Biomedical Engineering and Bioengineering Commons^™

Methods For Objective Determination Of Musculoskeletal Coordinate Systems, Tara Francesca Nagle

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Joint mechanics research relies on joint kinematics and kinetics measurements, represented from relative relationships of local coordinate systems (CS) belonging to bones of the joint. It’s common to define these CSs from anatomical landmarks, which are sensitive to observer variability and often don’t result in CS that best represent the functional motion of the joint. This work is presented in three articles addressing the following aims: 1) to develop a method to objectively define coordinate systems through optimization of unique passive movement paths, 2) to develop an alternative method to objectively define coordinates systems for joints with non-unique passive movement …

Influence Of Ligament Locations And Activity Profiles On Risk Of Knee Injury In Adolescents, Alexandria Mallinos

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The Anterior Cruciate Ligament (ACL) is the most commonly injured ligament in the body. The overall goal of this project is to develop patient-specific computational pediatric knee models that can accurately predict the in vivo biomechanical environment of the ACL. The foundation of this research is broken down into three specific parts: 1) model construction, 2) model validation, and 3) model application.

Specific Aim #1 developed anatomically accurate specimen-specific finite element representations of pediatric tibiofemoral joints. The models were able to demonstrate the ability for the Open Knee cruciate stereolithography (stl) files to be three-dimensional scaled to create subject-specific ligaments …

Site-Specific Glyco-Engineering Of Recombinant Thrombomodulin, Joseph M. Keil

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Thrombomodulin (TM), a membrane glycoprotein predominately expressed on endothelium, plays essential roles in regulating local hemostatic balance. Particularly, TM modulates the activity of thrombin from a procoagulant to an anticoagulant protease. When bound to TM, thrombin activates plasma protein C, which selectively inactivates coagulation factors Va and VIIIa. At the same time, TM-bound thrombin is unable to cleave fibrinogen or to activate platelets diminishing its procoagulant activity. recombinant TM456 is a promising anticoagulant candidate, but it has a very short half-life. TM is a proteoglycan and its O-linked glycosaminoglycan (GAG), chondroitin sulfate (CS), on the D3 domain contributes to TM’s …

Motion Analysis Of Feeding Tasks: Brachial Plexus Versus Control Subjects, Madison M. Lovette

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Brachial plexus birth injuries (BPBI) occur in about 0.4 to 4.6 of every 1000 live births due to stretching or tearing of the nerves. Children with BPBI often struggle to perform daily living activities without assistance, including feeding themselves. Upper extremity function is commonly assessed in children with BPBI using the modified Mallet classification, a set of positions representing activities of daily living that are scored according to ability. The hand to mouth position is a Mallet position and is often used to represent feeding tasks in the BPBI population. Establishing this normative data will provide a baseline for comparison …

Predictions Of Indentation Stiffness Of Musculoskeletal Regions Using Ultrasound, Sean Doherty

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Tissue indentation response is an important metric for understanding how different musculoskeletal regions respond to loading and is a function of the tissue’s form. Modem imaging techniques provide information about the internal structures of human tissue. Ultrasound remains one of the most common imaging techniques performed, given its portability and low costs. Prior work and data collection on 100 patients involved the collection of ultrasound images at eight different locations across the musculoskeletal extremities. Given the tissue structure information that the medical imaging provided, it was hypothesized that the mechanical properties of the tissue could be predicted from this data. …

Lipids Affect The Diffusion Of Estradiol In Osteonal Bone, Nicholas Anthony Cimino

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In healthy osteonal bone, embedded osteocytes form an intercellular communication network through overlapping cell membrane extensions, possibly defining an overlooked and clinically relevant lipid-mediated transport pathway for nonpolar molecules. Previous techniques evaluating solute transport in cortical bone limit tissue analysis to microscale areas (less than 1 mm2) using tracers and assumptions that diminish clinical relevance, presenting the need for an improved method to evaluate solute diffusion in macroscale areas (greater than 1 mm2) of osteonal bone. A new diffusion system - constructed of glass and polytetrafluoroethylene - was designed and validated for this purpose, exhibiting minimal adsorption of solutes and …

An Improved Polynomial Chaos Expansion Based Response Surface Method And Its Applications On Frame And Spring Engineering Based Structures, Mhd A. Hafez

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In engineering fields, computational models provide a tool that can simulate a real world response and enhance our understanding of physical phenomenas. However, such models are often computationally expensive with multiple sources of uncertainty related to the model’s input/assumptions. For example, the literature indicates that ligament’s material properties and its insertion site locations have a significant effect on the performance of knee joint models, which makes addressing uncertainty related to them a crucial step to make the computational model more representative of reality. However, previous sensitivity studies were limited due to the computational expense of the models. The high computational …

Implementation Of Microfluidic Mixers For The Optimization Of Polymeric, Gold, And Perovskite Nanomaterials Synthesis, Alexa Roberts

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I would like to thank Dr. Chandra Kothapalli for the opportunity to participate in this research project and the continuous guidance he has given me in all aspects of the lab work. I would like to acknowledge the entire Chemical and Biomedical Engineering Department for their assistance throughout the program, for partially supporting my tuition and stipend through teaching assistantships, and the opportunities to present and discuss my research project with other interested students and faculty. I would like to acknowledge Dr. Petru Fodor and Dr. Geyou Ao for their support as members of my defense committee. Additionally, I would …

Interaction Between The Metabolism Of Ketone Bodies In Brain Tissue And Neurological Disorders, Chan-Chih Hsiao

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Regulation of brain metabolism and cerebral blood flow involves complex control systems with several interacting variables at both cellular and organ levels. Quantitative understanding of the spatially and temporally heterogeneous brain control mechanisms during internal and external stimuli requires the development and validation of a computational (mathematical) model of metabolic processes in brain tissue. A computational model of the biochemical pathways in brain is presented in this paper. The model structure consists of neurons, astrocytes, and a surrounding capillary network. Glucose is the major oxidative energy substrate in the brain. However, under hypoglycemic conditions such as during diet or fasting …

Developing A Multifunctional Thermo-Responsive Viral Like Particle (Vlp) Platform With New Physicochemical Characteristics, Sepehr Dejdar

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Smart materials are a class of material whose physical characteristics change significantly in a controllable fashion once exposed to an external stimulus such as stress, pH, light, temperature, etc. If the temperature is the external stimuli (control variable) the material is termed thermo-responsive. Out of numerous thermo-responsive materials, elastin-like polypeptide (ELP) is a well-known protein-based biopolymer. Protein cages are well-defined biological nanostructures which are highly symmetrical and monodisperse. This class of proteins are both chemically and genetically tunable, making them a suitable recipient of new properties. Protein re-engineering is the basis of developing a hybrid platform (e.g. polymer-protein) to deliver …

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

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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

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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. …

Measurement Of Red Blood Cell Oxygenation State By Magnetophoresis, Nina A. Smith

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Magnetophoresis of red blood cells (RBCs) at varying partial pressures of oxygen (pO2) is hypothesized to rejuvenate stored blood to be utilized beyond the FDA regulated 42-day storage time. Magnetophoresis is a particle or cells motion induced by an applied magnetic field in a viscous media. The average magnetophoretic mobility of an oxygenated RBC is -0.126x10-6 mm3-s/kg, and a deoxygenated RBC is 3.66x10-6 mm3-s/kg, presenting magnetophoresis as a resource for RBC rejuvenation in hopes of storing it longer than 42 days. The main objective of this paper was to determine if controlling the pO2 within an RBC suspension, can singly- …

Modeling Liver Diseases Using Hepatic Cell Microarrays, Alexander David Roth

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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 …

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

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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. …

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

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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 we …

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

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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 intervention …

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

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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 electric motors …

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

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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.

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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

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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 1296 …

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

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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

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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 alginate …

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

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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 …

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

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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 …

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

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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.

Decitabine-Loaded Nanogel Treatment To Reverse Cancer Drug Resistance, Samantha A. Cramer

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Cancers in which epigenetic changes, such as hypermethylation of DNA, lead to drug resistance cause the cancer to become unresponsive to existing chemotherapeutic treatments. The epigenetic drug – 5-aza-2’-deoxycytidine (decitabine, DAC) – is a potent hypomethylating agent, but its effect is transient due to its instability. Previous studies have shown that loading DAC into nanogel significantly enhances its antiproliferative effect (compared to DAC in solution) in drug-resistant breast cancer cells (MCF-7/ADR). Further, the previous studies demonstrated changes in the membrane lipid profile of resistant cells following treatment with DAC either as solution or in nanogels. The objective of the present …

Design And Production Of A Hydrogel Forming Polypeptide: Engaging High School Students In Protein Design, James K. Deyling

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Bioinks are a class of hydrogel that have the potential to be the ink used in the creation of printed organs, connective tissue, and other important structures within the body. One class of material that may be a suitable bioink hydrogel is elastin-like polypeptides (ELPs), which are synthetic biopolymers inspired by the naturally existing connective tissue elastin. ELPs consist of a repeat pentapeptide sequence (GXGVP)n, where X is any of the 20 naturally existing amino acids other than proline. These biomolecules are capable of exhibiting environmental responsiveness when exposed to certain stimulus such as salt concentration, temperature, and pH, depending …

Time And Temperature Dependent Surface Tension Measurements Of Responsive Protein-Based Polymer Surfactant Solutions, Hakan Celik

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A three-armed star elastin-like polypeptide (ELP-foldon) has thermoreversible character which exhibits phase separation above a transition temperature (Tt) in physiologic salt concentrations. At lower salt concentration, the ELP-foldon behaves like a thermoresponsive surfactant, exhibiting micelle formation above its Tt. The purpose of this study is characterize the surfactant behavior of the ELP-foldon at air-liquid interface by measuring the surface tension. The surface tension is measured as a function of time for different ELP concentrations from 10 nM to 50 ℗æM and over range of temperatures from 25 to 35 ℗¿ using the axisymmetric drop shape analysis (ADSA). The ADSA is …

Solute Partitioning In Elastin-Like Polypeptides: A Foundation For Drug Delivery Applications, Eric Helm

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No abstract provided.