Engineering Commons^™

Targeted Mesenchymal Stem Cell Differentiation From Induced Pluripotent Stem Cells For Therapeutic Application, Tackla Winston

Dissertations - ALL

Over the past decade, mesenchymal stem cells have increasingly gained interest as a cell source for the treatment of a variety of diseases. This is because they play several roles in tissue homeostasis and regeneration, such as altering the immune response to limit inflammation, aiding tissue repair through the release of various proteins, cytokines and growth factors, or differentiating into functional cells in specific tissues. The interest in MSCs for biomanufacturing applications has resulted in the development of various protocols to differentiate them from pluripotent sources. These protocols, however, fail to account for the differences that exist between MSCs from …

Leveraging Isocyanate Chemistry For Low Cost And Highly Functional Hydrogels, Henry Beaman

Dissertations - ALL

The development of novel biomaterials is an important step in providing higher quality products for wound healing, drug delivery, and tissue engineering. Progress is consistently being made in the development of new polymers, yet new polymer systems are often expensive and/or involve complex multistep synthesis methods. These limitations could hinder the translation and scalability of functionalized materials. To address the issues of complex synthesis and high cost, we have devised strategies for polymeric modification using isocyanate chemistry. Isocyanates are used in the manufacturing of polyurethanes. Isocyanates are highly reactive with common functional groups, such as amines, hydroxyls, and carboxylic acids. …

Engineering Temporal And Spatial Complexity In Biomaterial Scaffolds For Cardiac Disease Modeling And Mechanobiology, Chenyan Wang

Dissertations - ALL

Temporal and spatial mechanical cues play an important role in heart development, function, and disease manifestation. A deeper understanding of cardiac mechanobiology is especially important for fundamental biology and clinical diagnosis or heart disease treatment. Currently, human induced pluripotent stem cells (hiPSCs) are widely used to build human cell or tissue models, but culturing them in a petri dish fail to recapitulate the mechanical complexity in the native heart. To create a mechanical environment with better pathophysiological relevance, biomaterial scaffolds are usually employed to mimic the mechanical cues originated from extracellular matrix (ECM) remodeling. The goal of this dissertation is …

Advanced In Vitro Models For Studying Bone Physiology, Kairui Zhang

Dissertations - ALL

Bone is a highly calcified organic-inorganic composite tissue with complicated hierarchical structure. The presence of complex multi-cellular organization within opaque mineralized matrix makes it challenging to use conventional methods to study in vivo bone physiology even using model animals. To address this challenge, numerous in vitro models have been developed to study bone physiology under well-defined and repeatable experimental conditions although proving their physiological relevance remains a key challenge. This work aims to design and develop new in vitro models that better represent in vivo bone physiology with defined control over chemical and physical microenvironments, at low costs and high …

Fabrication Of Polymeric Microparticles Loaded With Zoledronic Acid To Treat Osteoarthritis, Yohely Maria Espiritusanto

Theses - ALL

Osteoarthritis (OA), a disease caused by wearing and tearing of articular cartilage, affectsover 32.5 million Americans. Synovial inflammation is now recognized as a major contributor to OA progression and pain. Activated synovial macrophages in an OA joint are believed to play a major role in low grade inflammation found in OA. Bisphosphonates such as zoledronic acid (ZA) are known to induce apoptosis specifically in macrophages and several of them are being evaluated as a disease-modifying osteoarthritis drug in clinical trials. However, ZA is rapidly cleared from the joint after systemic or localized direct injection into the joint. In this study …

Effects Of Surface Topography On Macrophages And Bacterial Cells, Joseph Carnicelli

Theses - ALL

An association has been found between the texture of breast implants and anaplastic large cell lymphoma, which led to some textured implants to be withdrawn from the market in 2019. There is evidence that these cancers are associated with the harboring of bacteria on the surfaces of the textured implants. It is possible that specific topographic features hinder the removal of attached bacteria by inhibiting macrophage phagocytosis or promoting biofilm formation. Here we examine how bacteria and macrophages interact with recessive surface topographies as analogs to the surfaces seen on textured breast implants. Changes in bacteria morphology were observed among …

Shape Memory Polymer Foaming With Tunable Interconnectivity Using Off-The-Shelf Foaming Components, Natalie Marie Petryk

Theses - ALL

The ability to tune pore structures of gas-blown polyurethane shape memory polymer (SMP) foams easily and safely could improve their outcomes as hemostatic dressings or tissue engineering scaffolds and overall commercialization efforts. Incorporating physical blowing agents into the polymer mix can be used to tune pore size and interconnectivity without altering foam chemistry. Enovate (HFC-254fa) is a commonly used physical blowing agent in gas-blown foams, but the Environmental Protection Agency (EPA) considers its use unacceptable because it is a hydrofluorocarbon that contributes to global warming. Here, off-the-shelf solvents accepted for use by the EPA, acetone, dimethyoxymethane (methylal), and methyl formate, …

Manipulated Electrochemical Surface Reactions Induced By Oscillatory Electric Potentials On Metal Based Electrodes, Thomas Stone Welles

Dissertations - ALL

This research effort investigates the manipulation of surface electrochemical reactions induced by oscillating electric potentials on the surface of metal-based electrodes. Specifically, this research presents experimental data identifying modified electrochemical surface reactions caused by low magnitude electric potential oscillations on multilayered catalytic membranes and on implanted biometallic alloys. The scope of this effort consists of four major components: (1) perform an exhaustive literature review and analysis of the current understanding in applied surface electrochemistry and develop potential theoretical frameworks by which to interpret the experimental results; (2) identify the electrochemical manipulation via electrical oscillation while reacting nitric oxide on a …

Atomistic Investigation Of Nucleosomal H3 Histone Tail In Unmodified And Epigenetically Modified States, Kathryn Piston

Dissertations - ALL

Epigenetics is a growing area of research that could potentially unlock the understanding of questions like how and why we develop certain diseases, how we age, how we inherit certain traits and even how our species evolves. Epi is a prefix meaning above, referring to chemical tags that sit above your genetics and dictate gene expression. Although there are many known links between certain epigenetic tags and diseases like cancer, the molecular mechanisms behind these links remains elusive. Gaining a novel understanding of the behavior of key biological targets for cancer like the histone H3 tail motivated this work. Histone …

Antimicrobial Susceptibility Of P. Aeruginosa Clinical Isolates, Tian Gao

Theses - ALL

Long-term infection caused by P. aeruginosa poses a major threat to personal and public health, and causes billions of dollars in medical expenses. To develop more effective controls, it is important to accurately evaluate antibiotic susceptibility of clinical isolates and understand how susceptibility changes during the course of infection. Conventional drug susceptibility tests using nutrient-rich media have been questioned regarding their relevance due to the difference between the model in vivo test conditions and the environment in the patients. Here, we report that 27 clinical strains of P. aeruginosa isolated from cystic fibrosis patients showed higher drug resistance in Artificial …

A Computational Model For Calcium Signaling In Osteocyte Cell Cultures Under Mechanical Stimulation, Courtney Rose Ogando

Theses - ALL

Bone is a highly complex and organized tissue that is composed of an abundance of cells including the osteocyte. While it is known that osteocytes are responsible for the control of the bone remodeling process and the maintenance of calcium (Ca2+) homeostasis using their network of gap junction connections, their complete role is not yet fully understood. It is also known that various bone related diseases as well as cancer demonstrate an alteration of Ca2+ homeostasis during the progression of the disease. Previous researchers have combined computational modeling with experimental studies to gain a better understanding of cell-to-cell Ca2+ signaling …

Computational Investigation Of Biological Membranes, Allyson Karmazyn

Theses - ALL

Lipids are the building blocks of biological membranes, and the types of lipids that compose these cellular envelopes influence the physicochemical properties of the chemicals that can enter or exit the cell across the membrane. This work focuses on the lipid membrane compositions of eukaryotic (red blood cells) and prokaryotic (Pseudomonas aeruginosa) membranes. By analyzing the lipid-lipid and lipid-protein interactions results of the computational simulations, insights into lipid aggregation, bilayer leaflet behavior, membrane asymmetry, and small molecule transport through protein channels were obtained. The differences between prokaryotic and eukaryotic cell membranes are qualitative known; however, this work provides these concepts …

Optical Printing Of Multiscale Hydrogel Structures, Zheng Xiong

Dissertations - ALL

Hydrogel has been a promising candidate to recapitulate the chemical, physical and mechanical properties of natural extracellular matrix (ECM), and they have been widely used for tissue engineering, lab on a chip and biophotonics applications. A range of optical fabrication technologies such as photolithography, digital projection stereolithography and laser direct writing have been used to shape hydrogels into structurally complex functional devices and constructs. However, it is still greatly challenging for researchers to design and fabricate multiscale hydrogel structures using a single fabrication technology.

To address this challenge, the goal of this work is the design and develop novel multimode …

Computational Algorithms For Predicting Membrane Protein Assembly From Angstrom To Micron Scale, Nandhini Rajagopal

Dissertations - ALL

Biological barriers in the human body are one of the most crucial interfaces perfected through evolution for diverse and unique functions. Of the wide range of barriers, the paracellular protein interfaces of epithelial and endothelial cells called tight junctions with high molecular specificities are vital for homeostasis and to maintain proper health. While the breakdown of these barriers is associated with serious pathological consequences, their intact presence also poses a challenge to effective delivery of therapeutic drugs. Complimenting a rigorous combination of in vitro and in vivo approaches to establishing the fundamental biological construct, in addition to elucidating pathological implications …

Predicting Tight Junction Formation Via Claudin Chimeras, Patrick Matthew Marsch

Theses - ALL

Tight junctions are vital to epithelial and endothelial barrier functions aiding in ion transport and preventing toxins from crossing into paracellular space. Claudins, made of four transmembrane helices and two extracellular loops, are a major part of the assembly of tight junctions along with other transmembrane proteins. The dimer interactions of two members of the 27-known members of the claudin family—claudin-2 and claudin-4—were analyzed. We created claudin chimera by switching claudin 2’s extracellular loops with claudin 4’s. The chimeras were analyzed using molecular dynamic simulations by comparing them to the natural claudins. This analysis provided new insight into the assembly …

Blood-Material Interactions With Degradable Shape Memory Polymer Foams, Ellen Barlow Shepherd

Theses - ALL

Shape memory polymer (SMP) foams are a class of smart materials that show promise for managing uncontrolled hemorrhage on the battlefield. The current standard treatments of gauze and tourniquets are not able to effectively control hemorrhage in up to 80% of combat injuries. Most hemostatic devices also require removal within 12 hours of application. Patient transportation to a facility for removal may not be possible within this time frame and the removal process itself can cause further damage to the wound. As an alternative hemostatic device, polyurethane SMP foams have shown to be effective and biocompatible hemostats; however, removal still …

Computational Algorithms For Predicting Membrane Protein Assembly From Angstrom To Micron Scale, Nandhini Rajagopal

Dissertations - ALL

Biological barriers in the human body are one of the most crucial interfaces perfected through evolution for diverse and unique functions. Of the wide range of barriers, the paracellular protein interfaces of epithelial and endothelial cells called tight junctions with high molecular specificities are vital for homeostasis and to maintain proper health. While the breakdown of these barriers is associated with serious pathological consequences, their intact presence also poses a challenge to effective delivery of therapeutic drugs. Complimenting a rigorous combination of in vitro and in vivo approaches to establishing the fundamental biological construct, in addition to elucidating pathological implications …

Molecular Investigation Of The Intestinal Barrier In Health And Disease, Santita Ebangwese

Honors Capstone Projects - All

The intestinal epithelial barrier contributes to the absorption of nutrients and in maintaining homeostasis. Several intestinal disorders such as Crohn’s disease and Ulcerative Colitis show common pathological features corresponding to a decreased intestinal epithelial barrier function, which makes it imperative to investigate the functional units of the intestinal barriers formed by complex protein interfaces called the tight junctions. Among the diverse set of transmembrane proteins involved in the formation of tight junctions, the mal-distribution of claudin family of proteins show direct correlation to compromised barrier functioning. Interestingly, claudin-3 expression reduces drastically in compromised barriers, while an increased expression of claudin-23 …

Development Of An Inflammatory Joint Fluid Corrosion Assessment Method For Metallic Biomaterials, Kathleen Pieri

Honors Capstone Projects - All

There is currently no systematic way to analyze the corrosion response of orthopedic alloys in contact with human joint fluid. The goal of this project was to design and test a small device that can successfully run electrochemical tests on retrieved inflamed joint fluids. Methods of fluid testing analysis were also explored. The a small electrochemical cell was created using polypropylene for the body and an electrode cartridge that could be disposed of after each test. In total the device could hold 4 mL of liquid. Testes were preformed using titanium, stainless steel, and CoCrMo alloys as the working electrodes …

Investigating The Shelf Life Of Benzoyl Peroxide Coated Nozzles For Bone Cement Application, Alysen Leigh Demzik

Honors Capstone Projects - All

Two-solution bone cements (TSBC) were developed to address the limitations of current powder-liquid bone cements, however are characterized by a limited shelf life due to spontaneous free radical polymerization. As a solution to pre-polymerization concerns, the initiator benzoyl peroxide (BPO) was removed from the cement solution and incorporated into a thin film coating within the static mixing nozzle, allowing the BPO to integrate with the TSBC as it is mixed for use. Only short-term storage of BPO-coated nozzles and the subsequent effects on bone cement properties is known. The goal of this study was to investigate the effects of time, …

A Study Of Ciliary Beating In Chlamydomonas, Xin Li

Honors Capstone Projects - All

The goal of this research is to understand how a unicellular green alga, Chlamydomonas-reinhardtii, responds to red light (670nm) and sound waves, by monitoring the beating frequency of its two cilia, which control cell motility. Ciliary beating frequency (BF) is proportional to the production of ATP, mainly generated by photosynthesis. A photosynthesis inhibitor, 3-(3-, 4-dichlorophenyl)-1, 1-dimethylurea (DCMU) decreases ATP production by photosynthesis. I used DCMU as a tool to analyze the red light effect on BF.

In the process of studying the effect of red light, I unexpectedly discovered experimental conditions for unstable ciliary beating (as shown in the video). …

Raman Spectroscopic Investigation Of Chondroitinase Abc Treatment After Spinal Cord Injury In An Organotypic Model, Shane Ruberto

Theses - ALL

This study investigated (1) the ability of an organotypic model of spinal cord injury (SCI) to recapitulate significant pathobiological events of in vivo SCI from a Raman spectroscopic perspective, and (2) the Raman spectroscopic effects of chondroitinase ABC (cABC) treatment on said model of SCI. Tissue from mouse spinal cords was excised, sectioned, and placed into culture, before being systematically injured to induce trauma. Cultures with and without cABC treatment were assessed using Raman spectroscopy at varying times post-injury. We demonstrate that Raman spectral phenomena characteristic of SCI can be observed using an organotypic model. By comparing these phenomena with …

Polysaccharide-Based Nanocarriers For Improved Drug Delivery, Nan Zhang

Dissertations - ALL

The field of drug delivery has provided a solution to the limited efficacy and high toxicity of many drugs. Nano-sized drug carriers are popular because their size allows for selective accumulation in the diseased area. Polysaccharides are non-toxic and biodegradable natural polymers that can serve as the basis for these nano-sized carriers. Polysialic acid (PSA) is such a polysaccharide with strong hydrophilicity that may reduce uptake by the reticuloendothelial system and prolong drug circulation. In this study, we developed PSA-based nanocarriers, specifically micelles and nanoparticles, for improved drug delivery with improved efficacy and minimized toxicity. PSA-based micelle systems were developed …

Improving Bioactivity And The Anti-Bacterial Properties Of Two-Solution Bone Cement Containing Cross-Linked Polymethylmethacrylate (Pmma) Nanospheres (Η-Tsbc), Shailly Jariwala

Biomedical and Chemical Engineering - Dissertations

The high viscosity standard two-solution bone cements (STSBC) developed in our laboratory exhibits several advantages over other commercial powder-liquid cement formulations. However, the high monomer concentration, viscosity, and exothermal temperature are considered a major limitation to the use of this material. Modified two-solution cements containing cross-linked polymethylmethacrylate (PMMA) nanospheres (η-TSBC), as part of the polymer phase, were fabricated as the first step for optimization of cement viscosity for application of the material in the treatment of vertebral compression fractures using vertebroplasty (VP) and kyphoplasty (KP). The η-TSBC exhibited reduced viscosity, lower polymerization exotherm, and residual monomer in comparison to STSBC. …

Controlling Bacterial Persister Cells With Low Level Electric Currents, Henry Lars Peterson

Honors Capstone Projects - All

Bacterial persister cells present a growing concern as they inherit the ability to tolerate high concentrations of antibiotics and repopulate after an antibiotic treatment leading to chronic diseases. Pseudomonas aeruginosa causes many human infections including skin infections and those associated with burn injuries, and implanted medical devices, and are associated with Cystic Fibrosis. Recently, the Ren Lab developed a novel approach to eliminate persister cells of P. aeruginosa, including those in biofilms, using low level electric currents. To evaluate the safety of this method and to better understand how the underlying elements, this study focused on the cytotoxicity of …

Characterization Of Polyacrylonitrile Carbon Fibers, Christian Burke Iversen

Biomedical and Chemical Engineering – Theses

Carbon fiber composites are a widely used, advanced material with exceedingly high strength to weight properties. In this thesis, a literature overview of carbon fiber manufacturing was provided, as well as a thorough analysis of in- house electrospun polyacrylonitrile fiber stabilization and surface modification of the resulting carbon fibers. In the first section, an overview of precursor fiber fabrication is provided, followed by an analysis of stabilization using surface and bulk composition, dimensional analysis, and functional group analysis via FTIR. The second section uses the current stabilization procedure to develop carbon nanofibers. Fibers first underwent a nitric acid oxidation time …

Voltage Effects On Cells Cultured On Metallic Biomedical Implants, Seyed Morteza Haerihosseini

Biomedical and Chemical Engineering - Dissertations

Electrochemical voltage shifts in metallic biomedical implants occur in-vivo due to a number of processes including mechanically assisted corrosion. Surface potential of biomedical implants and excursions from resting open circuit potential (OCP), which is the voltage they attain while in contact with an electrolyte, can significantly change the interfacial properties of the metallic surfaces and alter the behavior of the surrounding cells, compromising the biocompatibility of metallic implants. Voltages can also be controlled to modulate cell function and fate. To date, the details of the physico-chemical phenomena and the role of different biomaterial parameters involved in the interaction between cells …

Nitric Oxide Releasing Polymers For Vascular Graft Applications, Ifeanyi U. Onyejekwe

Biomedical and Chemical Engineering - Dissertations

Nitric oxide [NO] is an endogenous gas involved in a multitude of physiological functions, ranging from vasodilatation, inflammatory response to inhibition of platelet aggregation. Significant interest exists for therapeutic application of exogenous NO, particularly for the improvement of foreign-body responses of biomaterials. One challenge amongst several others that must be taken into consideration is NO's short half-life, ranging from 2-3 s, in physiological systems. Researchers have worked on synthesizing materials, formally referred to as NO donors/NONOates capable of preserving NO and spontaneous gas release upon contact with blood under physiological conditions. Two groups of these commercially available NO donors known …

The Role Of Fluorescence And Human Factors In Quantitative Transdermal Blood And Tissue Analysis Using Nir Raman Spectroscopy, Bin Deng

Biomedical and Chemical Engineering - Dissertations

This research is part of an ongoing project aimed at the application of combined near infrared (NIR) Raman and fluorescence spectroscopy to noninvasive in vivo blood analysis including but not limited to glucose monitoring. Coping with practicalities of human factors and exploring ways to obtain and use knowledge gained about autofluorescence to improve algorithms for blood and tissue analysis are the general goals of this research. Firstly, the study investigated the various sources of human factors pertinent to our concerns, such as fingerprints, turgor, skin hydration and pigmentation. We then introduced specialized in vivo apparatus including means for precise and …

Design And Implementation Of A Shoulder Simulator, Chelsea Lynn Kowal

Honors Capstone Projects - All

The main objective of this thesis project is to build a shoulder simulator to be able to understand the mechanics of the shoulder, specifically the rotator cuff and deltoid muscles. The shoulder simulator should be able to mimic the important motions of the human shoulder by pulling on tendons of cadaver shoulders and moving the shoulder in various specified motions. In my thesis project, I worked on creating a shoulder simulator that would control the rotator cuff muscles along with the three deltoid muscles. In order to do this, I needed to design and test the shoulder simulator using cadaver …