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Improving The Stimulation Selectivity In The Human Cochlea By Strategic Selection Of The Current Return Electrode, Ozan Cakmak

Dissertations

The hearing quality provided by cochlear implants are poorly predicted by computer simulations. A realistic cochlear anatomy is crucial for the accuracy of predictions. In this study, the standard multipolar stimulation paradigms are revisited and Rattay’s Activating Function is evaluated in a finite element model of a realistic cochlear geometry that is based on µ-CT images and a commercial lead. The stimulation thresholds across the cochlear fibers were investigated for monopolar, bipolar, tripolar, and a novel (distant) bipolar electrode configuration using an active compartmental nerve model based on Schwartz-Eikhof-Frijns membrane dynamics. The results suggest that skipping of the stimulation point …

Angiogenic Supports For Microvascular Engineering, Zain Siddiqui

Dissertations

Ischemic tissue disease is caused by a lack of circulation / blood supply to tissue. This can be treated by introducing a number of angiogenic (pro-blood vessel forming) factors into the tissue. This work presents strategies for ischemic tissue treatment utilizing a novel proangiogenic self-assembling peptide hydrogel platform. To demonstrate the utility of this platform, its use alone as an angiogenic therapeutic (both alone as a self-assembling hydrogel and with two-component systems), and its ability to vascularize implants is explored. Due to these angiogenic scaffolds demonstrating efficacy to regenerate microvasculature, this work evaluates diseases that can be treated by the …

Advancing Fluorescent Contrast Agent Recovery Methods For Surgical Guidance Applications, Brook Kennedy Byrd

Dartmouth College Ph.D Dissertations

Fluorescence-guided surgery (FGS) utilizes fluorescent contrast agents and specialized optical instruments to assist surgeons in intraoperatively identifying tissue-specific characteristics, such as perfusion, malignancy, and molecular function. In doing so, FGS represents a powerful surgical navigation tool for solving clinical challenges not easily addressed by other conventional imaging methods. With growing translational efforts, major hurdles within the FGS field include: insufficient tools for understanding contrast agent uptake behaviors, the inability to image tissue beyond a couple millimeters, and lastly, performance limitations of currently-approved contrast agents in accurately and rapidly labeling disease. The developments presented within this thesis aim to address such …

Engineering The Development Of Neuromuscular Circuitry On-Chip, Inès Khiyara

Electronic Theses and Dissertations

Neuromuscular development happens in a complex interconnected network of biochemical pathways. This complicated embryonic development follows a strong, functional, and precise neuromuscular network that has interested both scientists and engineers who seek to better understand neuromuscular diseases. These disorders can be inherited or acquired, and their severity and mortality can vary. Researchers first studied the neuromuscular network from an organismal perspective, and more recently from an embryological, cellular, molecular, biochemical, and genetic perspective. From these studies, the fundamental principles of motor neuron pathfinding to muscles are widely understood, but the molecular drivers of specific nerve-muscle pairing remain unknown. Although in …

Functionalized Plasmonic Nanostructures For Ultrasensitive Single Cell Analysis, Priya Rathi

Arts & Sciences Electronic Theses and Dissertations

Ultrasensitive detection and quantification of soluble, secreted and cell surface-bound proteins is critical for advancing our understanding of cellular systems, enabling effective drug development, novel therapies, and bio-diagnostics. However, exiting technologies are largely limited by their sensitivity, making the detection and quantification of low-abundant proteins extremely challenging. This forms a major barrier in various fields of biology and biomedical sciences. In this work, we introduce novel cellular analysis methodologies based on plasmon-enhanced fluorescence for analyzing cell structure and probing surface and secreted proteins from cells. In the first part, we introduce plasmon-enhanced expansion microscopy and demonstrate the effectiveness of employing …

Development Of A Crosslinked Osteochondral Xenograft And A Collagen Stabilizing Intra-Articular Injection To Remediate Cartilage Focal Lesions To Prevent Osteoarthritis, Mark Lewis Mosher

Theses and Dissertations

Osteoarthritis is one of the most common causes of disability in adults in America. It is a progressive and degenerative disease where the articular cartilage is broken down and lost from the surfaces of bones causing chronic pain and swelling in the joints, and currently has no cure. The most commonly osteoarthritis starts from a focal lesion on the cartilage surface, which will expand on the surface and downwards through the thickness of the tissue. The current gold standard for correcting cartilage focal lesions is the osteochondral autograft/allograft transplantation (OAT), which replaces the defect with a fresh osteochondral graft. The …

Oxidized Fibrin Alginate Microbeads To Treat Vascular Calcification, Brittany Nichole Macha

Theses and Dissertations

Calcification is linked to a high prevalence of cardiovascular events and mortality due to arterial stiffness. Stiffening of the arteries in the case of medial calcification is due to hydroxyapatite mineral deposited in the artery thus leading to the loss of elastin. A possibility of removing this rogue mineral along the vessel walls could be the use of osteoclasts. Osteoclasts, a type of osteocyte, have the unique ability to absorb bone in the bone turnover process. It is proposed that in the future, osteoclasts be delivered to the site of mineralization through oxidized alginate-fibrin microbeads. Alginate hydrogels have proven great …

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

ETD Archive

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 …

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

ETD Archive

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. …

Evaluation Of Cellulose Nanocrystal Inks And Their Structural Characteristics For 3d Bioprinting Of Customized Scaffolds, Patrick William Kuczwara

Graduate Theses and Dissertations

3D bioprinting of biological scaffolds requires control of the physicochemical properties of each unique structures. A promising material for control of properties is hydrogels, which can help create biomimetic scaffolds with controlled spatial arrangement of materials by integrating biological materials directly into layers during the bioprinting process. Nanocellulose offers a unique combination of properties including mechanical, biomimetic, and biocompatibility. These properties offer flexibility over the types, shapes, and applications of their printed hydrogel scaffolds, (i.e., tissue, drug, encapsulation). However, 3D bioprinting of nanocellulose-based hydrogels requires high loading percentages (i.e., >10 wt%) or chemical crosslinkers (i.e., bis(acyl)phosphane oxides (BAPO)). High solid …

Deciphering The Firing Patterns Of Hippocampal Neurons During Sharp-Wave Ripples, Kourosh Maboudi Ashmankamachali

Theses and Dissertations

The hippocampus is essential for learning and memory. Neurons in the rat hippocampus selectively fire when the animal is at specific locations - place fields - within an environment. Place fields corresponding to such place cells tile the entire environment, forming a stable spatial map supporting navigation and planning. Remarkably, the same place cells reactivate together outside of their place fields and in coincidence with sharp-wave ripples (SWRs) - dominant electrical field oscillations (150-250 Hz) in the hippocampus. These offline SWR events frequently occur during quiet wake periods in the middle of exploration and the follow-up slow-wave sleep and are …

Color Resolved Cherenkov Imaging Allows For Differential Signal Detection In Blood And Melanin Content, Vihan A. Wickramasinghe

Dartmouth College Master’s Theses

Cherenkov imaging in radiation therapy allows a video display of the irradiation beam on the patient’s tissue, for visualization of the treatment. High energy radiation from a linear accelerator (Linac) results in the production of spectrally-continuous broadband light inside tissue due to the Cherenkov effect; this light is then attenuated by tissue features from transport and exits from the delivery site. Progress with the development of color Cherenkov imaging has opened the possibility for some level of spectroscopic imaging of the light-tissue interaction and interpretation of the specific nature of the tissue being irradiated. Generally, there is a linear relationship …

The Influence Of Electrical Stimulation Pulse Frequency Of Macro-Sieve Electrode On Rat Sciatic Nerve Detection Threshold, Jingyuan Zhang

McKelvey School of Engineering Theses & Dissertations

No abstract provided.

Evaluating The Viscoelastic Properties Of Alligator Skin Gelatin, Alligel, Compared To Mammalian And Fish Gelatins, Sarah E. Jimenez

Honors Theses

No abstract provided.

An Integrated Electronic-Skin Patch For Real-Time And Continuous Monitoring Of A Panel Of Biomarkers Combined With Drug Delivery, Tanzila Noushin

Electrical Engineering Theses

Inflammatory biomarkers present in the human body play a vital role in medical field by guiding the clinician in decision-making for many diseases. The levels of these inflammatory biomarkers are associated with the severity and progress of several diseases. Researchers have found that increasing severity of many diseases such as cardiovascular disease, after surgery infection, and adverse clinical outcomes due to infectious diseases, results in the elevation of the level of inflammatory biomarkers in human sweat. Furthermore, the inflammatory cytokines indicate the pathophysiology and prognosis of critically ill SARS‑CoV‑2 patients. In this thesis work, different sensors have been developed for …

Investigating Spatial Heterogeneity In Myocardial Wound Environments To Improve Therapy, Michael Potter

All Dissertations

Heart failure is a broad pathology manifestation categorized by an inability of the heart to successfully pump blood throughout the vast vessel network of the body. Within the United States, heart failure is projected to increase by approximately 46% from 2012 to 2030. Modalities of heart failure are generally related to wall mechanics that are impacted following myocardial infarction events. Interplay exists between the wall mechanics, responding cell populations, and the spatial heterogeneities in the resultant scar. This interplay directs the myocardium towards heart failure modalities governed by overly stiff or compliant states. It is essential to elucidate details underlying …

In Vitro Bioreactor For Mechanical Control And Characterization Of Tissue Constructs, Samuel Coeyman

All Dissertations

Heart failure (HF) currently affects over 6 million Americans, 50% of whom die within 5 years of their initial diagnosis. A major contributor to the onset of HF is cardiac fibrosis in the myocardium, which arises when fibroblasts (FBs) are activated in response to heightened mechanical stress from overload conditions like hypertension. Activated FBs remodel the extracellular matrix (ECM) and secrete ECM proteins including collagen. FB remodeling has been studied in the past by applying forces and/or deformations to three-dimensional, cell-seeded gels and tissue constructs in vitro. Unfortunately, previous stretching platforms have traditionally not enabled mechanical property assessment to be …

Scalable Data-Driven Predictive Modeling And Analytics For Cho Process Development Optimization, Sarah Mbiki

All Dissertations

In 1982, the FDA approved the first recombinant therapeutic protein, and since then, the biopharmaceutical industry has continued to develop innovative and highly effective biological drugs for various illnesses¹. These drugs are produced using host organisms that are modified to hold the genetic encoding of the targeted protein¹. Of the many host organisms, Chinese hamster ovary (CHO) cells are often used due to capability to perform posttranslational modification (PTM): which allows human-like synthesis of proteins unlikely to invoke immunogenicity in humans ^1,2.

Despite all the positive attributes, many challenges are associated with CHO cell cultures, …

Development Of A Tissue Engineered Cardiac Patch, Howard Herbert

All Dissertations

Cardiovascular Disease(CVD) is the leading cause of mortality in the developed world. CVD is most commonly manifested as atherosclerosis of the coronary arteries leading to Myocardial Infarction(MI). After MI, fibrosis of the ventricular wall leads to heart failure(HF), a pandemic affecting 26 million people globally. While therapies are continuously developed to combat HF, the treatment of choice, whole heart transplant, is limited by the availability of donor hearts. It is clear that there is a need to develop a long-term solution to combat HF and its enormous economic burden. Tissue Engineering and Regenerative Medicine holds promise as a possible solution …

Tibial Compression During Activities Of Daily Living In Young And Older Adults, Elijah Miles Walker

Boise State University Theses and Dissertations

Introduction: Stress fracture, particularly in the tibia, is a growing concern among older adults (greater than 65 years). Older adults may have inherent stress fracture risk from ageing-related changes to their musculoskeletal system. Specifically, older adults reduced ankle neuromuscular function may impair their ability to attenuate repetitive compressive forces experienced during daily locomotor tasks and increase the likelihood of suffering bone damage from decreased bone tissue elasticity. Yet, it is currently unknown if older adults exhibit greater tibial compression than their younger counterparts during locomotor tasks. Purpose: This study sought to quantify tibial compression for older and younger adults when …

The Role Of Generative Adversarial Networks In Bioimage Analysis And Computational Diagnostics., Ahmed Naglah

Electronic Theses and Dissertations

Computational technologies can contribute to the modeling and simulation of the biological environments and activities towards achieving better interpretations, analysis, and understanding. With the emergence of digital pathology, we can observe an increasing demand for more innovative, effective, and efficient computational models. Under the umbrella of artificial intelligence, deep learning mimics the brain’s way in learn complex relationships through data and experiences. In the field of bioimage analysis, models usually comprise discriminative approaches such as classification and segmentation tasks. In this thesis, we study how we can use generative AI models to improve bioimage analysis tasks using Generative Adversarial Networks …

Re-Engineering Cardio-Oncology Testing Using Biomimetic Heart Slice Cultures., Jessica Miller

Electronic Theses and Dissertations

28% of drug withdrawal from the market are due to unforeseen disruptions in cardiomyocyte contractility and electrophysiology. The most commonly used platforms for drug testing are in vivo animal models and in vitro cell culture models. While both have been of paramount importance for the discovery and detection of many cardiotoxicities and mechanisms of action, they lack the ability to model an intact human myocardium. This work aims to establish cardiac tissue slices, which are 300-micron thin tissue sections taken from the left ventricular myocardium, as an alternative platform for cardio-oncology studies, specifically cardiotoxicity testing. Additionally, this work aims to …

Optimized 3d-Printing Of Carbon Fiber-Reinforced Polyether-Ether-Ketone (Cfr-Peek) For Use In Overmolded Lattice Composite, Ryan C. Ogle

Masters Theses

Current orthopedic implants are overwhelmingly composed from metallic materials. These implants show superior mechanical properties, but this can additionally result in stress shielding due to a modulus mismatch between the bone tissue and implanted device. Polymeric implants reduce this stress shielding effect but have much lower mechanical properties, limiting their use. Polylactic acid (PLA) is a widely used biodegradable thermoplastic polymer, however, its use has been limited by the polymer’s mechanical properties and rapid loss of strength during degradation in vivo. Polyether-ether-ketone (PEEK) is another common biocompatible polymer , with chemical and mechanical properties which make it a popular alternative …

Targeted Drug-Loaded Nanoparticle System (Tdnps) To Ameliorate And Treat Idiopathic Lung Fibrosis, Harish Ramachandramoorthy

Bioengineering Dissertations

Idiopathic pulmonary fibrosis (IPF) is a fatal progressive disease with a dismal prognosis and 3-5 years of survival. Up to date, there are no effective treatments, and a few current therapies that do not ameliorate the pulmonary fibrosis but rather just increase the survival time by 2-3 years. The major factor limiting the treatment is the lack of targeted therapies to deliver the drugs past the mucosa, into the disease microenvironment. To combat this disease, we proposed a localized therapy via our targeted drug-loaded nanoparticles (TDNPs) to effectively deliver drugs and treat lung fibrosis. Our objective was to design TDNPs …

An In Vitro 3d Model To Investigate Iol: Posterior Lens Capsule Interactions On Lens Epithelial Cell Responses, Joyita Roy

Bioengineering Dissertations

ABSTRACT: Posterior Capsule Opacification (PCO) is the most common complication associated with Intraocular Lens (IOL) implantation. The disease is caused by the infiltration and proliferation of Lens Epithelial Cells (LEC) into the interface between the IOL and Posterior Lens Capsule (PLC). The severity of these cell responses depends on a lot of factors like the IOL design, IOL material, and interaction between the IOL and the posterior lens capsule. While some studies have also shown that adsorption of certain proteins present in the PLC, like fibronectin, may affect IOL-induced PCO in the clinical setting, the mechanism governing such interactions is …

Highly Adherent Antimicrobial Coatings For Orthopedic Implants, Mikhail Bredikhin

All Dissertations

Fracture-related infections (FRIs) are the most devasting sort of complications associated with fracture fixation devices, as they lead to patients’ morbidity, prolonged hospitalization, amputations, and even death.External fixators additionally suffer from pin site infections (PSIs), which initiate at the skin entry points of the skin-metallic pin interface present in the external fixation of the damaged bones, often causing deep tissue infection and osteomyelitis. Small percutaneous pins, commonly known as Kirschner wires (K-wires), are used to treat complex fractures and deformities.They are drilled inside the diseased bone for the healing period and are left protruding outside the skin for fixation adjustments …

Development Of Enzyme-Responsive Polymersomes As A Drug Delivery System For Gm1 Gangliosidosis, Bipin Chakravarthy Paruchuri

All Dissertations

GM1 gangliosidosis is a lysosomal storage disorder caused by deficiency of β-galactosidase (βgal) and subsequent accumulation of GM1 ganglioside in lysosomes. The rare nature of this disorder presents challenges with prognosis and treatment. Enzyme replacement therapy (ERT) can effectively treat systemic deficiencies, but the intravenously administered enzyme cannot cross the blood-brain barrier (BBB) to treat the central nervous system. A delivery system to encapsulate and deliver the enzyme can facilitate enzyme transport across the BBB with suitable surface modifications. One of the pathological aspects of GM1-affected cells is the upregulation of the lysosomal enzyme hexosaminidase A (HexA). In this dissertation, …

The Role Of Mri In Diagnosing Autism: A Machine Learning Perspective., Yaser Elnakieb

Electronic Theses and Dissertations

There is approximately 1 in every 44 children in the United States suffers from autism spectrum disorder (ASD), a disorder characterized by social and behavioral impairments. Communication difficulties, interpersonal difficulties, and behavioral difficulties are the top common symptoms. Even though symptoms can begin as early as infancy, it may take multiple visits to a pediatric specialist before an accurate diagnosis can be made. In addition, the diagnosis can be subjective, and different specialists may give different scores. There is a growing body of research suggesting differences in brain development and/or environmental and/or genetic factors contribute to autism development, but scientists …

Image-Based Cancer Diagnosis Using Novel Deep Neural Networks, Hosein Barzekar

Theses and Dissertations

Cancer is the major cause of death in many nations. This serious illness can only be effectivelytreated if it is diagnosed early. In contrast, biomedical imaging presents challenges to both clinical institutions and researchers. Physiological anomalies are often characterized by modest modifications in individual cells or tissues, making them difficult to detect visually. Physiological anomalies are often characterized by slight abnormalities in individual cells or tissues, making them difficult to detect visually. Traditionally, anomalies are diagnosed by radiologists and pathologists with extensive training. This procedure, however, demands the participation of professionals and incurs a substantial expense, making the classification of …

Establishing The Efficacy Of Non-Cellular Components Of Adipose-Derived Stromal Vascular Fraction In Promoting Angiogenesis., Daniel Benson

Electronic Theses and Dissertations

Microvascular disease is hallmarked by pathophysiological conditions such as endothelial senescence, intimal thickening which impairs vasodilation, and regression of the capillary beds causing tissue ischemia in the myocardium or in peripheral vascular networks. Adipose-derived stromal vascular fraction (SVF) has previously demonstrated the ability to revascularize tissue. Increasing evidence shows that regenerative cells elicit their therapeutic benefit by paracrine mechanisms, leaving open extracellular vesicles (EVs) as a potential crux of the cell therapy paradigm. To test this idea, three types of gelatin methacrylate hydrogels were employed: SVF gels, EV gels derived from SVF, and blank control gels, which were used in-vitro …