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Full-Text Articles in Engineering

Spark Plasma Sintering Of Low Modulus Titanium-Niobium-Tantalum-Zirconium (Tntz) Alloy For Biomedical Applications, Nicholas Mavros, Taban Larimian, Javier Esqivel, Rajeev Kumar Gupta, Rodrigo Contieri, Tushar Borkar Dec 2019

Spark Plasma Sintering Of Low Modulus Titanium-Niobium-Tantalum-Zirconium (Tntz) Alloy For Biomedical Applications, Nicholas Mavros, Taban Larimian, Javier Esqivel, Rajeev Kumar Gupta, Rodrigo Contieri, Tushar Borkar

Mechanical Engineering Faculty Publications

In metallurgy, titanium has been a staple for biomedical purposes. Its slow toxicity and alloying versatility make it an attractive choice for medical applications. However, studies have shown the difference in elastic modulus between titanium alloys (116 GPa) and human bone (10–40 GPa), which contributes to long term issues with loose hardware fixation. Additionally, long term studies have shown elements such as vanadium and aluminum, which are commonly used in Ti-6Al-4V biomedical alloys, have been linked to neurodegenerative diseases like Alzheimer and Parkinson. Alternative metals known to be less toxic are being explored as replacements for alloying elements in ...


Three-Dimensional Human Neural Stem Cell Culture For High-Throughput Assessment Of Developmental Neurotoxicity, Pranav Joshi Jan 2019

Three-Dimensional Human Neural Stem Cell Culture For High-Throughput Assessment Of Developmental Neurotoxicity, Pranav Joshi

ETD Archive

Only a few hundred of compounds, among tens of thousands of commercially available compounds, have been tested for developmental neurotoxicity (DNT) due to the limitations of current guidelines for DNT which are based entirely on in vivo experiments. In vivo studies are highly expensive and time-consuming, which often do not correlate to human outcomes. There is a key gap in our ability to predict in vivo outcomes accurately and robustly using in vitro assays. This is particularly the case for predicting the toxicity of chemicals on the developing human brains. Conventional in vitro assays are typically performed in two-dimensional (2D ...


Thenar Muscle And Transverse Carpal Ligament Relationship, Jeremy Granieri Loss Jan 2019

Thenar Muscle And Transverse Carpal Ligament Relationship, Jeremy Granieri Loss

ETD Archive

The transverse carpal ligament (TCL) acts as a partial origin for the thenar muscles (abductor pollicis brevis (APB), flexor pollicis brevis (FPB), opponens pollicis (OPP)). The attachment between the thenar muscles and TCL implies a relationship between the tissues. The thenar muscles rely on their origins for thumb motion and force production. However, individual thenar origin information is lacking. Further information regarding the anatomical relationship between the individual thenar muscles and TCL may provide insight into thenar muscle function. In addition, the TCL responds to thenar muscle contraction as shown by volar migration of the TCL during various thumb movements ...


Compensation For Inertial And Gravity Effects In A Moving Force Platform, Sandra K. Hnat, Ben J.H. Van Basten, Antonie J. Van Den Bogert Jun 2018

Compensation For Inertial And Gravity Effects In A Moving Force Platform, Sandra K. Hnat, Ben J.H. Van Basten, Antonie J. Van Den Bogert

Mechanical Engineering Faculty Publications

Force plates for human movement analysis provide accurate measurements when mounted rigidly on an inertial reference frame. Large measurement errors occur, however, when the force plate is accelerated, or tilted relative to gravity. This prohibits the use of force plates in human perturbation studies with controlled surface movements, or in conditions where the foundation is moving or not sufficiently rigid. Here we present a linear model to predict the inertial and gravitational artifacts using accelerometer signals. The model is first calibrated with data collected from random movements of the unloaded system and then used to compensate for the errors in ...


The Effect Of Cognitive Limb Embodiment On Vascular Physiological Response, Hala Elsir Mustafa Osman Jan 2018

The Effect Of Cognitive Limb Embodiment On Vascular Physiological Response, Hala Elsir Mustafa Osman

ETD Archive

The rubber hand illusion (RHI) is a visual-tactile perceptual illusion commonly used to study body ownership. In this paradigm, a rubber hand is positioned in front of a participant, and the person’s real hand is hidden from sight behind a barrier. When the real hand and the rubber hand are stroked synchronously, individuals perceive the rubber hand as if it were their own; it becomes “embodied.” This illusory experience of body ownership is associated with multimodal integration of touch and vision. From these visual-tactile-cognitive mechanisms, we establish that our hands belong to us when what we see matches what ...


Advanced Manufacturing Of Titanium Alloys For Biomedical Applications, Nicholas C. Mavros Jan 2018

Advanced Manufacturing Of Titanium Alloys For Biomedical Applications, Nicholas C. Mavros

ETD Archive

In metallurgy, Titanium has been a staple for biomedical purposes. Its low toxicity and alloying versatility make it an attractive choice for medical applications. However, studies have shown the difference in elastic modulus between Titanium alloys (116 GPa) and human bone (40-60 GPa) contribute to long term issues with loose hardware fixation. Additionally, long term studies have shown elements such as Vanadium and Aluminum, which are commonly used in Ti-6Al-4V biomedical alloys, have been linked to neurodegenerative diseases like Alzheimers and Parkinsons. Alternative metals known to be less toxic are being explored as replacements for alloying elements in Titanium alloys ...


Characterizing The Effects Of High-Intensity Exercise On Balance And Gait Under Dual-Task Conditions In Parkinson’S Disease, El Iva Baron Jan 2018

Characterizing The Effects Of High-Intensity Exercise On Balance And Gait Under Dual-Task Conditions In Parkinson’S Disease, El Iva Baron

ETD Archive

Parkinson’s disease (PD) is a neurodegenerative disorder, characterized by four cardinal motor symptoms including bradykinesia, tremor, rigidity, and postural instability, and non-motor symptoms including cognitive impairment. Daily activities, such as walking and maintaining balance, are impacted due to impairments in motor function, and are further exacerbated with the addition of cognitive loading, or dual-tasking (DT). High-intensity exercise has demonstrated centrally-mediated improvements of PD symptoms, with additional positive effects on overall health. The goal of this project was to identify changes in dynamic balance recovery and gait function under conditions with and without increased cognitive load after a high-intensity exercise ...


Neuromuscular Reflex Control For Prostheses And Exoskeletons, Sandra K. Hnat Jan 2018

Neuromuscular Reflex Control For Prostheses And Exoskeletons, Sandra K. Hnat

ETD Archive

Recent powered lower-limb prosthetic and orthotic (P/O) devices aim to restore legged mobility for persons with an amputation or spinal cord injury. Though various control strategies have been proposed for these devices, specifically finite-state impedance controllers, natural gait mechanics are not usually achieved. The goal of this project was to invent a biologically-inspired controller for powered P/O devices. We hypothesize that a more muscle-like actuation system, including spinal reflexes and vestibular feedback, can achieve able-bodied walking and also respond to outside perturbations. The outputs of the Virtual Muscle Reflex (VMR) controller are joint torque commands, sent to the ...


Feasibility Of Using An Equilibrium Point Strategy To Control Reaching Movements Of Paralyzed Arms With Functional Electrical Stimulation, Matthew Huffman Jan 2018

Feasibility Of Using An Equilibrium Point Strategy To Control Reaching Movements Of Paralyzed Arms With Functional Electrical Stimulation, Matthew Huffman

ETD Archive

Functional electrical stimulation (FES) is a technology capable of improving the quality of life for those with the loss of limb movement related to spinal cord injuries. Individuals with high-level tetraplegia, in particular, have lost all movement capabilities below the neck. FES has shown promise in bypassing spinal cord damage by sending electrical impulses directly to a nerve or muscle to trigger a desired function. Despite advancements in FES, full-arm reaching motions have not been achieved, leaving patients unable to perform fundamental tasks such as eating and grooming. To overcome the inability in current FES models to achieve multi-joint coordination ...


A Synthesis Platform For Temperature Responsive Star Polymers, Schmitt J. Richard Jr. Jan 2018

A Synthesis Platform For Temperature Responsive Star Polymers, Schmitt J. Richard Jr.

ETD Archive

Star polymers are a class of branched polymers comprised of several polymer chains extending from a central point. Star polymers have applications in biopharmaceuticals where they have been proposed to be suitable drug delivery vehicles. Star polymers have traditionally been synthesized through chemical synthesis with added functionality provided by grafting on the arms. This complex synthesis can be simplified by using a biosynthetic approach which enables precise control of molecular weight and composition. This approach is demonstrated using star polymers with arms composed of a temperature responsive protein-based polymer termed elastin-like polypeptide (ELP). Star polymers are characterized based on the ...


Stabilization Of Hypoxia Inducible Factor By Cobalt Chloride Can Alter Renal Transepithelial, Subhra Sankar Nag Jan 2018

Stabilization Of Hypoxia Inducible Factor By Cobalt Chloride Can Alter Renal Transepithelial, Subhra Sankar Nag

ETD Archive

Kidney cyst expansion, stagnant fluid accumulation, and insufficient vascular supply can result in localized chronic ischemia-hypoxia in kidney cysts, as well as in normal renal epithelia adjacent to a cyst. We hypothesize that in normal epithelia near a cyst, the stabilization of Hypoxia Inducible Factor 1a (HIF1a), a major regulator of cellular response to hypoxia, can cause altered paracellular and transcellular transport, transforming a normal absorptive phenotype to a secretory and paracellularly leaky phenotype, leading to cyst expansion. Using 100 µmol/L cobalt chloride (CoCl2), HIF1a was stabilized in cellular nucleus of a mouse cortical collecting duct cell line (mCCD ...


Predictive Simulations Of Gait And Their Application In Prosthesis Design, Anne D. Koelewijin Jan 2018

Predictive Simulations Of Gait And Their Application In Prosthesis Design, Anne D. Koelewijin

ETD Archive

Predictive simulations predict human gait by solving a trajectory optimization problem by minimizing energy expenditure. These simulations could predict the effect of a prosthesis on gait before its use. This dissertation has four aims, to show the application of predictive simulations in prosthesis design and to improve the quality of predictive simulations. Aim 1 was to explain joint moment asymmetry in the knee and hip in gait of persons with a transtibial amputation (TTA gait). Predictive simulations showed that an asymmetric gait required less effort. However, a small effort increase yielded a gait with increased joint moment symmetry and reduced ...


High-Throughput Metabolism-Induced Toxicity Assays On A 384-Pillar Plate, Sooyeion Kang Jan 2018

High-Throughput Metabolism-Induced Toxicity Assays On A 384-Pillar Plate, Sooyeion Kang

ETD Archive

The U.S Environmental Protection Agency (EPA) launched the Transform Tox Testing Challenge in 2016 with the goal of developing practical methods that can be integrated into conventional high-throughput screening (HTS) assays to better predict the toxicity of parent compounds and their metabolites in vivo. In response to this need and to retrofit existing HTS assays for assessing metabolism-induced toxicity of compounds, we have developed a 384-pillar plate that is complementary to traditional 384-well plates and ideally suited for culturing human cells in three dimensions (3D) at a microscale. Briefly, human embryonic kidney (HEK) 293 cells in a mixture of ...


Modeling Liver Diseases Using Hepatic Cell Microarrays, Alexander David Roth Jan 2018

Modeling Liver Diseases Using Hepatic Cell Microarrays, Alexander David Roth

ETD Archive

Hepatocellular carcinoma (HCC) is an invasive and aggressive cancer of the liver that arises due to chronic cirrhosis. Research into understanding HCC has focused on two-dimensional (2D) and three-dimensional (3D) technologies to simulate the liver microenvironment and use animal models to model how HCC affects the rest of the body. 3D hydrogel models are desired because they can mimic the transport behavior observed in vivo by structurally mimicking the extracellular matrix (ECM) without the ethical concerns of animal models. However, hydrogels can be toxic to cells and require optimal procedures for appropriate handling. In this study, we created 3D models ...


Surface Functionalization Of Pure-Chirality Carbon Nanotubes By Covalent And Noncovalent Chemistry, Fjorela Xhyliu, Niyousha Mohammad Shafie Jan 2018

Surface Functionalization Of Pure-Chirality Carbon Nanotubes By Covalent And Noncovalent Chemistry, Fjorela Xhyliu, Niyousha Mohammad Shafie

Undergraduate Research Posters 2018

Single-wall carbon nanotubes (SWCNTs) are one-dimensional cylindrical nanostructures with distinct electronic and optical properties. With all its atoms on the surface, SWCNTs have been widely explored for chemical modification through noncovalent and covalent chemistry, which can provide promising applications in bioimaging and sensing. Here we investigated surface functionalization of purechirality SWCNTs with various glycopolymers, surfactants, and RPMI cell culture media with and without fetal bovine serum (FBS). Raman, vis-NIR absorption, and vis-NIR fluorescence spectra of SWCNTs in various solvent environments were monitored over time. While nanotube aggregation was not observed for incubation in FBS containing RPMI for 8 hours, interactions ...


Treatment Of Non-Epithelial Vaginal Cells From Lysyl Oxidase Like One Knockout Mice (Loxl 1) With Nanoparticles (Nps), Priya Patel Jan 2018

Treatment Of Non-Epithelial Vaginal Cells From Lysyl Oxidase Like One Knockout Mice (Loxl 1) With Nanoparticles (Nps), Priya Patel

Undergraduate Research Posters 2018

Female pelvic floor dysfunction includes pelvic organ prolapse (POP) due to multiple vaginal births causing elastin strength to be reduced. Several normal functions are compromised including bladder control, fecal continence, and painful urination and many other symptoms. Currently no effective treatment is known and women seek surgical mesh implants to correct these issues which are not entirely safe nor effective. The condition of POP affects women across the world and effective treatment is sought. Varying proteins including lysyl oxidase (LOX), tissue inhibitors of metalloproteinases, and matrix metalloproteinases are involved in elastin homeostasis. In this experiment, non-epithelial vaginal cells (NEVCs) retrieved ...


Multi-Phase Waste Gasification – Reaction Engineering For Sustainable Living Environments, Kristen M. Reyes, Mason J. Lang Jan 2018

Multi-Phase Waste Gasification – Reaction Engineering For Sustainable Living Environments, Kristen M. Reyes, Mason J. Lang

Undergraduate Research Posters 2018

Gasification converts carbon-based (organic) materials into gaseous products typically referred to as synthetic gas. This technology is an alternative for reducing carbon footprint of energy generation as well as for waste management. This research examines Catalytic Gasification as a route to Sustainability while converting spaceflight and municipal waste into high-value products. As polyethylene (PE) makes up one of the largest portions of both municipal and space waste, this project centered its attention on the gasification of mid-density PE. We used a slurry containing middensity PE, water, and solid catalysts (ruthenium on alumina, Ru/Al2O3) in a 1:1 PE/Ru ...


The Role Of Synthesis Solvent In Particle Size Of Metal Organic Frameworks, Jonathan Krisak Jan 2018

The Role Of Synthesis Solvent In Particle Size Of Metal Organic Frameworks, Jonathan Krisak

Undergraduate Research Posters 2018

Metal organic frameworks are a class of nanoporous materials with pore sizes ranging from 0.5 to 3 nm and high surface areas (500-6000 m2/g). These materials have potential applications in industrial catalysis, separation and purification, bio-mimetics, drug delivery, semiconductors, sensors and other electronics. The aim of this study is to understand the role of solvent in control of the particle size of the final MOF product. CuBTC MOF has been used as a model MOF in this study to understand this effect. Altering the dielectric constant of solvents is a potential method of controlling the particle size. The ...


Boundary Effects On The Locomotion Of Active Janus Particles, Marola W. Issa, Nicky R. Baumgartner Jan 2018

Boundary Effects On The Locomotion Of Active Janus Particles, Marola W. Issa, Nicky R. Baumgartner

Undergraduate Research Posters 2018

Self-propelled or “active” micrometer scale particles are capable of supplying local mechanical work, necessary for microscale cargo delivery and useful in other applications within bioimaging and sensing. Research in the last decade has focused on developing, measuring, and manipulating the locomotion mechanisms of active particles in simple environments. However, many applications will be in complex environments with nearby boundaries or variations in physiochemical cues. This poster reports the directed motion of platinum coated polystyrene particles at infinite dilution in the presence of H2O2, which acts as a fuel to drive motion. A transport mechanism called “diffusiophoresis” drives motion of the ...


Prediction Of Metabolism-Induced Neurotoxicity On A 384pillarplate, Rushabh Patel, Pranav Joshi, Soo-Yeon Kang, Stephen Hong, Parnian Bigdelou Jan 2018

Prediction Of Metabolism-Induced Neurotoxicity On A 384pillarplate, Rushabh Patel, Pranav Joshi, Soo-Yeon Kang, Stephen Hong, Parnian Bigdelou

Undergraduate Research Posters 2018

Metabolism of compounds including neurotoxins primarily occurs in the liver by a variety of drug-metabolizing enzymes (DMEs) followed by a series of downstream responses. Unmodified (or parent) neurotoxins are transported into human hepatocytes through several influx transporters or via passive diffusion and undergo Phase I and Phase II biotransformation by DMEs before they are cleared. Neurotoxins and their metabolites generated from human hepatocytes could potentially lead to the toxic effects on neural stem cells (NSCs) as the reactive metabolites have potential for producing reactive oxygen species (ROS), which can lead to irreversible oxidative damage to NSCs via lipid peroxidation, DNA ...


A 3d Cancer Cell Migration Assay On A 384-Pillar Plate With Sidewalls, Nicholas Lesh, Alexander Roth, Stephen Hong, Oju Jeon, Eben Alsberg Jan 2018

A 3d Cancer Cell Migration Assay On A 384-Pillar Plate With Sidewalls, Nicholas Lesh, Alexander Roth, Stephen Hong, Oju Jeon, Eben Alsberg

Undergraduate Research Posters 2018

Hepatocellular carcinoma (HCC) is an aggressive liver cancer where prognosis is heavily tied to metastasis progression. Researchers look to determine the triggers for metastasis to control its spread. The goal of this project is to determine these triggers by quantifying Hep3B cell migration on a high-throughput platform. We infected Hep3B cells with lentiviruses containing mCherry to produce stable fluorescent cells. Next, we determined the stability of growth factors in oxidized, methacrylated alginate (OMA) hydrogel by binding growth factors with methacrylated heparin sulfate (MHS) before encapsulating in OMA, printing onto the 384-pillar plate with sidewalls, and quantifying growth factor release via ...


Dendrite Morphology Of Pb-5.8 Sb Alloy: Gradient Freeze Ds With Cross-Section Area Change, Michael Shannon Jan 2018

Dendrite Morphology Of Pb-5.8 Sb Alloy: Gradient Freeze Ds With Cross-Section Area Change, Michael Shannon

Undergraduate Research Posters 2018

Directional solidification (DS) is the process of solidifying a metal alloy from one end to another resulting in aligned primary dendrites which are branched tree like features. Alignment of primary dendrites along [100] direction and their uniformity and distribution along the DS length determines the mechanical properties. These properties are especially important for single crystal turbine blade applications in modern gas turbine engines. Convection during solidification plays an important role in formation of detrimental defects, such as, misaligned grains, non-uniformity of dendrites and composition inhomogeneity. In this study the microstructural evolution during “Gradient Freeze DS process”, involving an abrupt cross-section ...


Characterizing Complexes Of Dna And Elastin-Like Polypeptides, Bryce Noe Jan 2018

Characterizing Complexes Of Dna And Elastin-Like Polypeptides, Bryce Noe

Undergraduate Research Posters 2018

Elastin-like polypeptides (ELPs) are a class of environmental responsive materials. When prepared with a protein motif that selectively binds to nucleic acids, a nucleic acid-ELP complex can be formed, conferring the responsive properties of ELP onto the nucleic acid. One possible use for such a complex is in DNA origami, where nanoscaled assemblies of DNA can be transformed into nanomachines by using the ELP as an actuator. Other possible uses include the isolation and extraction of a selected strands of genetic material, or the delivery of genetic material to a cell. Using a bacterial expression system, our lab has prepared ...


Methodology Development For The Implementation Ofmicrofluidic Mixers, Tahir Butt, Gautam Mahajan Jan 2018

Methodology Development For The Implementation Ofmicrofluidic Mixers, Tahir Butt, Gautam Mahajan

Undergraduate Research Posters 2018

Microfluidic platforms have been widely regarded as defining technologies for the development of chemical and biological synthesis and analysis systems, due to benefits associated with reduced reactant consumption, increases by orders of magnitude of the surface-to-volume ratios, and greatly enhanced control over reactions variables such as temperature and pressure. However, one of the bottlenecks for their wide application is the difficulty in achieving mixing, given the typical laminar flows in these systems. In this work we implement experimentally, various strategies using geometrical features to control the fluid motion and induce stirring flows. The mixers are fabricated using soft-lithography in PDMS ...


Implementation Of A Reverse Staggered-Herringbone Microfluidic Mixer For High-Throughput Polymeric Nanoparticles Synthesis, Alexa Roberts Jan 2018

Implementation Of A Reverse Staggered-Herringbone Microfluidic Mixer For High-Throughput Polymeric Nanoparticles Synthesis, Alexa Roberts

Undergraduate Research Posters 2018

The goal of this research is to implement and optimize the operating conditions of a microfluidic mixer to synthesize polymeric nanoparticles (NPs) in a high-throughput fashion. Using a reverse staggered-herringbone microfluidic mixer that we recently designed, the effects of experimental conditions such as flowrate and reactant composition on NP characteristics were investigated and optimized. The device design allowed for physical contact between two streams of fluids – one containing poly(lactic-co-glycolic acid; PLGA) in acetonitrile and the other deionized water, to allow for efficient mixing and NP precipitation to occur. The resulting NPs were characterized using dynamic light scattering (DLS) and ...


Idiosyncratic Drug-Induced Liver Injury (Idili): Potential Mechanisms And Predictive Assays, Alexander D. Roth, Moo-Yeal Lee Jan 2017

Idiosyncratic Drug-Induced Liver Injury (Idili): Potential Mechanisms And Predictive Assays, Alexander D. Roth, Moo-Yeal Lee

Chemical & Biomedical Engineering Faculty Publications

Idiosyncratic drug-induced liver injury (IDILI) is a significant source of drug recall and acute liver failure (ALF) in the United States. While current drug development processes emphasize general toxicity and drug metabolizing enzyme- (DME-) mediated toxicity, it has been challenging to develop comprehensive models for assessing complete idiosyncratic potential. In this review, we describe the enzymes and proteins that contain polymorphisms believed to contribute to IDILI, including ones that affect phase I and phase II metabolism, antioxidant enzymes, drug transporters, inflammation, and human leukocyte antigen (HLA). We then describe the various assays that have been developed to detect individual reactions ...


Design And Control Of A Powered Rowing Machine With Programmable Impedance, Jose Humberto De La Casas Zolezzi Jan 2017

Design And Control Of A Powered Rowing Machine With Programmable Impedance, Jose Humberto De La Casas Zolezzi

ETD Archive

Due to the rise of obesity, diabetes and cardiovascular disease, research in human performance and physical activity has received increased attention. Rowing machines are used for performance improvements through concentric exercises, however a combination of concentric and eccentric actions is known to improve the effectiveness of training. In this work, a conventional rowing machine was modified to include an electric motor and a robust impedance control system, enabling programmable impedance with concentric and eccentric capabilities. Eccentric exercises are known to contribute significantly to the efficacy of training and to diminish the detrimental effects of humans operating in microgravity for long ...


C-Jun N-Terminal Kinase Inhibitory Nanotherapeutics For Regenerative Elastic Matrix Repair In Abdominal Aortic Aneurysms, Andrew T. Camardo Jan 2017

C-Jun N-Terminal Kinase Inhibitory Nanotherapeutics For Regenerative Elastic Matrix Repair In Abdominal Aortic Aneurysms, Andrew T. Camardo

ETD Archive

Abdominal aortic aneurysms (AAA) are localized expansions of the aorta wall that continue to grow until they reach a critical size and fatally rupture. This growth is driven by the chronic disruption, degradation, and subsequent loss of aortal wall elastic fibers by matrix metalloproteinases (MMPs) secreted by inflammatory cells recruited to the aorta wall following an injury stimulus, and the inherent inability of vascular smooth muscle cells (SMCs) to naturally repair or regenerate elastic fibers. This leads to a net loss of elastic matrix and the continuing weakening of the aortal wall until eventual rupture. Current treatments seek to reinforce ...


Cathepsin K Targeting Matrix Regenerative Nanoparticles For Small Abdominal Aortic Aneurysm Repair, Jonathan M. Fox Jan 2017

Cathepsin K Targeting Matrix Regenerative Nanoparticles For Small Abdominal Aortic Aneurysm Repair, Jonathan M. Fox

ETD Archive

Abdominal aortic aneurysms (AAAs) are characterized by the loss of elasticity in the aorta wall leading to a chronic increase in diameter and resulting in rupture. This is due to the lack of regeneration of elastic fibers and chronic proteolytic breakdown of elastic fibers within the aorta mediated by matrix metalloproteinases (MMPs), specifically MMP-2 and -9. Previous studies in our lab have shown cationic amphiphile-surface functionalized poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) loaded with doxycycline (DOX) to inhibit MMP activity and stimulate elastic matrix synthesis, effects we attributed to both low doses (< 10 mg/ml) of DOX released and independent effects of cationic amphiphile pendant groups on the NP surface. This promises application of these NPs to arrest or regress AAA growth since high oral DOX dosing inhibits new elastic matrix formation in the AAA wall and has undesirable side effects. In this study, we investigated feasibility of antibody-based active targeting of intravenously infused NPs to the AAA wall. Cathepsin K, a cysteine protease, is a biomarker for AAA and overexpressed in abdominal aortic aneurysm tissue making it an ideal target moiety. We have shown using a covalent conjugation method of modifying the surface of the NPs with a cathepsin K antibody resulted in a more robust antibody attachment which did not affect the DOX release profile. Cathepsin K expression was confirmed to be localized on the cell surface and utilizing cathepsin K Ab-conjugated NPs, we demonstrated an increased NP localization to the cathepsin K overexpressing cells in vitro and ex vivo. Importantly, the DOX-loaded NPs demonstrated pro-elastogenic and anti-proteolytic effects in aneurysmal smooth muscle cells supporting their use as regenerative therapies to arrest and regress AAA growth. Preliminary data has been collected indicating cathepsin K Ab-conjugated NP targeting to AAAs in elastase-injured rat models. The study outcomes support the feasibility of using cathepsin K Ab-conjugated NPs as a targeted therapy for elastic matrix regeneration in AAA tissue and will serve as a basis for already initiated follow up studies to assess NP biodistribution, in situ retention in the AAA wall, and safety as a function of time.


Going Green: Experimental Adaptation Of Scenedesmus Dimorphus To Marine Conditions, Mohammed Khalil Jan 2017

Going Green: Experimental Adaptation Of Scenedesmus Dimorphus To Marine Conditions, Mohammed Khalil

Undergraduate Research Posters 2017

Algae has gained some interest as the need for alternative fuels becomes more pressing. Reliance on fossil fuels is causing our environment and economy harm, and is not sustainable moving forward. Lipid rich algae strains can be used in the production of biofuels, and provide an alternative fuel source. One challenge facing the prospect of algae as a fuel source is that lipid rich algae grows exclusively in freshwater. Considering the scarcity and cost to use freshwater for algae growth, interest has grown in the possibility of adapting lipid rich, freshwater algae to a seawater environment. Seawater can have up ...