Engineering Commons^™

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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. …

Enhancing Human Schwann Cells Reparative Behavior Using Heparin/Collagen Layer-By-Layer Coatings, Luis Carlos Pinzon-Herrera

Graduate Theses and Dissertations

When a peripheral nerve injury (PNI) occurs, the gold standard for tissue regeneration is the use of autografts. However, due to the secondary effects produced by multiple surgeries involved in the removal and implantation of autografts for very small lesions, it is possible to replace them with the use of Nerve Guide Conduits (NGCs). However, NGCs are limited to short lesions (less than 1 cm). This limitation is caused by the absence of compounds in the extracellular matrix (ECM) that autografts can provide. Since much of the regenerative process takes place on the NGC surface, our work aims to modify …

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 …

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 …

Increasing Production Of Therapeutic Mabs In Cho Cells Through Genetic Engineering, Charles Barentine

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Between 2014 and 2018, the global market for therapeutic monoclonal antibodies (mAbs) rose from $60 billion to $115.2 billion with a projected value of $300 billion by 2025. These molecules are used to effectively treat some of the most challenging illnesses from auto-immune diseases to cancer. While mAbs are highly valuable with potent applications, their production at scale remains an outstanding challenge. These molecules are largely produced in Chinese Hamster Ovary (CHO) cells that require highly specific conditions to produce a useful product.

Genetic engineering presents one solution to overcome productivity limits. With the advent of CRISPR (clustered regularly interspaced …

Low Resource Assay For Tracking Sars-Cov-2 In Wastewater, Julissa Van Renselaar

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Wastewater based epidemiology (WBE) allows for the tracking of nucleic acid of SARS-CoV-2 in wastewater which gives the opportunity for the public and government officials to be informed about the infectivity of the virus in a community. Advances have been made in WBE that have allowed for higher performance, lower resource use, and faster turnaround time. An adapted concentration method of spin column direct extraction has yielded a proxy virus recovery of 83%, consumable cost of $2.01 per sample, and a turnaround time of 0.33 hour/sample. Other concentration methods have lower proxy virus recoveries, comparable cost, and comparable turnaround time. …

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 …

Engineer And Test A Biodegradable Microneedle Patch To Deliver Meloxicam For Managing Pain In Cattle, Katherine Alejandra Miranda Munoz

Graduate Theses and Dissertations

Microneedle patches are a promising source for transdermal diffusion of macromolecules and are designed to painlessly penetrate the skin. In this study, a biodegradable chitosan microneedle patch to deliver meloxicam for managing pain in cattle was tested. The potential of reuse of the polymeric solution to fabricate the patches, optimization of fabrication, morphological analysis of the microneedle patch and analysis of preservation of the chemical composition after sterilization were evaluated. In-vitro analysis consisted of studying in-vitro penetration mechanical properties, compression testing analysis of microneedle patch, and in-vitro drug release analysis. In-vivo studies were performed to analyze the dissolution capability of …

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 …

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 …

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 …

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

Honors Theses

No abstract provided.

Seeing The Big Picture: System Architecture Trends In Endoscopy And Led-Based Hyperspectral Subsystem Intergration, Craig M. Browning

<strong> Theses and Dissertations </strong>

Early-stage colorectal lesions remain difficult to detect. Early development of neoplasia tends to be small (less than 10 mm) and flat and difficult to distinguish from surrounding mucosa. Additionally, optical diagnosis of neoplasia as benign or malignant is problematic. Low rates of detection of these lesions allow for continued growth in the colorectum and increased risk of cancer formation. Therefore, it is crucial to detect neoplasia and other non-neoplastic lesions to determine risk and guide future treatment. Technology for detection needs to enhance contrast of subtle tissue differences in the colorectum and track multiple biomarkers simultaneously. This work implements one …

Iron Nanoparticles For Magnetic Imaging Applications, Aleia Williams

Masters Theses

Extensive research on iron oxide nanoparticles for various applications including nanomedicine, energy applications, environmental remediation, and magnetic imaging have previously been performed. Many are currently FDA approved as magnetic resonance imaging contrast agents and tracers for magnetic particle imaging applications. Magnetic properties of such materials are crucial to obtain good contrast and resolution. However, studies have shown the magnetic properties of iron oxide nanoparticles are less in comparison to those found in pure iron nanoparticle.

This research involves the synthesis and characterization of iron nanoparticles for applications in magnetic resonance imaging contrast agents, magnetic particle imaging tracers, and therapeutic agents …

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 …

Encapsulation Of Antimicrobial Peptides In Bicontinuous Microemulsions For Topical Delivery To Surgical Site Infections And Chronic Wounds, Madison A. Oehler

Masters Theses

Surgical site infections and chronic wounds, especially those caused by antibiotic-resistant microorganisms, result in hospitalization and fatalities each year. Methods to prevent these infections, such as cleaning and preparing medical tools, have had minimal success in preventing infections. Further, antibiotic treatments have become less successful in treating infections and wounds because of antibiotic-resistant bacteria. Antimicrobial peptides (AMP) are a possible treatment solution for wound infections. AMPs are oligopeptides that occur in nature or can be synthesized in vitro which possess a broad spectrum of antimicrobial activity against bacteria and other harmful microorganisms. AMPs operate by disrupting the packing arrangements of …

Importance Of Light Activation For Plant Cryptochrome And Antibacterial Drug Delivery Strategies, Merfat Ahmed Hammad

Theses and Dissertations

The goal of this project is to investigate the benefits of applying light in different systems. In the first part, the magnetoreception process that occurs in the light activated cryptochrome of Arabidopsis Thaliana was investigated. In the second part, photo-carbon monoxide releasing molecules (photo-CORMs) were investigated for their antibacterial effect to develop biomedical strategies. Overall, this has been achieved in three different studies. The first study investigated if the forward lightdriven reaction is involved in the magnetoreception process or not in cryptochrome (CRY). To accomplish this, the plant seedlings were tested for 90 minutes as follows: 5 minutes in the …

Investigating The Role Of Cryptochrome Activity In Arabidopsis Plant And Blue Light Exposure In Saos-2 Cell-Mediated Mineralization, Maria Nijr Albaqami

Theses and Dissertations

Cryptochromes (CRYs) are flavoproteins that absorb blue light and are associated with the perception of electromagnetic stimuli in a variety of organisms including animals and plants. When exposed to blue light, CRYs undergo flavin redox cycles and form radical pairs intermediates that are assumed to be magnetically sensitive as predicted by the radical-pair hypothesis. However, it is unknown if CRYs fulfill the criteria to act as biological magnetosensors. In the first aim, Arabidopsis thaliana seedlings were exposed to blue light and a time-dependent weak magnetic field at radiofrequency (RF) of 7 MHz as a diagnostic tool to test the radical-pair …

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, …

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 …