Biomedical Engineering and Bioengineering Commons^™

Tumor Targeting Gold Nanoparticles For Delivery Of Rna And Dna Oligonucleotide Therapies For Glioblastoma., Nicholas Allen

Electronic Theses and Dissertations

Glioblastoma (GBM) brain tumors are highly aggressive gliomas due to genetic and cellular heterogeneity. Current GBM treatment consists of surgical resection of the tumor combined with radio- or chemo-therapies. While these treatments have increased the life expectancy for GBM patients up to 20 months, they have had little effect on the 5-year survival rate. The complex cellular and genetic composition of the tumor makes current treatments less effective long term. One approach to developing more effective GBM treatments is to customize nanoparticle-based drug delivery systems that can directly target the aberrant gene expression patterns within a particular GBM tumor. Delivery …

Metabolomic Differentiation Of Tumor Core And Edge In Glioma., Mary E. Baxter

Electronic Theses and Dissertations

Glioma is one of the most aggressive forms of brain cancer. It has been shown that the microenvironments differ significantly between the core and edge regions of glioma tumors. This study obtained metabolomic profiles of glioma core and edge regions using paired glioma core and edge tissue samples from 27 human patients. Data was acquired by performing liquid-liquid metabolite extraction and 2DLC-MS/MS on the tissue samples. In addition, a boosted generalized linear machine learning model was employed to predict the metabolomic profiles associated with O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation.

A panel of 66 metabolites was found to be statistically significant …

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 …

Characterization Of Fundamental Parameters That Modulate Acoustofluidic-Mediated Molecular Delivery To Cells., Connor Sterling Centner

Electronic Theses and Dissertations

Cell-based therapies represent the latest biotechnological revolution in medicine, but significant limitations exist in non-viral intracellular delivery techniques during manufacturing of cell therapies. To address these limitations, a novel acoustofluidic device was developed to deliver ultrasound waves into a flow chamber for rapid molecular delivery to human cells. Our acoustofluidic device delivers biomolecules by inducing expansion and collapse of exogenous gas-filled microbubbles (“cavitation”), which enhances molecular delivery to nearby cells. Experimental studies were conducted to characterize key parameters that influence acoustofluidic-mediated molecular delivery to human cells. A clinical ultrasound transducer was generally utilized with varying cationic microbubble concentrations. Intracellular delivery …

Development And Applications Of In-Vitro And In-Silico Models Of The Cardiovascular System To Study The Effects Of Mechanical Circulatory Support., Moustafa Meki

Electronic Theses and Dissertations

Cardiovascular diseases (CVDs) are the leading cause of mortality globally. With ongoing interest in CVDs treatment, preclinical models for drug/therapeutic development that allow for fast iterative research are needed. Owing to the inherent complexity of the cardiovascular system, current in-vitro models of the cardiovascular system fail to replicate many of the physiological aspects of the cardiovascular system. In this dissertation, the main concern is with heart failure (HF). In advanced HF, patients may receive Left Ventricular Assist Devices (LVADs) as a bridge to transplant or destination therapy. However, LVADs have many limitations, including inability to adapt to varying tissue demand …

Investigation Of Cardiovascular Tissue Following 56fe-Radiation And Potential Countermeasure Effectiveness., Alexandra R Decarlo

Electronic Theses and Dissertations

Exposure to ionizing radiation is an important medical concern because it can lead to health problems including cancer and cardiovascular issues. In space, astronauts are exposed to ionizing radiation that is not experienced by those who remain on Earth. This radiation can cause health problems such as cardiovascular disease. One way this can happen is through the creation of reactive oxygen species, which can activate TGF-β1, contributing to fibrosis or other cardiovascular problems. Antioxidants can be a potential pharmacological mitigator of these excess reactive oxygen species because of their ability to neutralize reactive oxygen species. One such antioxidant with potential …

Plga-Modified Nanoparticles For The Treatment Of Hypo-Vascularized Hpv-Related Cervical Cancers., Lee B. Sims

Electronic Theses and Dissertations

A major challenge associated with delivery of active agents in the female reproductive tract (FRT) is the ability of agents to efficiently diffuse through the cervicovaginal mucosa (CVM) and reach the underlying sub-epithelial immune cell layer and vasculature. A variety of drug delivery vehicles have been employed to improve the delivery of agents across the CVM and offer the capability to increase the longevity and retention of active agents to treat infections of the female reproductive tract. Nanoparticles (NPs) have been shown to improve retention, diffusion, and cell-specific targeting via specific surface modifications, relative to other delivery platforms. In particular, …

Restoring Cholesterol Homeostasis In Familial Hypercholesterolemia Cell Line Model, Lubna Hindi

Electronic Theses and Dissertations

Familial hypercholesterolemia (FH) is an autosomal dominant disorder that results in elevated levels of low-density lipoprotein cholesterol (LDL-C). This increase in serum cholesterol level has been shown to result in premature coronary artery disease (CAD) with devastating symptoms from a young age. Today, the prevalence of heterozygous FH (HeFH) and homozygous FH (HoFH) is estimated to be 1 in 320 and 1 in 160,000 people, respectively. FH is referred to as an underdiagnosed disease due to the large number of mutations that continues to grow. These mutations often exist in one of or a combination of three genes: low-density lipoprotein …

Development And Evaluation Of A Biocompatible Electroactive Sensor For Continuous Blood Pressure Measurement., Scott D. Cambron

Electronic Theses and Dissertations

Piezo-active composites have been implemented for sensing and transduction for decades. The 0-3 ceramic/polymer composite is one of the most common composite types used for sensing applications, owing to their tailorable properties of the two-phase composition, consisting of a three-dimensionally connected polymer/rubber matrix (inactive phase) with a dispersion of isolated piezo-ceramic particles (active phase). This thesis describes a method to develop novel biocompatible perivascular band comprised of a two-phase piezo-active composite to be fabricated using simple manufacturing processes. Biomaterials such as tissue scaffolds comprised of silk fibroin (SF) and chitosan (CS), and biocompatible soft rubbers will be implemented as the …