Biomedical Engineering and Bioengineering Commons^™

Cell Mechanics In Cardiovascular Disease And Electrospun Scaffold For Vascular Tissue Engineering, Alex Park Rickel

Dissertations and Theses

Cardiovascular disease (CVD) is the leading cause of death worldwide. Atherosclerosis, one of the primary CVDs, is characterized as a chronic inflammatory disease. In the initial stages of atherosclerosis, there is a buildup of cholesterol and lipoproteins that triggers monocytes to enter the arterial wall and begin accumulating lipids. Vascular smooth muscle cells (VSMCs) begin to detach and migrate from the media toward the intima in a process known as phenotypic switching. Phenotypic switching transitions VSMCs from a contractile to synthetic phenotype and they gain the capacity for migration, proliferation, and secretion of extracellular matrix (ECM) proteins. Synthetic VSMCs experience …

Modulation Of Brain Tissue Transport And Endothelial Glycocalyx And Tight Junctions Of The Blood-Brain Barrier By Transcranial Direct Current Stimulation, Yifan Xia

Dissertations and Theses

Transcranial direct current stimulation (tDCS) is a non-invasive approach to treat a broad range of brain disorders and to enhance memory and cognition in healthy individuals. In addition to directly acting on neurons by modulating the membrane potential, inducing neuronal polarization and changing cortical excitability in the brain to achieve its therapeutic effects, prior studies found that tDCS can transiently enhance the permeability (P) of the blood-brain barrier (BBB), the interface between blood circulation and brain tissue. Brain extracellular space (ECS) is a narrow microenvironment which surrounds every cell in the central nervous system (CNS). ECS occupies ~20% of brain …

Development Of A Targeted Drug Delivery System For Intracranial Atheroslerotic Disease, Kirby Fuglsby

Dissertations and Theses

Intracranial atherosclerotic disease (ICAD) remains a leading cause of ischemic events such as stroke. However, the use of drug coated balloons (DCBs) containing paclitaxel (PAT) in the brain vasculature remains limited. This is the result of several factors including particulate shed from polymer excipients, PAT toxicity, and poor blood-brain barrier (BBB) permeability of PAT. Therefore, there is a need for novel PAT and excipient formulations for balloon coatings to improve delivery of PAT to the arterial wall in ICAD while reducing off target drug effects and particulate shed. GM1 has previously been shown to cross the BBB and have high …

Analysis Of Eye Movements To Cartoon Faces In Videos, Kaustubh Sapru

Dissertations and Theses

Saccades are rapid eye movements that move our gaze between successive points of fixation. They are indicative of how we direct our attention and therefore play a role in memory and cognition. For static images, it is established that saccades move faster to faces compared to other objects. We hypothesize that the same is true for videos. To test this hypothesis, saccades to faces in motion pictures have been analyzed. The analysis here entails the recording of saccades to two videos followed by a statistical study of saccades going towards faces or going away from faces. What makes this study …

Framework For The Evaluation Of Perturbations In The Systems Biology Landscape And Inter-Sample Similarity From Transcriptomic Datasets — A Digital Twin Perspective, Mariah Marie Hoffman

Dissertations and Theses

One approach to interrogating the complexities of human systems in their well-regulated and dysregulated states is through the use of digital twins. Digital twins are virtual representations of physical systems that are descriptive of an individual's state of health, an object fundamentally related to precision medicine. A key element for building a functional digital twin type for a disease or predicting the therapeutic efficacy of a potential treatment is harmonized, machine-parsable domain knowledge. Hypothesis-driven investigations are the gold standard for representing subsystems, but their results encompass a limited knowledge of the full biosystem. Multi-omics data is one rich source of …

Novel Mechanisms Of Dc And Kilohertz Electrical Stimulation, Zeinab Esmaeilpour

Dissertations and Theses

Transcranial electrical stimulation is a promising technique where a weak electrical current is applied to the scalp with the goal of modulating brain activity. Understanding the cellular mechanism of direct current (DC) and kilohertz (kHz) electrical stimulation is of broad interest in neuromodulation. More specifically, there is a large mismatch between enthusiasm for clinical applications of the method and understanding of DC and kHz novel mechanisms of action. This dissertation is centered around two main fundamental aims: 1) systematic study of the acute and long-term effects of kilohertz electrical stimulation and amplitude-modulated waveform with kHz carrier frequency using a well-established …

Impact Of Percutaneous Transluminal Intervention On Vascular Hypoxia And The Role Of Micro-Calcifications On Atherosclerotic Plaque Rupture, Andrea Corti

Dissertations and Theses

Atherosclerotic disease is initiated by cholesterol build-up beneath the endothelium, which evolves into a fibroatheroma, a lipid-rich plaque covered by a fibrous cap. Many of these plaques are considered as vulnerable, as they grow to occlude the luminal section of the artery (chronically stenotic) or become mechanically unstable with a higher chance of rupturing (rupture-prone). On one hand, chronically stenotic vulnerable plaques are symptomatic lesions that are often treated with Percutaneous Transluminal Intervention (PTI). Unfortunately, approximately 10% of PTI procedures are followed by severe Neointima Hyperplasia (NH), which causes a new occlusion and failure of the implant. A significant precursor …

Neural Processing Of Semantic Content In Movies, Maximilian Nentwich

Dissertations and Theses

Naturalistic stimuli, such as movies, contain interacting, multimodal and semantic features and allow for free exploration through eye movements. The full extent of neural responses to features such as motion, film cuts and eye movement behavior has not been established. The main hypothesis of this thesis is that complex multimodal and semantic stimuli in naturalistic movies engage a widespread ensemble of locations across the entire brain. To address this question I analyzed simultaneous intracranial and eyetracking data from over 6,000 electrodes across 23 patients with intractable epilepsy. Responses to fast eye movements – saccades – and film cuts are widespread …

Exosome- And Microrna-Based Therapeutic Approach For Tendinopathy, Angela Wang Ilaltdinov

Dissertations and Theses

Tendinopathy, characterized by degeneration and chronic inflammation, is a significant clinical burden. Current treatments focus on symptom management but do not sufficiently address its underlying pathology; however, stem cell-based approaches aimed at repairing diseased tissues may overcome this limitation. Therapeutic effects of stem cells may be due in part to paracrine actions, including some mediated by exosomes – extracellular vesicles secreted by cells that play a role in cell communication. MicroRNA (miRNA), small non-coding RNA carried by exosomes, are likely responsible for many exosome effects. Exosomes and miRNA therapies show promise in treating diseases such as cancer and arthritis, but …

Osseointegration Of A Cementless Total Knee Arthroplasty In A Murine Model Of Glucocorticoid Induced Osteoporosis, Elexis C. Baral

Dissertations and Theses

Glucocorticoid-Induced Osteoporosis (GIOP) is the second largest cause of osteoporosis worldwide. Glucocorticoid-Induced osteoporosis is rapidly, driven principally by deficient osteoblast activity (i.e., decreased bone formation) rather than increased osteoclastic activity. Glucocorticoid-type steroids (GC) are used long-term typically for inflammatory diseases such as rheumatoid arthritis, lupus, multiple sclerosis, and other autoimmune disorders. Inflammatory arthritis often leads to joint replacement at relatively young ages. However, patients who are on GC treatment appear to have poorer outcomes for total joint arthroplasty compared to healthy patients. This is thought to be due to the anti-anabolic effects of GCs and impaired bone healing and osseous …

Computational Model Of Electroconvulsive Therapy Considering Electric Field Dependent Skin Conductivity, Gozde Unal

Dissertations and Theses

Improvements in electroconvulsive therapy (ECT) outcomes have followed refinement in device electrical output and electrode montage. The physical properties of the ECT stimulus, together with those of the patient’s head, determine the impedances measured by the device and govern current delivery to the brain and ECT outcomes. However, the precise relations among physical properties of the stimulus, patient head anatomy, and patient-specific impedance to the passage of current are long-standing questions in ECT research and practice. In this thesis, we develop a computational framework based on diverse clinical data sets. We developed anatomical MRI-derived models of transcranial electrical stimulation (tES) …

Development Of Cellulose-Based, Semi-Interpenetrating Network Hydrogels As Tissue-Adhesive, Thermoresponsive, Injectable Implants, Jesse Martin

Dissertations and Theses

Abstract Development of Cellulose-Based, Semi-Interpenetrating Network Hydrogels as Tissue-Adhesive, Thermoresponsive, Injectable Implants

Hydrogels are three-dimensional polymer networks with high water content and tunable mechanical properties, which have been widely investigated as replacements for soft tissues, such as the intervertebral disc (IVD). Various derivatives of the plant polysaccharide, cellulose, have been explored for use as injectable hydrogel implants. Methylcellulose (MC), which exhibits thermogelation at temperatures above 32°C, and relatively hydrophilic carboxymethyl-cellulose (CMC), are versatile cellulosic polymers that have shown promise as base materials for such applications. In prior work, functionalization with methacrylate groups allowed for the formation of stable, covalently crosslinked …

Low-Intensity Ultrasonic Neuromodulation Of The Rat Hippocampus, Duc Nguyen

Dissertations and Theses

Techniques to non-invasively modulate brain activity are important for mapping human brain circuits, and also for the treatment of a host of neurological and psychiatric disorders marked by aberrant brain activity. Though a wide range of techniques for non-invasive neuromodulation have been proposed, the conventional approaches suffer from significant limitations. Most notably, focal stimulation of deep brain regions is presently only possible with invasive optogenetic and chemogenetic approaches that require craniotomies and genetic access to the brain.

Transcranial focused ultrasound stimulation (tFUS) possesses many of the characteristics desirable from a neuromodulation approach: non-invasiveness, a spatial resolution in the order of …