weakness exists” but not “to provide the full mechanical strength for the tendon repair”. Based on the mechanical connotation of their intended use, it is commonly believed that when applied appropriately, these devices may provide some degree of load sharing of forces across the tendon repair site and thus decrease the likelihood of tendon re-tear.
Strain and Substrate Stiffness Affect Calcium Accumulation in Aortic Valve Interstitial Cells
Authors: Hutcheson Joshua D. , Sewell-Loftin M. K. , Merryman W. David
Published: July 2013

The progression of aortic valve (AV) disease is often characterized by the formation of calcific nodules on thickened AV leaflets, limiting the biomechanical function of the valve. Calcification is a major problem that often leads to the failure of bioprosthetic replacement valves [1]. In these cases, the association of extracellular Ca2+ with phosphates remaining in cellular debris within the decellularized scaffolds has been proposed to lead to the nucleation and growth of Ca3(PO4)2 nodules. In native tissue, calcification is thought to be a more active process involving AV interstitial cells (AVICs). The exact molecular mechanisms that lead to the formation of these calcific nodules in native tissue remain unclear; however, AVICs have been shown to form nodule-like structures in vitro through differentiation to a phenotype with osteogenic character [2]. Additionally, in vitro nodules are characterized by activated smooth muscle α-actin positive AVICs and high levels of apoptosis [2–3]. Mechanical strain has also been shown to influence nodule formation in excised AV leaflets [4]. Intracellular Ca2+ exhibits mechanodependency in cultured cells [5], and heightened levels of intracellular Ca2+ have been shown to be associated with apoptosis in many cell types [6] In this study, we assess the role of mechanically-induced changes in intracellular calcium and its function in modulating AVIC behavior. We hypothesized that intracellular Ca2+ will increase in strained AVICs and that over time, this will lead to apoptosis. We believe that the results from this study will help illustrate the mechanotransductive role of Ca2+ in AVICs and may elucidate early cellular changes that lead to AV calcification.
The Relationships Among Spatiotemporal Gene Expression, Histology, and Biomechanics Following Full-Length Injury in the Murine Patellar Tendon
Authors: Dyment Nathaniel A. , Kazemi Namdar , Aschbacher-Smith Lindsey E. , Barthelery Nicolas J. , Kenter Keith , Gooch Cynthia , Shearn Jason T. , Wylie Christopher , Butler David L.
Published: July 2013

Tendon and ligament injuries present a considerable socioeconomic impact as close to 50% of the 32 million musculoskeletal injuries in the US per year include these structures [1]. The inadequate healing in these tissues requires novel treatment modalities. Improving tendon tissue engineering dictates that we better understand the process of natural adult tendon healing. Type-I (Col1) and Type-II (Col2) collagens are important structural proteins in tendon as Col1 is the main collagen type found in the tendon midsubstance while Col2 is expressed at the insertion into bone during development, growth, and healing [2–3]. Expression of Col1 and Col2 has typically been analyzed via qPCR, western blotting, and immunohistochemistry (IHC) during healing. However, the temporal expression of these genes is still poorly understood on a cell-by-cell basis. Our lab has previously studied patellar tendon (PT) healing in NZW rabbits [4]. While the NZW rabbit allows for controlled injuries and accurate biomechanical assessment of healing, it lacks the genetic power that is offered in the mouse. Therefore, pOBCo13.6GFPtpz (Col1) and pCol2ECFP (Col2) double transgenic (DT) reporter mice were created to track spatiotemporal gene expression. Thus, the objectives of this study were to monitor changes in: 1) spatiotemporal Col1 and Col2 gene expression patterns, 2) tissue morphology, and 3) healing biomechanics following a full-length, central PT injury in Col1/Col2 DT mice and to compare these natural healing results to contralateral surgical shams and normal PT in age-matched controls.
Creating a Low Volume Model of Occlusive Thrombosis
Authors: Para Andrea N. , Ku David
Published: July 2013

Heart disease is the leading cause of death in industrialized countries. Heart attacks and strokes can cause mortality within an hour following plaque rupture. Unfortunately, as it is impossible to study heart attacks in real time, little is known about the mechanism which contributes to mortality. The mechanism of thrombosis under high shear is currently in dispute. Some investigators have shown that GPIIb/IIIa is important in stabilizing a thrombus under high shear conditions.[1] We have independently shown occlusive thrombosis in a gravity-fed tubular stenosis is predicated on a delayed phase of Rapid Platelet Accumulation (RPA) that occurs only at pathologically high shear rates with fast occlusion times consistent with Acute Coronary Syndrome.[2] However, Ruggeri has recently shown that platelet deposition and aggregation can occur at high shear model independent of GPIIb/IIIa which must be activated for binding.[3] Thus, the role of GPIIb/IIIa on high shear thrombosis to occlusion is not known.
Calcium Efflux From Bone Matrix in Response to Mechanical Loading
Authors: Sun Xuanhao , McLamore Eric S. , Porterfield D. Marshall , Akkus Ozan
Published: July 2013

Bone is known for its ability to self-repair the microdamage and actively adapt to its mechanical environment, both of which are under the coordination of bone cells. Mechanical cues are sensed by cells and converted into cellular events in a process called mechanotransduction [1]. Most theories of mechanotransduction are based on direct stimulus of cell surface receptors by substrate deformation, fluid shear and/or hydrostatic pressure [2]. Yet, mechanical stimulus may come to affect cell response indirectly, via pathways which alter the pericellular niche. Such indirect pathways of mechanotransduction are not well-investigated for bone.
A Bioactive Peptide Grafted Scaffold for Peripheral Nerve Regeneration
Authors: Masand Shirley , Chen Jian , Schachner Melitta , Shreiber David I.
Published: July 2013

Despite this innate regenerative potential of the peripheral nervous system, functional recovery often remains incomplete, especially as the severity of injury increases. This has been attributed to a number of sources including the ingrowth of fibrous scar tissue, lack of mechanical support for emerging neurites, and the malrouted reinnervation of neurites towards inappropriate targets. While research in the field is broad, it is generally accepted that an optimal nerve guidance conduit to encourage regeneration should include both biological and mechanical support for emerging neurites and glia.
Effect of rhPDGF-BB-Coated Sutures on Tendon Healing in a Rat Model: A Histological and Biomechanical Study
Authors: Cummings S. , Dines J. , Hee C. K. , Kestler H. K. , Roden C. M. , Shah N. , Razzano P. , Dines D. , Chahine N. , Grande D.
Published: July 2013

Delivering growth factors to the site of injury using a coated suture delivery method has been investigated recently as a means to augment tissue repair [1]. This is a practical approach for growth factor delivery, as sutures are the method of choice for most orthopaedic surgeons for soft tissue repairs. One advantage of growth factor-coated sutures in tendon repair is the potential to accelerate healing in vivo, thereby improving the outcome of the repair. In particular, platelet-derived growth factor-BB (PDGF-BB) is a well characterized wound healing protein known to be chemotactic and mitogenic for cells of mesenchymal origin, including tenocytes, and has been shown to improve healing when applied to animal models of tendon injury [2,3]. The aim of this study was to compare the quality of the tendon repair at four weeks post treatment with sutures coated with varying concentrations of rhPDGF-BB, relative to buffer-coated suture repairs.
Anchorage: Dependent Persistent Alignment of Perfused Microvasculature in Implanted Tissue Constructs
Authors: Krishnan Laxminarayanan , Chang Carlos C. , Reese Shawn , Williams Stuart K. , Weiss Jeffrey A. , Hoying James B.
Published: July 2013

One of the challenges in engineering complex artificial tissue constructs, with defined matrix and cellular architecture, is the formation of a viable microcirculation within them, that inosculates with the host vasculature and matures into a functional microvascular bed. Current methods based on complex cell patterning in 2-D or 3-D matrix systems rely on ‘printing’ cells or patterns of cells on/ in a substrate, direct culture on patterned substrates, or endothelialization of decellularized vessels. We are now beginning to understand the effects of the microenvironment on microvascular constructs. Flow induced remodeling and maturation of angiogenic microvasculature and changes in functional characteristics when co-implanted with astrocyte precursors strongly suggests a role for the local environment in determining characteristics of the microvascular bed [1, 2]. Chang et al. have shown that neovascular networks from microvessels pre-aligned by direct-bioprinting in a collagen matrix, retain alignment when cultured in vitro, but lose alignment on implantation in vivo [3]. Though unloading of mechanically loaded tissue influences cell behavior [4], it does not explain this loss of orientation after implantation, of previously unloaded constructs. Implanted constructs have an additional level of complexity in the form of network revision and maturation with blood flow. We hypothesize that the local mechanical microenvironment, in addition to flow, dictates network morphology in vivo. This study compares the changes in pre-aligned microvascular networks implanted with and without anchorage.
Analysis of Experimental IOP-Induced Scleral Deformations at the Sub-Micrometer Scale Using Electronic Speckle Interferometry
Authors: Fazio Massimo A. , Bruno Luigi , Grytz Rafael , Downs J. Crawford
Published: July 2013

The retinal ganglion cell axons carry visual information, and pass through the optic nerve head (ONH) as they traverse from inside the eye to the brain. The ONH is the site of axonal damage in glaucoma, the second leading cause of blindness in the world, and ONH biomechanics is hypothesized to play a crucial role in the development and progression of the disease. The load bearing tissues of the ONH insert into the surrounding sclera, which provides the boundary conditions for this important structure. It is therefore important to develop accurate experimental techniques to measure scleral shell deformations under intraocular pressure (IOP) loading that can be used to drive constitutive and computational models of scleral biomechanics. The overall goal of this project is to better understand the role of ocular biomechanics in the development of glaucoma by constructing eye-specific finite element models of the posterior pole and ONH.
The Effect of Cyclic Hydrostatic Pressure on the Functional Development of Cartilaginous Tissues Engineered Using Bone Marrow Derived Mesenchymal Stem Cells
Authors: Meyer Eric G. , Buckley Conor T. , Kelly Daniel J.
Published: July 2013

Articular cartilage has a poor capacity for repair. Of the many procedures available to the orthopaedic surgeon, osteochondral grafting is the only technique which reliably produces hyaline cartilage within a defect.1 Bone marrow derived mesenchymal stem cells (MSCs) are an interesting alternative to harvesting cartilage grafts for chondrocytes as they also have the ability to produce cartilaginous tissues in vitro. This suggests that if tissue engineering strategies could be used to develop cartilaginous grafts with mechanical properties approaching that of normal articular cartilage, then hyaline tissue could be regenerated. Of concern with such approaches are reports that the mechanical properties of cartilaginous tissues engineered using MSCs are inferior to that engineered using chondrocytes derived from articular cartilage, although recent studies have demonstrated that adult equine MSCs produce a cartilaginous tissue mechanically superior to that derived using animal-matched adult chondrocytes.2
Classification of Vulnerable Plaques in Human Coronary Arteries Using High Resolution Micro-CT Imaging
Authors: Kelly Adreanne , Maldonado Natalia , Vengrenyuk Yuliya , Fallon John T. , Virmani Renu , Cardoso Luis , Weinbaum Sheldon
Published: July 2013

Sixty percent of the more than 500,000 cases of acute coronary syndrome that lead to death are due to plaque rupture. Understanding the mechanisms of rupture is important to predicting the risk of rupture. Determining these mechanisms begins with acquiring an accurate visualization of the arteries containing fiberoatherotic lesions or fibroatheroma.
Impedance to Cerebrospinal Fluid Flow in the Cervical Spinal Canal is Dominated by Geometric Complexity
Authors: Shaffer Nicholas , Loth Francis , Wieben Oliver , Rocque Brandon , Iskandar Bermans , Oshinski John
Published: July 2013

In a fluid system, longitudinal impedance (LI) is the impedance per unit length of a conduit. Its magnitude depends on conduit geometry and the mechanical properties of both the fluid and conduit. In the context of vein grafts, LI has been shown to correlate with vein graft size and graft patency at one year from surgery [1]. More generally, LI has been shown to be consistent over a wide range of physiological flows [2]. Due to its ability to characterize the effect of geometry on flow in a conduit, LI may be useful in examining differences between a healthy spinal canal and one affected by Type I Chiari malformation (CMI). CMI is a complex disorder of the craniospinal system classically characterized by herniation of the cerebellar tonsils of 3–5 mm past the foramen magnum [3], which has proven difficult to properly diagnose as the associated neurological symptoms may overlap with the symptomatology of other disorders. Current methods of quantifying CMI severity, such as cerebellar tonsil herniation depth, do not necessarily correlate with symptom severity. Likewise, studies that have sought to hydrodynamically analyze CMI by measuring cerebrospinal fluid (CSF) velocity have yielded mixed results. We hypothesized that the severity of obstruction to CSF flow in the CMI-affected cervical spinal canal can be quantified and compared by calculation of LI.
Anterior Chamber Angle and Iris-Lens Contact Alteration During Pupillary Dilation
Authors: Jouzdani Sara , Amini Rouzbeh , Barocas Victor H.
Published: July 2013

The aqueous humor (AH) provides oxygen and nutrients for the avascular ocular tissue specifically, the cornea and lens. AH is secreted by the ciliary body into the posterior chamber, passes through pupil, and drains into the anterior chamber (Fig. 1a). Resistance to the aqueous outflow generates the intraocular pressure (IOP), which is 15–20 mmHg in the normal eyes.
Characterization of a Biomechanical Animal Model for Intact Knee Kinematics and ACL Function Using 6-DOF Robotic Technology
Authors: Boguszewski Daniel V. , Herfat Safa T. , Wagner Christopher T. , Butler David L. , Shearn Jason T.
Published: July 2013

Anterior cruciate ligament injury (ACL) affects an estimated 250,000 people annually [1]. Unfortunately, even with ACL reconstruction, the likely prognosis is long-term osteoarthritis (OA) [2]. Many strides have been made in attempting to understand and improve this outcome. The use of robotic technology has provided an avenue for researchers to examine the ACL’s role in knee joint stability in all six anatomical degrees of freedom (DOF) [3]. The overall goal of our lab robotics research is to use this technology to understand ACL function during activities of daily living (ADLs) in hopes of developing a biomechanical animal model which can be used as a preclinical tool to design new repair methods and materials. We have examined three species (ovine, porcine, and human), measuring all forces and moments produced from displacement control motion paths developed for cyclic testing in a robotic system (KUKA; KR210). This information will provide a basis for comparing intact knee biomechanics and ACL function across species. With these robotic inputs, we have performed a series of studies to aid in the development of a biomechanical model of the human knee.
Computational Analysis of Adhesion Dynamics in the Eustachian Tube During Inflammatory Otitis Media
Authors: Sheer Francis J. , Ghadiali Samir N.
Published: July 2013

Otitis Media (OM) is an inflammation of the middle ear (ME) that is the most commonly diagnosed childhood illness and the cost of treating OM has been estimated at four billion dollars annually. [1] The onset of OM is typically due to bacterial/viral infections that cause tissue swelling, rapid ME gas exchange and painful sub-ambient ME pressures. Normally, periodic openings of the ET are used to relieve ME pressures. However, the up-regulation of various adhesion proteins within the ET lumen make it difficult for the surrounding muscles to open the ET. The goal of this study is to use computational models to investigate how changes in adhesion dynamics during inflammation influence ET function in three different patient populations: healthy adults, normal children, and CP infants. We have developed a multi-scale computational models of the ET based on histo-morphological data obtained in each population. Adhesive forces within the lumen are modeled as non-linear, reputable spring elements. These models indicate that tissue morphology and mechanics can significantly influence the ET’s response to inflammatory adhesion forces. Specifically, changes in mucosal tissue stiffness and TVP muscle forces are most effective in overcoming inflammatory adhesion forces.
Evaluation of Acellular Mitral Valve Scaffolds: Anterior Leaflet, Posterior Leaflet, and Chordae Tendineae
Authors: Wang Bo , McCallum Dustin , Williams Lakiesha , Liao Jun
Published: July 2013

Myxomatous mitral valve (MV) disease is common in North America with an incidence of 1–2%. The abnormal valvular tissues in the myxomatous MV often causes mitral valve regurgitation, which requires surgical repair or replacement to prevent the reversal of blood flow from the left ventricle to the left atrium. A recent study shows that, although with an impressive initial durability, there is an increasing recognition of the reoccurrence of significant MR. For MR intervention with better long term durability, an increasing interest in MV tissue engineering has emerged recently. Another need for tissue engineered MV is from the treatment of congenital heart valve diseases. The current repair or replacement using small non-viable heart valve prosthesis (mechanical or bioprosthetic valves) cannot avoid the risky multiple valve replacement operations along with children’s growth. Therefore, the development of a living tissue engineered MV would greatly benefit both pediatric and adult MV disease population.
Effect of Trabecular Architecture on Transferring Load/Impact to the Brain: A Local Model of Single Trabecula
Authors: Saboori Parisa , Sadegh Ali
Published: July 2013

In this paper the mechanotransduction of the external load through the trabeculae in the subarachnoid space (SAS) was investigated. This has been accomplished by employing the results of our animal studies, i.e. the histology and architecture of trabeculae, and by creating local models consist of a trabecula. It is concluded that the trabeculae are mainly configured as an upright tree-like shaped, where the branches are attached to the pia mater and the stems are attached to the arachnoid. The result of the analysis reveal that said configuration of the trabeculae creates less strain in the brain when the head in subjected to external loads, and thereby damps the impact.
Elastic Properties of the Human Umbilical Cord in Preeclampsia
Authors: Dodson Reuben B. , Hunter Kendall S. , Ferguson Virginia L.
Published: July 2013

Maternal diseases of pregnancy have been found to detrimentally affect the fetal circulatory system, with consequences lasting well into adulthood. In 1995, Barker introduced the idea that major disorders of adult life (including coronary heart disease, hypertension, stroke and diabetes) arise not only through an interaction between factors in our lifestyle, such as a high-fat diet, obesity and smoking, and a genetically determined susceptibility but also through development in utero [1]. Epidemiological evidence continues to support the notion that adult cardiovascular disease (CVD) has fetal origins [2–5].
Extending Standard Rotational Rheometry for Small, Irregular, Anisotropic Tissues and Gels
Authors: Cirka H. , Farr W. , Koehler S. , Billiar K.
Published: July 2013

Quantification of the viscoelastic properties of soft tissues and protein gels is vital to the understanding of normal tissue development and disease progression and for evaluating the cell-mediated remodeling of fibrous protein-based engineered tissues (e.g., collagen, fibrin). Rotational (shear) rheometers are theoretically well suited for characterizing the storage and loss modulus of such soft gels; however, standard “geometries” used in such devices require relatively large, homogeneous samples to generate sufficient torque for accurate analysis of very soft materials, and the analysis generally assumes linear isotropic viscoelastic behavior. Newly formed tissues and biological protein gels such as blood clots are often small, soft (low stiffness), irregularly shaped, anisotropic, and difficult to handle. The aim of this work is to develop a method that will allow the accurate characterization of small, irregular protein gels utilizing an industry-standard rheometer.
Delivering Stem Cells to the Heart on Biological Sutures: Effects on Regional Mechanical Function
Authors: Guyette Jacques , Tao Zewei , DeMartino Angelica , Kuhn Melissa , Rolle Marsha , Pins George , Gaudette Glenn R.
Published: July 2013

Heart failure (HF) affects over 5 million people in the US alone,1 costs society over $10B per year in medical care costs,2 and is the single most common hospital discharge diagnosis.3 Despite our advances in many areas of cardiovascular disease, we have made little progress in treating HF,4 largely due to the fact that few treatments actually aim to treat myocardial infarction (MI), which is the underlying cause of most cases of HF. Once a patient exhibits HF, their long-term survival is in jeopardy, exhibiting less than 50% probability of survival 5 years after diagnosis.4
Rotational Acceleration and Velocity Associated With Concussion in Humans
Authors: Rowson Steven , Duma Stefan M.
Published: July 2013

Kinematic parameters of the head are used to predict brain injury because they are thought to be indicative of the inertial response of the brain. Although all injury metrics used to predict head injury in industry are based on linear acceleration, brain injury is widely believed to be caused by the complex interaction between linear and angular kinematics. Previous research investigating angular kinematics have focused on animal models, where data cannot be directly applied to humans [1, 2]. Optimally, these data would be derived from humans. There are an estimated 1.6 to 3.8 million sports-related occurring annually in the United States [3]. Football’s high incidence of concussion provides a unique opportunity to collect biomechanical data to characterize this injury. By instrumenting and observing a population that is at high risk for concussion (football players), data characterizing concussion can be collected in a natural and ethically sound manner. The objective of this study was to estimate the angular kinematics of the head associated with concussion using data collected from human volunteers.
Optimizing a Three Layered Electrospun Matrix to Mimic Native Arterial Architecture: Cellular and Mechanical Analysis
Authors: McClure Michael J. , Sell Scott A. , Simpson David G. , Walpoth Beat H. , Bowlin Gary L.
Published: July 2013

The architecture of the vascular wall is highly intricate and requires unique biomechanical properties in order to function properly. Native artery is composed of a mix of collagen, elastin, endothelial cells (ECs), smooth muscle cells (SMC), fibroblasts, and proteoglycans arranged into three distinct layers: the intima, media, and adventitia. Throughout artery, collagen and elastin play an important role, providing a mechanical backbone, preventing vessel rupture, and promoting recovery while undergoing pulsatile deformations [1]. The low-strain mechanical response of artery to blood flow is dominated by the elastic behavior of elastin which prevents pulsatile energy from being dissipated as heat [2]. Previous work has shown the ability to fabricate multi-layered electrospun scaffolds composed of polycaprolactone (PCL), elastin (ELAS), and collagen (COL), and their associated mechanical advantages. PCL was chosen, in this case, to provide mechanical integrity and elasticity, while elastin and collagen would provide further elasticity and bioactivity [3,4]. However, when the grafts were implanted in the descending aorta of a rat, cellular results were not as desirable as predicted. Therefore, further graft optimization was required. The hypothesis of this study was that blended polymers and biopolymers would be conducive for cellular attachment through specific integrin binding sites. To test this hypothesis, human umbilical artery smooth muscle cells (hUASMC) were seeded on electrospun PCL, COL, and ELAS blends for evaluation in a cell adhesion inhibition experiment.
Novel Extra Aortic Counterpulsation Device for Enhancing Cardiac Performance
Authors: Walsh Peter W. , McLachlan Craig , Ladd Leigh , Gillies R. Mark
Published: July 2013

Heart failure is the fastest growing cardiovascular disorder. Incidence is rising at a rate of approximately 2% to 5% in people over 65 years of age, and 10% in people over 75 years of age [1]. Over 13 Million people suffer from heart failure in the USA, Europe, Canada and Australia, and heart failure is a leading cause of hospital admissions and re-admissions in Americans older than 65 years of age [2]. The secondary heart pump system is the expansion and recoil of the aorta which reduces heart load and drives left coronary artery blood flow. Increases in aortic stiffness are a result of elastin degradation due to ageing and/or cardiovascular diseases such as atherosclerosis [3–5], which increase heart load and pulse pressure [6–10]. Significantly higher aortic stiffness is found in hypertensive and heart failure suffers [6,7,9–11]. Specifically, healthy aged subjects have been found to have aortic stiffness 50% higher relative to subjects in a young and healthy group, while symptomatic hypertensive patients in heart failure have aortic stiffness further increased by approx. 77% relative to the age matched healthy cohort (i.e. by ∼88% relative to the young and healthy group) [11].
Iron Oxide Nanoparticles Are Less Toxic to Endothelial Cells When Coated With Dextran and Polyethylene Glycol
Authors: Yu Miao , Muzykantov Vladimir , Clyne Alisa Morss
Published: July 2013

Iron oxide nanoparticles are of particular interest for drug delivery applications, since they can be targeted to a specific location using a magnetic field. We are interested in delivering drugs to atherosclerotic plaques via these nanoparticles. However, prior to using nanoparticles in vivo, they must be shown as relatively non-toxic to cells. We and others have shown that bare iron oxide nanoparticles are readily taken up by cells, where they catalyze production of highly toxic reactive oxygen species [1]. This oxidative stress disrupts the cell cytoskeleton, alters cell mechanics, and may change other critical cell functions. Iron oxide nanoparticles for in vivo biomedical applications are often coated with a polysaccharide (eg. dextran) or a polymer (eg. polyethylene glycol, PEG). Both the size and the surface coating of the nanoparticle play an important role in cell toxicity.
A Modular System to Examine Fibroblastic Differentiation of Mesenchymal Stem Cells Under Tensile Loading in Response to Changes in the Extracellular Environment
Authors: Temenoff Johnna S.
Published: July 2013

Hundreds of thousands of injuries to ligaments, tendons or the joint capsule occur in the U.S. each year, resulting in significant reduction of quality of life for many patients [1]. Existing reconstruction techniques for torn tendons/ligaments result in significant morbidity and cannot fully recapitulate the native joint biomechanics, leading to secondary degeneration over time, such as premature osteoarthritis. Thus, tissue-engineered alternatives to current grafts, potentially using stem cells in combination with an appropriate scaffold, are greatly needed. In response, our laboratory is investigating a novel hydrogel system and a custom tensile bioreactor as an in-vitro model to study the formation of both fibrous (ligament) tissue and the ligament-bone interface. In these studies, we examine the effect of tensile loading and the degradability of the surrounding environment on cellular morphology and tendon/ligament extracellular matrix (ECM) production by mesenchymal stem cells (MSCs). In particular, the response of MSCs embedded within hydrogels with varying degrees of susceptibility to degradation by collagenase is explored. In addition, proof-of-principle experiments are presented to extend this system to examine the effect of co-culture of multiple cell types on differentiation of MSCs in a milieu that mimics the bone-ligament insertion.
Computational Study of Unsteady Viscous Flow in Flexible Vessels
Authors: Peet Yulia V. , Chopp David L. , Davis Stephen H. , Miksis Michael J.
Published: July 2013

In this paper, we investigate unsteady behavior of flexible vessels carrying a blood flow. Membrane model with constant tension for the vessel walls and incompressible newtonian fluid approximation for blood is adopted. Developed computational model is applied to simulate the coupled fluid-wall behavior in 2D collapsible channels and 3D collapsible tubes.
Smooth Muscle Cell Orientation on Non-Uniform Stretch Environments
Authors: Richardson William J. , Moore James E.
Published: July 2013

Cells of the artery can respond to mechanical cues in a variety of ways including proliferation, migration, protein secretion, phenotype modulation, and orientation [4, 6]. Many of these responses are related to the progression of disease such as atherosclerosis, emphasizing a need to understand how mechanical signals are translated into biological behaviors. Much work has been done to isolate the effects of particular mechanical inputs on particular cellular responses with rather simple mechanical environments, e.g. uniaxial or uniform equibiaxial stretching. Such experiments have greatly improved our knowledge of mechanobiology, yet many questions regarding these cell responses remain unaddressed; in particular, the effect of non-uniform stretch environments.
Simulation of the Emergence of the Endochondral Ossification Process in Evolution
Authors: Khayyeri Hanifeh , Prendergast Patrick J.
Published: July 2013

The ability of tissues to adapt to the mechanical environment is a remarkable feature of the skeleton. Although the mechano-regulation process is very complex, several mechano-regulation theories for musculo-skeletal tissues have successfully predicted the tissue differentiation and remodelling process in various scenarios with reasonable accuracy (1,2); but how did mechano-regulated bone differentiation emerge in evolution? Early vertebrates, like cartilaginous fishes, could modulate their tissues to the mechanical environment and it is likely that evolution worked with the regulatory genes for skeletal tissues, rather than changes in structural genes, i.e. adapting skeletal tissues to the local conditions rather than involving major changes in cells or tissue types (3).
A Model of the Canine Stifle Joint With Representation of Medial Meniscus During Squat Motion
Authors: Stylianou Antonis , Guess Trent , Olcott Leo , Paiva Gavin , Kia Mohammad , Cook James
Published: July 2013

Subject specific anatomical models of the canine stifle can be extremely valuable in understanding the biomechanical risks and causes associated with cranial cruciate ligament and meniscal injuries. Such models would also be powerful in improving preventative and therapeutic strategies for canines [1]. The menisci play an important role in joint function by transmitting tibio-femoral loads and by reducing the pressure on the articular cartilage. Multibody modeling methods often ignore the menisci in order to simplify the representation of the joint structures.
Computational Model of Microbubble Flows During the Reopening of Airways
Authors: Chen Xiaodong , Ghadiali Samir
Published: July 2013

The acute respiratory distress syndrome (ARDS) is a devastating lung disease in which bacterial infections cause disruption of the blood-gas barrier, flooding and occlusion of pulmonary airways. Patients with ARDS must be placed on a mechanical ventilator to survive. Unfortunately, these ventilators also exacerbate the existing lung injury and as a result the mortality for ARDS is high (∼30–40%). Experimental studies [1,2,3] indicate that the hydrodynamic forces generated during microbubble flows can cause cell death, further barrier disruption and the up-regulation of inflammatory cascades.
Mathematical Simulation and Parametric Study of Flow of a Microbicidal Gel Between Elastic Boundaries
Authors: Karri Sunil , Kieweg Sarah L.
Published: July 2013

Topical microbicides, the next generation prevention tool for HIV and other sexually transmitted pathogens, hold great promise if the target vaginal or rectal epithelium is coated effectively. A microbicide consists of an active ingredient within a polymeric delivery vehicle (e.g. polymeric liquid or ‘gel’). Most research in the field of microbicides has been limited to the development of an active ingredient and many microbicidal trails have failed in the past. Thus, there is a need to design a delivery vehicle that optimizes the efficacy of a microbicidal agent. The effectiveness of the gel depends on the gel’s rheological properties as well as the vaginal tissue properties, vaginal geometry, and external forces like gravity. A good design must take these factors in to consideration and a better understanding of the gel’s flow behavior over the epithelium is important before proceeding with clinical trials.
Elastic Stress Singularities: Implications for the Attachment of Tendon to Bone
Authors: Liu Yanxin , Birman Victor , Chen Chanqing , Thomopoulos Stavros , Genin Guy M.
Published: July 2013

The material mismatch at the attachment of tendon to bone is amongst the most severe for any tensile connection in nature. This is related to the large difference between the stiffness of tendon and bone, whose moduli of elasticity vary by two orders of magnitude. Predictably, such an abrupt change in the stiffness realized over a very narrow insertion site results in high local stresses. One of the implications of the stress distribution is a potential for stress singularities at the junction of the insertion to the bone.
Biomechanical and Microstructural Analysis of Wildtype (C57BL6) Mouse Aorta
Authors: Haskett Darren , Johnson Greg , Azhar Mohamad , Vande Geest Jonathan
Published: July 2013

It is generally accepted that the formation of an aneurysm in the infrarenal aorta is a complex and multi-factorial disease, however little is known about how biomechanical factors may play a role in the progression of aneurysmal disease. Although it is known that human aneurysmal tissue is remodeled in the disease process [1] and that such reorganization leads to altered function [2], the underlying mechanisms by which such changes remains an important unanswered question in the literature. The purpose of this study is to develop a means for determining the biomechanical alterations that occur within the aorta to better understand aneurysmal disease progression.
The Effect of Pulse Pressure on Arterial Wall Permeability and Stiffness
Authors: Hayman Danika M. , Lindsey Merry L. , Han Hai-Chao
Published: July 2013

Artery pulse pressure has been increasingly studied as a factor that can predict overall health. In people younger than 50 the mean pressure tends to increase with age while the pulse pressure remains constant; however, in patients older than 50 the systolic pressure continues to increase while the diastolic pressure starts to decrease resulting in a widened pulse pressure [1]. Stiffening of the artery wall and changes in the ejection fraction from the heart both alter the pulse pressure. Decreases in pulse pressure can also be caused by disease, but mostly this change is caused by the use of steady flow left ventricular assist devices or cardio pulmonary bypass machines [2]. These changes in pulse pressure affect the flow of blood throughout the body and can have effects on the function of organs outside of the cardiovascular system. However the immediate effects of these changes in pulse pressure are not well understood. This study examines the changes in the mechanical properties of the artery wall, arterial permeability and protein levels that occur immediately after a change in pulse pressure.
Changes in Biomechanical Environment of Cardiac Cells in Chick Embryos After Cardiac Outflow Tract Banding
Authors: Liu Aiping , Thornburg Kent , Wang Ruikang , Rugonyi Sandra
Published: July 2013

Embryonic cardiac cells are constantly exposed to biomechanical environments including cyclic stretch and wall shear stress (WSS), which regulate behaviors of cardiac cells, critical to heart development and function [1]. Disturbances in biomechanical environment may contribute to the heart defects that affect 1% of newborns each year in US. However, changes in the biomechanical signals that affect heart development remain undescribed, partly due to a lack of methodology to quantify the biomechanical environment in the embryonic heart.
The Use of Ultrasound Elastography to Assess Regional Variations in Tendon Strain
Authors: Chernak Laura , Thelen Darryl G.
Published: July 2013

Muscle-tendon loading patterns are complex, with computational models suggesting that both muscle and tendinous tissues undergo highly nonuniform deformation patterns [1]. Hence, musculoskeletal tissue injuries may alter both the morphology and mechanical interactions of muscle and tendon, potentially contributing to secondary pathologies. For example, the presence of residual scar tissue following acute strain injury likely alters force transmission across the muscle-tendon junction and contributes to re-injury risk [2]. While visual ultrasonic methods for assessing tendon strain have provided insight into overall tissue mechanics [3], no prior technique has demonstrated the ability to measure strain distributions in vivo. The purpose of the current study was to evaluate the potential use of ultrasound elastography as a tool for measuring in vivo tendon strain patterns. We achieved this purpose by first developing and assessing an elastography-based approach in an ex vivo experimental setup, and then repeating the analysis on pilot ultrasonic data collected in vivo.
Robotic Simulation of an Eccentric Lever Arm Protocol and a Novel Head Weight Protocol for Evaluation of the Subaxial Cervical Spine: An In Vitro Biomechancial Comparison
Authors: Wido Daniel M. , DiAngelo Denis J. , Kelly Brian P.
Published: July 2013

In vitro testing provides a critical tool for understanding the biomechanics of the subaxial cervical spine. Previous common testing protocols used to evaluate the subaxial cervical spine include pure moment, follower load, and eccentric lever arm (EL) loading methods [1,2,3]. Although these methods are widely accepted, there is always a goal to try to better simulate physiologic loading conditions. While the follower load attempts to simulate compression due to muscle activation, no previous protocol has taken into account the constant vertical force vector applied to C2 produced by the weight of the human head. Furthermore, we are unaware of previous direct protocol to protocol comparisons using the same testing platform and test specimens. Our multi-axis programmable robotic testing platform (Spine Robot) provides the means to explore such comparisons. The objectives of this study were: 1) to develop a novel head weight influenced loading protocol (HWL), 2) simulate and compare the EL protocol and the HWL protocol on a single programmable robotic testing frame with a consistent specimen sample group.
Three-Dimensional Characterization of Lumbar Lordosis in Torsion
Authors: Alland J. A. , Espinoza Orías A. A. , An H. S. , Andersson G. B. J. , Inoue N.
Published: July 2013

The curvature of the lumbar spine has been extensively studied, mostly in relation to scoliosis.1 Previous three-dimensional models of scoliosis allowed for the characterization of specific abnormalities in the sagittal, coronal and axial planes. Recent research has shown that these same spinal structure abnormalities (including facet joint orientation) may also be associated with spondylolisthesis,2 aging, and the onset of lower back pain, among other potential etiologies.3 Newer imaging technologies allow for more precise determination of the spinal curvature4 with all of these studies typically carried out in the neutral position (standing or supine). To the best of the author’s knowledge, there is no study of the behavior of the spinal curvature with axial torsion in vivo. We hypothesized that the spinal curvature when experiencing torsion will deviate significantly from the neutral position due to the complex coupled motions in the spine. The objective of this study is to characterize in vivo the change in lumbar segmental lordosis of the asymptomatic spine during torsion.
Quantitative Measurements of Pressure Dependent Laminar Cribrosa Microstructure in Human Eyes
Authors: Yan Dongmei , Keyes Joseph T. , Vande Geest Jonathan P.
Published: July 2013

The lamina cribrosa (LC) is the porous and collagenous tissue where damage to nerve fibers occurs in glaucoma [1]. Bellezza, et al., using a destructive histomorphological technique, studied the deformation of the LC under various intraocular pressures (IOP) in normal and early experimental glaucomatous monkey eyes, and demonstrated that the LC deformed in the early stage of glaucoma [2]. Sigal, et al. conducted computational studies to show that laminar cribrosa presented greatest strains under the effect of elevated IOPs [3]. However, nondestructive quantitative measurements of the microstructural and morphological changes in LC have not yet been extensively reported. The purpose of this study was to develop a protocol to quantify the microstructural changes in the LC, specifically identifying changes in porosity and fiber angle under various IOPs.
Customization of the Fontan Y-Graft: Are Unequal Branches Necessary for Optimal Hepatic Flow Distribution?
Authors: Yang Weiguang , Feinstein Jeffrey A. , Vignon-Clementel Irene E. , Shadden Shawn C. , Marsden Alison L.
Published: July 2013

Due to surgical complexity and clinical complications, single ventricle defects are among the most severe and challenging congenital heart diseases to treat. Patients usually undergo a three-staged surgery. The first stage consists of shunt insertion and aortic reconstruction in a Norwood procedure. In the second stage, the Bidirectional Glenn procedure, the superior vena cava (SVC) is disconnected from the heart and redirected into the pulmonary arteries (PA’s). In the third and final stage, the Fontan procedure, the inferior vena cava (IVC) is connected to the PA’s via a straight Gore-Tex tube, forming a T-shaped junction with or without offset.
A Multiscale Model of Cell Adhesion and Migration on Extracellular Matrices of Defined Stiffness and Adhesivity
Authors: Pathak Amit , Kumar Sanjay
Published: July 2013

Eukaryotic cells actively respond to variations in ligand density and stiffness of their extracellular matrix (ECM). This cell-ECM relationship plays an important role in regulating cell migration, wound healing, tumor invasion and metastasis. A better understanding of these mechanosenstive responses requires more rigorous models of the relationships between ECM biophysical properties, mechanotransductive signals, assembly of contractile and adhesive structures, and cell migration.
A Coupled Computational Framework for Multiscale Modeling and Optimization of Single Ventricle Repair
Authors: Marsden Alison L. , Moghadam Mahdi Esmaily , Yang Weiguang , Baretta Alessia , Corsini Chiara , Vignon-Clementel Irene , Migliavacca Francesco , Feinstein Jeffrey , Hsia Tain-Yen
Published: July 2013

Multiscale modeling provides a means to relate global response to local changes in geometry and hemodynamics in the circulatory system. In this work, we couple a customized lumped parameter network (LPN) representing the whole circulation (heart, systemic and pulmonary circulations) to three-dimensional finite element models of two stages of the single ventricle surgical pathway. A fully-coupled closed-loop approach is employed using custom codes with Neumann boundary conditions at the inlets and outlets. The methodology is described, and applied to two stages of single ventricle repair to illustrate its utility: the BT-shunt (stage 1), and the Fontan surgery (stage 3).
Viscoelastic Properties of Aorta From Oscillatory Pressure Tests
Authors: Romanov Vasily , Agah Mobin Rastgar , Darvish Kurosh
Published: July 2013

Aorta is the largest and most important artery in the body due to its role in conveying all of the oxygenated blood to smaller branches and ultimately to all of the organs in the body. Knowing its mechanical characteristics and material properties is a basic stage in almost all studies on aorta e.g. evaluating the effect of aging and disease, design and manufacturing of compatible stents and traumatic aortic rupture. Since blood vessels are non-homogeneous, non-linear viscoelastic materials and can experience large deformations, a unique formulation that can describe their mechanical behavior under various loading conditions has not been developed yet. Several previous studies looked into modeling of the blood vessels at large deformation, but the models developed did not include the time dependency of the material [1,2]. In this work, we characterized the material properties of aorta under biaxial oscillatory loading at large deformations taking into account its time dependency. A viscoelastic model was developed to describe the relationship between the inflation and pressure.