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Tissue Engineering

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Full-Text Articles in Biomedical Engineering and Bioengineering

Manipulation And Patterning Of Mammalian Cells Using Vibrations And Acoustic Forces, Joel Cooper Apr 2020

Manipulation And Patterning Of Mammalian Cells Using Vibrations And Acoustic Forces, Joel Cooper

Graduate Theses and Dissertations

Recently, there has been a surge in researchers and scientists investigating different methods which move, manipulate, and pattern biological cells. Multiple different mechanisms can be used for cellular manipulation, microfluidics, biochemical queues, and even optics, just to name a few. However, all techniques have their downsides. A majority of these methods require expensive equipment or reagents and can only manipulate a small number of cells at a time.

Some of the most common cell manipulation devices utilize acoustic pressure waves to move the cells to desired locations. Currently, it is unknown what level of force from these types of devices ...


Fluid Delivery System For A Cell Culture On A Microfluidic Chip, Austin J. Roeder, Colleen A. Richards, Emily A. Matteson Mar 2019

Fluid Delivery System For A Cell Culture On A Microfluidic Chip, Austin J. Roeder, Colleen A. Richards, Emily A. Matteson

Biomedical Engineering

This project report provides a description of the progress made in the development of a fluid delivery system for a microfluidic cell culture on a chip. The system is intended to be used in a humidified incubator in a university laboratory and the fluid delivery system is required to exist and operate within that incubator for extended periods of time. Therefore, the system will be gravity-driven and contain no electronic components. The key specification of the system is to provide fluid flow at a constant velocity.

After manufacturing and testing the device, all specifications were met except for the fluid ...


Engineering The Alveolar Gas Exchange Barrier With Extracellular Matrix Coatings For Bioengineered Lungs, Bethany M. Young Jan 2019

Engineering The Alveolar Gas Exchange Barrier With Extracellular Matrix Coatings For Bioengineered Lungs, Bethany M. Young

Theses and Dissertations

Lower respiratory diseases are currently the third leading cause of death worldwide. For many end-stage patients with these diseases, there is no cure and a shortage of donor organs available for transplant. A promising solution is to design regenerative scaffolds or complete bioengineered lungs, using decellularized lung tissues as a template for regeneration. Recent advances in the field have made significant strides towards developing a transplantable lung. However, the current technology has not produced a functional lung for in vivo transplant due to immature gas exchange barriers. The mechanisms driving alveolar barrier maturation and role that extracellular matrix (ECM) plays ...


Chemically Modified Monolayer Surfaces Influence Valvular Interstitial Cell Attachment And Differentiation For Heart Valve Tissue Engineering, Matthew N. Rush Dec 2018

Chemically Modified Monolayer Surfaces Influence Valvular Interstitial Cell Attachment And Differentiation For Heart Valve Tissue Engineering, Matthew N. Rush

Nanoscience and Microsystems ETDs

As a cell mediated-process, valvular heart disease (VHD) results in significant morbidity and mortality world-wide. In the US alone, valvular heart disease VHD is estimated to affect 2.5% of the population with a disproportionate impact on an increasing elderly populous. It is well understood that the primary driver for valvular calcification is the differentiation of valvular interstitial cells (VICs) into an osteoblastic-like phenotype. However, the factors leading to the onset of osteoblastic-like VICs (obVICs) and resulting calcification are not fully understood and a more complete characterization of VIC differentiation and phenotypic change is required before treatment of valve disease ...


Determinants Of Multi-Scale Patterning In Growth Plate Cartilage, Alek Erickson May 2018

Determinants Of Multi-Scale Patterning In Growth Plate Cartilage, Alek Erickson

Theses & Dissertations

ABSTRACT

Functional architectures of complex adaptive systems emerge by dynamic control over properties of individual components. During skeletal development, growth plate cartilage matches bone geometries to body plan requisites by spatiotemporally regulating chondrocyte actions. Bone growth potential is managed by the proximodistal patterning of chondrocyte populations into differentiation zones, while growth vectors are specified by the unique columnar arrangement of clonal groups. Chondrocyte organization at both tissue and cell levels is influenced by a cartilage-wide communication network that relies on zone-specific release and interpretation of paracrine signals. Despite genetic characterization of signaling interactions necessary for cartilage maturation, the regulatory mechanisms ...


Three-Dimensional Endothelial Spheroid-Based Investigation Of Pressure-Sensitive Sprout Formation, Min Song Jan 2016

Three-Dimensional Endothelial Spheroid-Based Investigation Of Pressure-Sensitive Sprout Formation, Min Song

Theses and Dissertations--Biomedical Engineering

This study explored hydrostatic pressure as a mechanobiological parameter to control in vitro endothelial cell tubulogenesis in 3-D hydrogels as a model microvascular tissue engineering approach. For this purpose, the present investigation used an endothelial spheroid model, which we believe is an adaptable microvascularization strategy for many tissue engineering construct designs. We also aimed to identify the operating magnitudes and exposure times for hydrostatic pressure-sensitive sprout formation as well as verify the involvement of VEGFR-3 signaling. For this purpose, we used a custom-designed pressure system and a 3-D endothelial cell spheroid model of sprouting tubulogenesis. We report that an exposure ...


Oxygen Transport, Shear Stress, And Metabolism In Perfused Hepatocyte-Seeded Scaffolds With Radial Pore Architecture: Experimental And Computational Analyses, Chijioke Mbanu Jan 2016

Oxygen Transport, Shear Stress, And Metabolism In Perfused Hepatocyte-Seeded Scaffolds With Radial Pore Architecture: Experimental And Computational Analyses, Chijioke Mbanu

Wayne State University Dissertations

Several modalities have been proposed as treatments or temporary stop-gap for patients suffering from liver failure until a suitable organ is available. However there is still an urgent need for an off-the-shelf device that can accommodate clinically relevant cell numbers, be cultured at physiological oxygen tensions and, can be fully integrated into and heal the injured hepatic space. In this study we investigated the effects that convective and direct oxygenation had on hepatocyte functionality, morphology and viability while cultured in bulk 3D chitosan scaffolds and perfusion bioreactor systems. Cylindrical chitosan scaffolds with radial directed pore structures were fabricated by a ...


Generation And Function Of Glucose-Responsive Insulin Producing Cells Derived From Human Induced Pluripotent Stem Cells, Gohar Shahwar Manzar Aug 2015

Generation And Function Of Glucose-Responsive Insulin Producing Cells Derived From Human Induced Pluripotent Stem Cells, Gohar Shahwar Manzar

Theses and Dissertations

Type I diabetes (T1D) is caused by autoimmune destruction of pancreatic β-cells. Immediate consequences of T1D are severe weight loss, ketoacidosis and death unless insulin is administered. The long-term consequences of T1D are dysregulation of metabolism leading to cardiovascular complications, neuropathy and kidney insufficiency. It is estimated that 3 million Americans have T1D, and its prevalence among young individuals is progressively rising. Islet transplantation is the most effective way to treat T1D. Unfortunately, there is a chronic shortage of cadaveric organ donors to treat all of the patients on the waiting list. Thus, an alternative source of insulin producing cells ...


Articular Cartilage Tissue Engineering Using Chondrogenic Progenitor Cell Homing And 3d Bioprinting, Yin Yu May 2015

Articular Cartilage Tissue Engineering Using Chondrogenic Progenitor Cell Homing And 3d Bioprinting, Yin Yu

Theses and Dissertations

Articular cartilage damage associated with joint trauma seldom heals and often leads to osteoarthritis (OA). Current treatment often fails to regenerated functional cartilage close to native tissue. We previously identified a migratory chondrogenic progenitor cell (CPC) population that responded chemotactically to cell death and rapidly repopulated the injured cartilage matrix, which suggested their potential for cartilage repair. To test that potential we filled experimental full thickness chondral defects with an acellular hydrogel containing SDF-1α. We expect that SDF-1α can increase the recruitment of CPCs, and then promote the formation of a functional cartilage matrix with chondrogenic factors. Full-thickness bovine chondral ...


Polysaccharide-Based Shear Thinning Hydrogels For Three-Dimensional Cell Culture, Vasudha Surampudi Jan 2015

Polysaccharide-Based Shear Thinning Hydrogels For Three-Dimensional Cell Culture, Vasudha Surampudi

Theses and Dissertations

The recreation of the complicated tissue microenvironment is essential to reduce the gap between in vitro and in vivo research. Polysaccharide-based hydrogels form excellent scaffolds to allow for three-dimensional cell culture owing to the favorable properties such as capability to absorb large amount of water when immersed in biological fluids, ability to form “smart hydrogels” by being shear-thinning and thixotropic, and eliciting minimum immunological response from the host. In this study, the biodegradable shear-thinning polysaccharide, gellan-gum based hydrogel was investigated for the conditions and concentrations in which it can be applied for the adhesion, propagation and assembly of different mammalian ...


Amphiphilic Degradable Polymer/Hydroxyapatite Composites As Smart Bone Tissue Engineering Scaffolds: A Dissertation, Artem B. Kutikov Nov 2014

Amphiphilic Degradable Polymer/Hydroxyapatite Composites As Smart Bone Tissue Engineering Scaffolds: A Dissertation, Artem B. Kutikov

GSBS Dissertations and Theses

Over 600,000 bone-grafting operations are performed each year in the United States. The majority of the bone used for these surgeries comes from autografts that are limited in quantity or allografts with high failure rates. Current synthetic bone grafting materials have poor mechanical properties, handling characteristics, and bioactivity. The goal of this dissertation was to develop a clinically translatable bone tissue engineering scaffold with improved handling characteristics, bioactivity, and smart delivery modalities. We hypothesized that this could be achieved through the rational selection of Food and Drug Administration (FDA) approved materials that blend favorably with hydroxyapatite (HA), the principle ...


Humidity Effect On The Structure Of Electrospun Core-Shell Pcl-Peg Fibers For Tissue Regeneration Applications, Adam P. Golin Apr 2014

Humidity Effect On The Structure Of Electrospun Core-Shell Pcl-Peg Fibers For Tissue Regeneration Applications, Adam P. Golin

Electronic Thesis and Dissertation Repository

With the aim of creating a biodegradable scaffold for tympanic membrane (TM) tissue regeneration, core-shell nanofibers composed of a poly(caprolactone) shell and a poly(ethylene glycol) core were created using a coaxial electrospinning technique. In order to create fibers with an optimal core-shell morphology, the effect of relative humidity (RH) on the core-shell nanofibers was systematically studied, with a FITC-BSA complex encapsulated in the core to act as a model protein. The core-shell nanofibers were electrospun at relative humidity values of 20, 25, 30, and 40% RH within a glove box outfitted for humidity control. The core-shell morphology of ...


Design Of Controlled Environment For Tissue Engineering, Malcolm Gerald Lapera Feb 2014

Design Of Controlled Environment For Tissue Engineering, Malcolm Gerald Lapera

Master's Theses

Design of Controlled Environment for Tissue Engineering

Malcolm Lapera

Tissue engineering aims at relieving the need for donor tissue and organs by developing a process of creating viable tissues in the laboratory setting. With over 120,000 people awaiting a transplant, the need for generating tissue engineered organs is very large [3]. In order for organs to be engineered, a few issues need to be overcome. A work space that both creates an environment which maintains cell viability over an extended period of time as well as accommodates the necessary fabrication equipment will be needed to further tissue engineering research ...


Human Hair Keratin Protein, Hair Fibers And Hydroxyapatite (Ha) Composite Scaffold For Bone Tissue Regeneration, Samuel Siyum Jan 2014

Human Hair Keratin Protein, Hair Fibers And Hydroxyapatite (Ha) Composite Scaffold For Bone Tissue Regeneration, Samuel Siyum

ETD Archive

The field of tissue engineering aims at promoting the regeneration of tissues or replacement of failing or malfunctioning tissue by means of combining a scaffold material, adequate cells and bioactive molecules. Different materials have been proposed for use as three-dimensional porous scaffolds for bone tissue engineering procedures. Among them, polymers of natural origin are one of the most attractive options mainly due to their similarities with the extracellular matrix (ECM), chemical versatility as well as typically good biological performance. In this study, two biocompatible composite scaffolds were developed from natural polymer by tissue engineering approach and tested in vitro. The ...


Investigating The Reproducibility Of The Current Bvm Protocol, Corey Gross Mar 2013

Investigating The Reproducibility Of The Current Bvm Protocol, Corey Gross

Biomedical Engineering

Coronary Artery Disease (CAD) is responsible for 1 death every minute in the US. Angioplasty with the implantation of stents is a common treatment method for CAD. Although there is a variety of stents currently on the market, there is still a need to develop new types for different pathologic conditions. Preliminary assessment of the physiological response to new stents is needed as they are being developed. The FDA approval process implemented today is a long, tedious path with a range of testing methods that include static in vitro testing and high-cost animal testing. Tissue engineered blood vessels have been ...


Nanomechanics Of Electrospun Nanofibres For Tissue Engineering Of The Tympanic Membrane, Sara Makaremi Dec 2012

Nanomechanics Of Electrospun Nanofibres For Tissue Engineering Of The Tympanic Membrane, Sara Makaremi

Electronic Thesis and Dissertation Repository

The Tympanic Membrane (TM), also known as the eardrum, includes layers of organized collagen nanofibres which play an essential role in sound transmission. Perforations that are caused by infection or accident must be repaired in order to restore hearing. Tympanoplasty is performed using grafts that are prepared from bladder, cartilage, temporal fascia and cadaveric skin. However, since mechanical properties of these grafts do not match those of the original TM, normal hearing is not fully restored. The goal of this study is to develop nanofibrous scaffolds for tissue engineering of the TM in order to circumvent the complications addressed with ...


Integrated Fiber Electrospinning: Creating Spatially Complex Electrospun Scaffolds With Minimal Delamination, Casey Grey Aug 2012

Integrated Fiber Electrospinning: Creating Spatially Complex Electrospun Scaffolds With Minimal Delamination, Casey Grey

Theses and Dissertations

Tissue engineering scaffolds come in many shapes and sizes, however, due to difficulty manufacturing the microstructure architecture required in tissue engineering, most scaffolds are architecturally non-dynamic in nature. Because the microstructural architecture of all biological tissues is inherently complicated, non-dynamic tissue engineering scaffolds tend to be a poor platform for tissue regeneration. The current method for manufacturing dynamic tissue engineering scaffolds involves electrospinning successive layers of different fibers, an approach that exhibits no fiber transition between layers and subsequent delamination problems. In this study we aim to address the design challenges of tissue engineering scaffolds through our novel integrated fiber ...


Preparation And Characterization Of A Self-Crimp Side-By-Side Bicomponent Electrospun Material, Yang Han Aug 2012

Preparation And Characterization Of A Self-Crimp Side-By-Side Bicomponent Electrospun Material, Yang Han

Theses and Dissertations

Bicomponent composite fibers have been widely used in the textile industry and are gaining increasing attention on biomedical applications. In this research, polycaprolactone/poly (lactic acid) side-by-side bicomponent fibers were created for the application of a biodegradable scaffold. The side-by-side structure endowed the fiber with self-crimps when it was processed under certain conditions. This material was produced by electrospinning and collected on a high speed rotating mandrel to get highly oriented fibers. A mechanical stretch at the same direction was done followed by a wet heat treatment for polymer retraction. Crimped fibers were demonstrated by scanning electron microscopy. The quantitative ...


Mechanical Activation Of Valvular Interstitial Cell Phenotype: A Dissertation, Angela M. Throm Quinlan Aug 2012

Mechanical Activation Of Valvular Interstitial Cell Phenotype: A Dissertation, Angela M. Throm Quinlan

GSBS Dissertations and Theses

During heart valve remodeling, and in many disease states, valvular interstitial cells (VICs) shift to an activated myofibroblast phenotype which is characterized by enhanced synthetic and contractile activity. Pronounced alpha smooth muscle actin (αSMA)-containing stress fibers, the hallmark of activated myofibroblasts, are also observed when VICs are placed under tension due to altered mechanical loading in vivo or during in vitro culture on stiff substrates or under high mechanical loads and in the presence of transforming growth factor-beta1 (TGF-β1). The work presented herein describes three distinct model systems for application of controlled mechanical environment to VICs cultured in vitro ...


Development And Characterization Of An In- House Custom Bioreactor For The Cultivation Of A Tissue Engineered Blood-Brain Barrier, Amin Hadi Mirzaaghaeian Jul 2012

Development And Characterization Of An In- House Custom Bioreactor For The Cultivation Of A Tissue Engineered Blood-Brain Barrier, Amin Hadi Mirzaaghaeian

Master's Theses

The development of treatments for neurological disorders such as Alzheimer’s and Parkinson’s disease begins by understanding what these diseases affect and the consequences of further manifestation. One particular region where these diseases can produce substantial problems is the blood-brain barrier (BBB). The BBB is the selective diffusion barrier between the circulating blood and the brain. The barrier’s main function is to maintain CNS homeostasis and protect the brain from the extracellular environment. The progression of BBB research has advanced to the point where many have modeled the BBB in vitro with aims of further characterizing and testing ...


Tissue Engineering A Blood Vessel Mimic While Monitoring Contamination Through Sterility Assurance Testing, Navid Djassemi Jul 2012

Tissue Engineering A Blood Vessel Mimic While Monitoring Contamination Through Sterility Assurance Testing, Navid Djassemi

Master's Theses

Tissue Engineering A Blood Vessel Mimic While Monitoring Contamination Through Sterility Assurance Testing

Navid Djassemi

Tissue engineering blood vessel mimics has been proposed as a method to analyze the endothelial cell response to intravascular devices that are used in today’s clinical settings for the treatment of cardiovascular disease. Thus, the development of in vitro blood vessel mimics (BVMs) in Cal Poly’s Tissue Engineering Lab has introduced the possibility of assessing the characteristics of cellular response to past, present, and future intravascular devices that aim at treating coronary artery disease.

This thesis aimed at improving the methods and procedures ...


Development And Characterization Of Plga And Eptfe Blood Vessel Mimics Using Gene Expression Analysis, Michael Gibbons, Sarah Ur Jun 2012

Development And Characterization Of Plga And Eptfe Blood Vessel Mimics Using Gene Expression Analysis, Michael Gibbons, Sarah Ur

Biomedical Engineering

Tissue engineered blood vessels (TEBV’s) have the potential to act not only as a replacement for diseased vessels, but also as a testing platform for intravascular devices such as stents. To this end, the goal of this study was to develop protocols for the construction of TEBV’s composed of human vascular cells and either expanded polytetrafluoroethylene (ePTFE) or poly-lactic-co-glycolic acid (PLGA), as well as a protocol for gene expression in those TEBV’s. Initial experiments involved only human umbilical vein endothelial cells (HUVEC’s), but after low cell confluency and spreading in single-sodded vessels a second cell type ...


In Vivo Immunotoxicological Evaluation Of Electrospun Polycaprolactone (Epcl) And Investigation Of Epcl As A Drug Delivery System For Immunomodulatory Compounds, Colleen Mcloughlin May 2012

In Vivo Immunotoxicological Evaluation Of Electrospun Polycaprolactone (Epcl) And Investigation Of Epcl As A Drug Delivery System For Immunomodulatory Compounds, Colleen Mcloughlin

Theses and Dissertations

Electrospun materials have potential use in many biomedical applications such as soft tissue replacements or as scaffolds to target drug delivery to local sites. Electrospinning is a polymer processing technique that can be used to create materials composed of fibers with diameters ranging from the micron to the nanoscale. We investigated the effects of microfibrous and nanofibrous electrospun polycaprolactone (EPCL) on innate, cell-mediated, and humoral components of the immune system. Results demonstrated that in both young (12 week) and old (6 month) mice, EPCL had no effect on various immune parameters. With its lack of immunotoxicity, EPCL presents an excellent ...


Effects Of Different Microenvironmental Conditions On The Growth And Differentiation Of Dental Pulp Stem Cells, Matthew Cupelli May 2012

Effects Of Different Microenvironmental Conditions On The Growth And Differentiation Of Dental Pulp Stem Cells, Matthew Cupelli

All Theses

Human teeth are very complex structures that are susceptible to many different pathologies due to poor dental health. Currently, there are many restorative methods to reestablish some of the function that teeth have, but the materials used in these methods all have drawbacks and cannot fully mimic the native teeth. Tissue engineering research groups have begun to explore regenerating bone or dental tissue using mesenchymal stem cells derived from the bone marrow. However, our group focuses on regenerating dental tissues using multipotent stem cells from dental pulp.
Dental pulp stem cells (DPSCs) have shown similarities to bone marrow stem cells ...


Dynamic Endothelialization Of Aortic Heart Valve Scaffolds, Richard Pascal Jan 2012

Dynamic Endothelialization Of Aortic Heart Valve Scaffolds, Richard Pascal

All Theses

Cardiovascular disease is the number one killer worldwide affecting both the heart and blood vessels. Valvular heart disease can arise from calcification, and structural deterioration resulting in a stenotic or regurgitant valve incapable of proper function. With approximately 275,000 valve replacements performed annually worldwide, the need for replacement heart valves is well established. Currently, treatment of valvular heart disease is limited to two options (mechanical and bioprosthetic). Both replacement valves have their own drawbacks, which have driven research in the bioengineering field to focus on the development of a tissue engineered heart valve (TEHV) capable of growth and self-repair ...


Silk Fibroin-Based Scaffolds For Tissue Engineering Applications, Jennifer Mccool Jul 2011

Silk Fibroin-Based Scaffolds For Tissue Engineering Applications, Jennifer Mccool

Theses and Dissertations

This study focused on the comparison of the electrospun silk scaffolds to the electrospun silk fibroin gel scaffolds. Moreover, this study examined the differences in cross-linking effects of genipin and methanol as well as solvents on the mechanical properties and cell compatibility of the scaffolds. Silk scaffolds were electrospun from an aqueous solution or 1,1,1,3,3-hexafluoro-2-propanol (HFIP) without genipin, immediately after 8 % (wt) genipin was added to the solution, and 18 hours after genipin blended with the solution. Uniaxial tensile testing determined that the silk scaffolds electrospun from water exhibit a higher modulus and peak stress than ...


Characterization And Implementation Of A Decellularized Porcine Vessel As A Biologic Scaffold For A Blood Vessel Mimic, Aubrey N. Smith Jun 2011

Characterization And Implementation Of A Decellularized Porcine Vessel As A Biologic Scaffold For A Blood Vessel Mimic, Aubrey N. Smith

Master's Theses

Every 34 seconds, someone in the United States suffers from a heart attack. Most heart attacks are caused by atherosclerotic build up in the coronary arteries, occluding normal blood flow. Balloon angioplasty procedures in combination with a metal stent often result in successful restoration of normal blood flow. However, bare metal stents often lead to restenosis and other complications. To compensate for this problem, industry has created drug-eluting stents to promote healing of the artery wall post stenting. These stents are continually advancing toward better drug-eluting designs and methods, resulting in a need for fast and reliable pre-clinical testing modalities ...


An Investigation Of Process Parameters To Optimize The Fiber Diameter Of Electrospun Vascular Scaffolds Through Experimental Design, Steffi Wong Dec 2010

An Investigation Of Process Parameters To Optimize The Fiber Diameter Of Electrospun Vascular Scaffolds Through Experimental Design, Steffi Wong

Biomedical Engineering

No abstract provided.


Cell-Mediated Elastic Matrix Regeneration Toward Regression Of Abdominal Aortic Aneurysms, Carmen Gacchina Jun 2010

Cell-Mediated Elastic Matrix Regeneration Toward Regression Of Abdominal Aortic Aneurysms, Carmen Gacchina

All Dissertations

Abdominal aortic aneurysms (AAAs) are typically fusiform (symmetric) dilations of the aortic wall most commonly arising below the renal arteries. The progression is typically associated with an activated smooth muscle cell (SMC) phenotype, diminished density of mature medial elastic fibers, and an elevated presence of matrix-degrading enzymes (e.g., matrix-metalloproteases; MMPs), which may ultimately lead to vessel rupture. Currently, no surgical or non-surgical methods are available to regress AAAs via regeneration of new elastin matrices to regain normal vessel contour, particularly due to the inherently poor elastin synthesis by adult vascular cells and absence of methods to stimulate the same ...


Regulation Of Angiogenesis By Adhesive And Mechanical Cues From The Extracellular Matrix, Colette Shen May 2010

Regulation Of Angiogenesis By Adhesive And Mechanical Cues From The Extracellular Matrix, Colette Shen

Publicly Accessible Penn Dissertations

Angiogenesis, the sprouting of new capillaries from existing blood vessels, is essential for the survival of tissues and normally occurs during development and wound healing. Successful vascularization of engineered tissues is currently a major challenge, as it is critical for the survival and incorporation of implanted tissue replacements. While the role of soluble factors in regulating angiogenesis is well established, there is significant interest in uncovering the contributions of cellular interactions with the extracellular matrix (ECM). We chose to study the role of cell-ECM adhesion in regulating angiogenesis, with the hypothesis that quantitative changes in the degree of cell-ECM adhesion ...