Biomedical Engineering and Bioengineering Commons^™

Therapeutic Potential Of Catechins And Derivatives For The Prevention Of Alzheimer’S Disease, Shelby Elaine Chastain

Theses and Dissertations

Alzheimer’s disease (AD) is a neurodegenerative condition that affects 1 in 9 people over the age of 65, an estimated 5.4 million Americans. It is the only disease among the top 10 that cannot be prevented, cured, or treated. Based on the lack of a viable therapeutic for the prevention or cure of AD, it is vital that therapeutic research for AD continues. AD is characterized by the deposition of extracellular neuritic plaques comprised of insoluble amyloid-β (Aβ) fibrils. These plaques are formed from the amyloidogenic aggregation of Aβ monomer, generated from the cleavage of the amyloid precursor protein (APP) …

Automated Image Analysis And Spatial Computational Modeling Of Nf-Kb In Cerebrovascular Endothelial Cells, Kasey Catalfomo

Theses and Dissertations

Cerebrovascular endothelial cells play a key part in the inflammatory response of the blood-brain barrier in pathological conditions such as Alzheimer’s disease. Specifically, the NF-κB signaling pathway plays a central role. Better understanding of the factors in inflammatory disease progression can lead to more effective treatments for such devastating illnesses like Alzheimer’s, asthma, arthritis, cancer, diabetes and many more inflammatory diseases. The proposed approach analyzes spatial NF-κB distribution contained in multispectral stacked micrograph images of cerebrovascular endothelial cells indexed based on dose of the activating protein and the length of activation. Image analysis code identifies the location of nuclear boundaries …

Development And Characterization Of Lung Derived Extracellular Matrix Hydrogels, Robert A. Pouliot

Theses and Dissertations

Chronic obstructive pulmonary disease (COPD) including emphysema is a devastating condition, increasing in prevalence in the US and worldwide. There remains no cure for COPD, rather only symptomatic treatments. Due to unique challenges of the lung, translation of therapies for acute lung injury to target chronic lung diseases like COPD has not been successful. We have been investigating lung derived extracellular matrix (ECM) hydrogels as a novel approach for delivery of cellular therapies to the pulmonary system.

During the course of this work we have developed and characterized a lug derived ECM hydrogel that exhibits “injectability,” allowing cells or dugs …

An Injectable Stem Cell Delivery System For Treatment Of Musculoskeletal Defects, Shirae Leslie

Theses and Dissertations

The goal of this research was to develop a system of injectable hydrogels to deliver stem cells to musculoskeletal defects, thereby allowing cells to remain at the treatment site and secrete soluble factors that will facilitate tissue regeneration. First, production parameters for encapsulating cells in microbeads were determined. This involved investigating the effects of osmolytes on alginate microbead properties, and the effects of alginate microbead cell density, alginate microbead density, and effects of osteogenic media on microencapsulated cells. Although cells remained viable in the microbeads, alginate does not readily degrade in vivo for six months. Therefore, a method to incorporate …

The Molecular And Mechanical Mechanisms Of The Age-Associated Increase In The Severity Of Experimental Ventilator Induced Lung Injury, Joseph Ames Herbert

Theses and Dissertations

Abstract

Background

The majority of patients requiring mechanical ventilation are over the age of 65 and advanced age is known to increase the severity of ventilator-induced lung injury (VILI) and mortality. However, the mechanisms which predispose aging ventilator patients to increased mortality rates are not fully understood.

Pulmonary edema is a hallmark of VILI and the severity of edema increases with age. Ventilation with conservative fluid management decreases mortality rates in acute respiratory distress (ARDS) patients, but has not been investigated in VILI. We hypothesized that age-associated increases in pulmonary edema promote age-related increases in ventilator-associated mortality. Endoplasmic reticulum (ER) …

Electrophysiology Of Basal Ganglia (Bg) Circuitry And Dystonia As A Model Of Motor Control Dysfunction, Deepak Kumbhare

Theses and Dissertations

The basal ganglia (BG) is a complex set of heavily interconnected nuclei located in the central part of the brain that receives inputs from the several areas of the cortex and projects via the thalamus back to the prefrontal and motor cortical areas. Despite playing a significant part in multiple brain functions, the physiology of the BG and associated disorders like dystonia remain poorly understood. Dystonia is a devastating condition characterized by ineffective, twisting movements, prolonged co-contractions and contorted postures. Evidences suggest that it occurs due to abnormal discharge patterning in BG-thalamocortocal (BGTC) circuitry. The central purpose of this study …

Novel Small Airway Model Using Electrospun Decellularized Lung Extracellular Matrix, Bethany M. Young

Theses and Dissertations

Chronic respiratory diseases affects many people worldwide with little known about the mechanisms diving the pathology, making it difficult to find a cure. Improving the understanding of smooth muscle and extracellular matrix (ECM) interaction is key to developing a remedy to this leading cause of death. With currently no relevant or controllable in vivo or in vitro model to investigate diseased and normal interactions of small airway components, the development of a physiologically relevant in vitro model with comparable cell attachment, signaling, and organization is necessary to develop new treatments for airway disease. The goal of this study is to …

Improved Capability Of A Computational Foot/Ankle Model Using Artificial Neural Networks, Ruchi D. Chande

Theses and Dissertations

Computational joint models provide insight into the biomechanical function of human joints. Through both deformable and rigid body modeling, the structure-function relationship governing joint behavior is better understood, and subsequently, knowledge regarding normal, diseased, and/or injured function is garnered. Given the utility of these computational models, it is imperative to supply them with appropriate inputs such that model function is representative of true joint function. In these models, Magnetic Resonance Imaging (MRI) or Computerized Tomography (CT) scans and literature inform the bony anatomy and mechanical properties of muscle and ligamentous tissues, respectively. In the case of the latter, literature reports …

Characterization Of Poly(Dimethylsiloxane) Blends And Fabrication Of Soft Micropillar Arrays For Force Detection, Thomas J. Petet Jr

Theses and Dissertations

Diseases involving fibrosis cause tens of thousands of deaths per year in the US alone. These diseases are characterized by a large amount of extracellular matrix, causing stiff abnormal tissues that may not function correctly. To take steps towards curing these diseases, a fundamental understanding of how cells interact with their substrate and how mechanical forces alter signaling pathways is vital. Studying the mechanobiology of cells and the interaction between a cell and its extracellular matrix can help explain the mechanisms behind stem cell differentiation, cell migration, and metastasis. Due to the correlation between force, extracellular matrix assembly, and substrate …

Role Of E-Cadherin Force In The Spatial Regulation Of Cell Proliferation, Abhinav Mohan

Theses and Dissertations

Cell proliferation and contact inhibition play a major role in maintaining epithelial cell homeostasis. A hallmark of epithelial cells is strong cell-cell junctions. These junctions include E-Cadherin, a type of adherens junction that is critical for both barrier function and contact inhibition. Prior experiments by other groups have shown that adherens junctions are subject to mechanical tension. Externally applied forces (e.g. stretch) results in changes in E-Cadherin forces that coordinate proliferation. My current work tests the hypothesis that E-Cadherin forces mediate the spatial regulation of cell proliferation even in the absence of externally applied forces.

An Investigation Of Kinetic Visual Biofeedback On Dynamic Stance Symmetry, Trisha J. Massenzo

Theses and Dissertations

The intent of the following research is to utilize task-specific, constraint-induced therapies and apply towards dynamic training for symmetrical balance. Modifications to an elliptical trainer were made to both measure weight distributions during dynamic stance as well as provide kinetic biofeedback through a man-machine interface. Following a review of the background, which includes research from several decades that are seminal to current studies, a design review is discussed to cover the design of the modified elliptical (Chapter 2).

An initial study was conducted in a healthy sample population in order to determine the best visual biofeedback representation by comparing different …

A Computational Study Of Curvature In The Outflow Graft Of A Continuous Flow Left Ventricular Assist Device, Laura Patterson

Theses and Dissertations

Left ventricular assist devices (LVADs) are an increasingly utilized therapy for end-stage heart failure. Thrombosis within the graft from the pump to the aorta has been documented, but is poorly researched. This study examines the effect of graft geometry, as measured by radius of curvature, bend angle, and diameter, on thrombogenic flow patterns within the graft for a range of flow conditions. It also examines the effect blood properties, including viscosity and density, on these flow patterns. The results indicated that radius of curvature had a powerful effect on thrombogenic flow patterns. Flowrate and bend angle were also influential. The …

Characterization Of Fibrin Matrix Incorporated Electrospun Polycaprolactone Scaffold, Cho Yi Wong

Theses and Dissertations

Specific objective: Guided tissue regeneration (GTR) aims to regenerate the lost attachment apparatus caused by periodontal disease through the use of a barrier membrane. For the GTR procedures to be successful, barrier membranes are required to be present at the surgical site for an extended period of time (weeks to months). Synthetic membranes have the advantage of prolonged presence in a wound site; however, they do not actively contribute to wound healing. Biologic membranes are recognized by the host tissue and participate in wound healing but have the disadvantage of early resorption. Therefore, the goal of this study is …

Effects Of Cell Adhesion Peptides, Ph, And Matrix Shape On Maintenance Of Breast Cancer Stem Cells In An Engineered Hydrogel Matrix, Leily Daneshian

Theses and Dissertations

Metastasis, resistance to chemo- and radiotherapy, and eventual relapse has been attributed to a tumor subpopulation known as cancer stem cells (CSCs). CSCs are regulated in their tumor microenvironment by various factors. Synthetic hydrogels can be used to investigate the effects of individual environmental factors on CSCs by providing inert 3D matrices. In this thesis, poly ethylene glycol diacrylate (PEGDA) hydrogel with 5kpa modulus has been used as a culture system to study the effect of; I) integrin and heparin binding peptides, 2) pH, and 3) the shape of the microenvironment on breast CSCs maintenance and tumorsphere formation in PEGDA. …

A Handcrafted Multi-Branch Nerve Scaffold For In Vivo Peripheral Nerve Regeneration, Ridwan Fayaz Hossain

Theses and Dissertations

Arm and leg peripheral nerve injuries contribute largely to functional disability. These injuries seldom affect a single-line nerve; rather the injury goes beyond and disrupts the nerve tissue across multiple nerve paths. Here we investigate handcrafted PDMS based multi-branch nerve guidance conduit, which addresses this crucial branching from the sciatic nerve to aid with the regeneration to their appropriate distal targets. The design concept of the developed multiple branch nerve scaffolds is not specific for the sciatic nerve but can be modified for general use of all peripheral nerves and additional applications. Microchannels are also fabricated into a device in …

Impact Of Collagen-Incorporation Within Electrospun Vascular Conduits On The Inflammatory Response And Conduit Mechanics, Karamveer Birthare

Theses and Dissertations

Current surgical alternatives for treating coronary artery diseases are limited in patients with systemic vascular diseases due to unavailability of suitable autologous vessels. The overall goal of this research project is to develop an appropriate tissue engineered vascular grafts (TEVGs) for small-diameter (<6 mm) arteries. Current grafts fail from intimal hyperplasia, caused by hyperproliferation of the smooth muscle cells (SMCs), and graft thrombosis, caused by lack of functional endothelium. Formation of the endothelium, and production of pro-inflammatory species that limits the long term patency, are partially due to the accumulation of oxidized lipid species. In this study, the scaffold composition was systematically varied to assess the inflammatory response and lipid oxidation levels in a rat peritoneal model. Specifically, we determined the collagen to PCL ratio required to limit the production of pro-inflammatory species, while maintaining the required mechanical strength for vascular grafts. Electrospun conduits were prepared from 0%, 10%, and 25% blends of collagen/ PCL (w/w) and implanted in the rat peritoneal cavity for 4 weeks. The results of the study showed that scaffold composition can be varied while keeping the fiber diameter similar. Results from 10% blend conduits showed significantly higher expression for contractile markers compared to the 25% and 0% blend conditions. In general, adding collagen to the PCL conduits reduced the accumulation of oxidized species within the implanted conduits. All conduits exhibited sufficient tensile strength post- implantation. In conclusion, these results demonstrate that introducing 10% collagen into electrospun scaffolds limits the pro-inflammatory characteristics of the recruited peritoneal cells that can potentially improve patency of the TEVGs.

Raman Spectroscopy As A Tool For Single Circulating Tumor Cell (Ctc) Detection And Imaging, Zeid A. Nima

Theses and Dissertations

Breast cancer is the most common type of cancers in the United States. It is imperative that a quick and reliable method for the early detection of circulating tumor cells (CTCs) be identified and tested. In this research several new detection and imaging techniques based on using Raman spectroscopy have been invented. Raman active nano-complex agents based on single-walled carbon nanotubes (SWCNTs) were prepared and used for the swift and specific detection of breast cancer cells. SWCNTs are functionalized with the anti-epithelial cell adhesion molecule (anti-EpCAM) antibody, were able to detect CTCs within 30 min and discriminate few CTCs among …

Ex Vivo Dna Cloning, Adam B. Fisher

Theses and Dissertations

Genetic engineering of microbes has developed rapidly along with our ability to synthesize DNA de novo. Yet, even with decreasing DNA synthesis costs there remains a need for inexpensive, rapid and reliable methods for assembling synthetic DNA into larger constructs or combinatorial libraries. While technological advances have resulted in powerful techniques for in vitro and in vivo assembly of DNA, each suffers inherent disadvantages. Here, an ex vivo DNA cloning suite using crude cellular lysates derived from E. coli is demonstrated to amplify and assemble DNA containing small sequence homologies. Further, the advantages of an ex vivo approach are …

Design And Development Of A Ventilation Chamber For Testing Efficacy Of Tracheal Stents, Caroline N. Horton

Theses and Dissertations

Tracheobronchial malacia results in a weakening of the tracheal walls, leading to increased difficulty breathing. Stents are used to reopen the lumen of the trachea, however, current models are not personalized to each patient, leading to migration, inflammation, and breakage of the stents. In order to successfully test novel stent designs, a ventilation chamber is needed to recreate the breathing conditions of the body.

The following describes the iterative development of a ventilation chamber, which allows inflation and deflation of lungs via negative pressure ventilation, as representative of an actual body undergoing respiration. Previous work shows that lungs are not …

Primary Cilia Mechanotransduction And Microtubule Stability In Mechanically Stretched Lung Adenocarcinoma Cells, Monika Rassi Radhika

Theses and Dissertations

The objective of this study is to investigate the role of microtubule based organelle, the primary cilia in lung adenocarcinoma by i) Quantifying the presence of primary cilia in several Non Small Cell Lung Cancer (NSCLC) cell lines in response to mechanical stimuli, ii) Attempting to determine the role of primary cilia in cell migration, iii) Investigating the effects of Paclitaxel(Taxol) resistance in lung cancer cells, iv) Analyzing the response of lung cancer cells to Smoothened Inhibitors and v) Determining the effects of Transforming Growth Factor Beta-1(TGF-β1) induced Epithelial to Mesenchymal Transition(EMT) in lung cancer cells. To ascertain the effects …

Generation And Delivery Of Charged Aerosols To Infant Airways, Landon T. Holbrook

Theses and Dissertations

The administration of pharmaceutical aerosols to infants on mechanical ventilation needs to be improved by increasing the efficiency of delivery devices and creating better ways of evaluating potential therapies. Aerosolized medicines such as surfactants have been administered to ventilated infants with mixed results, but studies have shown improvement in respiratory function with a much lower dose than with liquid instillation through an endotracheal tube (ETT). An aerosolized medicine must be transported through the ventilation tubing and deposit in the lungs to have the desired therapeutic response.

This work has taken a systematic approach to (i) develop new devices for the …

Evaluation Of A Novel Myoelectric Training Device, Joshua A. Arenas

Theses and Dissertations

Recent technological developments have implemented the use of proportional control in prosthetic hands, giving rise to the importance of appropriate myoelectric control. EMG models in the past have assumed a linear proportionality to simplify the EMG-force relationships. However, it has been shown that a non-linear EMG-force relationship may be a more effective model. This study focused on evaluating three different control algorithms for a novel myoelectric training device, consisting of a toy car controlled by EMG signals from the distal muscles in the arm. Sixteen healthy adult subjects (5 male and 11 female) with an average age of 23.6 years …

The Effects Of Fatigue On Lower Extremity Kinetics And Kinematics In Subjects With Known Ankle Instability, Lindsay E. Clayton

Theses and Dissertations

The goal of this study was to evaluate biomechanical differences between healthy subjects and those with ankle instability during the gradual onset of lower extremity fatigue from a landing activity. An understanding of these differences is needed in order to prevent future injury to or further debilitation in individuals with ankle instability. A functional fatiguing activity was designed to focus fatigue on the quadriceps muscles, as those are the muscles most frequently fatigued during sport. Measures were taken throughout the progression of fatigue with a force plate and a motion tracking system and included vertical ground reaction force and lower …

Peracetic Acid: A Practical Agent For Sterilizing Heat-Labile Polymeric Tissue-Engineering Scaffolds, William R. Trahan

Theses and Dissertations

Advanced biomaterials and sophisticated processing technologies aim to fabricate tissue-engineering scaffolds that can predictably interact within a biological environment at a cellular level. Sterilization of such scaffolds is at the core of patient safety and is an important regulatory issue that needs to be addressed prior to clinical translation. In addition, it is crucial that meticulously engineered micro- and nano- structures are preserved after sterilization. Conventional sterilization methods involving heat, steam and radiation are not compatible with engineered polymeric systems because of scaffold degradation and loss of architecture. Using electrospun scaffolds made from polycaprolactone (PCL), a low melting polymer, and …

Modification And Evaluation Of A Brain Computer Interface System To Detect Motor Intention, Christopher V. Hagerty-Hoff

Theses and Dissertations

It is widely understood that neurons within the brain produce electrical activity, and electroencephalography—a technique used to measure biopotentials with electrodes placed upon the scalp—has been used to observe it. Today, scientists and engineers work to interface these electrical neural signals with computers and machines through the field of Brain-Computer Interfacing (BCI). BCI systems have the potential to greatly improve the quality of life of physically handicapped individuals by replacing or assisting missing or debilitated motor functions. This research thus aims to further improve the efficacy of the BCI based assistive technologies used to aid physically disabled individuals. This study …

Femtosecond Laser Beam Propagation Through Corneal Tissue: Evaluation Of Therapeutic Laser-Stimulated Second And Third-Harmonic Generation, William R. Calhoun Iii

Theses and Dissertations

One of the most recent advancements in laser technology is the development of ultrashort pulsed femtosecond lasers (FSLs). FSLs are improving many fields due to their unique extreme precision, low energy and ablation characteristics. In the area of laser medicine, ophthalmic surgeries have seen very promising developments. Some of the most commonly performed surgical operations in the world, including laser-assisted in-situ keratomileusis (LASIK), lens replacement (cataract surgery), and keratoplasty (cornea transplant), now employ FSLs for their unique abilities that lead to improved clinical outcome and patient satisfaction.

The application of FSLs in medical therapeutics is a recent development, and although …

Computational Modeling To Assess Surgical Procedures For The Treatment Of Adult Acquired Flatfoot Deformity, Brian A. Smith

Theses and Dissertations

Several surgically corrective procedures are considered to treat Adult Acquired Flatfoot Deformity (AAFD) patients, relieve pain, and restore function. Procedure selection is based on best practices and surgeon preference. Recent research created patient specific models of Adult Acquired Flatfoot Deformity (AAFD) to explore their predictive capabilities and examine effectiveness of the surgical procedure used to treat the deformity. The models’ behavior was governed solely by patient bodyweight, soft tissue constraints, and joint contact without the assumption of idealized joints. The current work expanded those models to determine if an alternate procedure would be more effective for the individual. These procedures …

Material Considerations For Development Of 3d Printed Bronchial And Tracheal Stents, Nidah M. Hussain

Theses and Dissertations

Tracheobronchial malacia is a commonly under-diagnosed condition that results in difficulty breathing. The use of a tracheobronchial stent is the best course of treatment for patients whose quality of life has deteriorated due to malacia; unfortunately stents need replacing after issues with inflammation, migration, or eventual stent-breakdown resulting in fistula formation.

The purpose of this thesis is to use three-dimensional (3D) printing technology to improve on existing stents through designing and printing a bioresorbable/biodegradable tracheobronchial stent that can treat tracheobronchial malacia. This was undertaken by testing three biologically favorable materials, type I collagen, polycaprolactone (PCL), and thermoplastic polyurethane (TPU), with …

Automating The Process Of Fabricating Uniform-Sized Cell Spheroids For Three-Dimensional Bioprinting, Ganesh Sosale

Theses and Dissertations

Although researchers have been able to print small, simple, and avascular tissues, they have been unsuccessful in creating large, complex and vascularized organs. Printing large and complex three-dimensional tissues or organs involves utilizing a large quantity of cellular spheroids and layer-by-layer addition of spheroids. In this study, an in-house cell spheroid fabrication system was developed to produce cell spheroids with human liver cells (hepG2), human endothelial cells (hEC), human neural stem cells (hNSC), and induced pluripotent stem cells (iPSC). It offers the ability of fabricating uniform-sized spheroids repeatedly, which is essential when large and complex structures need to be produced. …

Multi-Platform Arabinoxylan Scaffolds As Potential Wound Dressing Materials, Donald C. Aduba Jr

Theses and Dissertations

Biopolymers are becoming more attractive as advanced wound dressings because of their naturally derived origin, abundance, low cost and high compatibility with the wound environment. Arabinoxylan (AX) is a class of polysaccharide polymers derived from cereal grains that are primarily used in food products and cosmetic additives. Its application as a wound dressing material has yet to be realized. In this two-pronged project, arabinoxylan ferulate (AXF) was fabricated into electrospun fibers and gel foams to be evaluated as platforms for wound dressing materials. In the first study, AXF was electrospun with varying amounts of gelatin. In the second study, AXF …