Theses and Dissertations from UMD

Permanent URI for this communityhttp://hdl.handle.net/1903/2

New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a give thesis/dissertation in DRUM

More information is available at Theses and Dissertations at University of Maryland Libraries.

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    Effects of exercise and inflammation on circulating microparticles
    (2024) Heilman, James; Prior, Steven J.; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Circulating microparticles (MPs), a subset of extracellular vesicles, have been implicated as novel biomarkers connected to vascular dysfunction. As such, they may contribute to atherosclerosis, hypertension, and other conditions leading to cardiovascular disease. MPs are involved in cell-to-cell communication in response to apoptosis and activation of the immune and inflammatory response, transferring their contents to nearby cells and effectively spreading each condition. The objective of this dissertation was to explore how circulating MP number and function are affected by stimuli such as diet and exercise. Our first study examined how post-prandial inflammation caused by a high-fat meal affects circulating MP number and function in young, healthy adults. We determined that a high fitness level may have a protective effect against the inflammatory load posed by a high-fat meal. The second study determined the effects of acute high-intensity interval aerobic exercise versus acute moderate intensity continuous aerobic exercise on circulating MP number and function in overweight versus lean recreationally active adults. We found that MPs and arterial stiffness in overweight individuals are differentially impacted by the type of acute exercise. Our findings suggest that overweight individuals undergo a greater inflammatory response following high-intensity exercise compared to lean. The third study investigated the effects of a 6-month aerobic exercise training program on circulating MP counts and function in previously sedentary older adults. While we found no effect of the exercise training program on MPs, we provide insight into how improvements in cardiovascular fitness as well as higher exercise intensities may be needed to see changes in MP number and function following aerobic exercise training in older adults. For the first time, we have shown that both dietary inflammation and acute exercise can significantly impact MP function. Furthermore, we have shown that fitness status and body composition play important roles in determining MP number and function after each stimulus. Our findings provide novel insight into how MPs contribute to various types of inflammation as well as how they may be used as biomarkers to measure the progression of cardiovascular disease.
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    Bio-Inspired Polymer Microparticles for Targeted Recognition and Response
    (2014) Arya, Chandamany; Raghavan, Srinivasa R.; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Microbeads and microcapsules are container structures that are frequently used in biomedical applications. In this dissertation, we have sought to impart new functionalities to these particles, inspired by phenomena observed with biological cells. We have engineered polymer microparticles that recognize and respond to specific species from the surroundings (e.g. cells, polymer chains, metal ions). Three classes of new microparticles are reported, which are each reminiscent of a different type of biological cell in terms of recognition capabilities and response. In the first part of this dissertation, we create functionalized microbeads from the biopolymer, chitosan, and use these to selectively recognize and capture Circulating Tumor Cells (CTCs) from blood. The microbeads are functionalized with a protein (streptavidin) and packed into an array within a microfluidic device. Blood samples with biotin-labeled CTCs are flowed over the packed bed of chitosan beads. Similar to how macrophages adhere to foreign bacteria (i.e. antibody-antigen interactions), the streptavidin-labeled chitosan beads can selectively recognize and adhere to the biotin-labeled CTCs. We show that such a packed bed of chitosan beads could serve as an inexpensive platform for customized capture of different rare cells (cancer cells, stem cells etc) from blood. In the next study, we develop a class of microbeads that undergo clustering (aggregation) in the presence of specific polymers. The inspiration for this comes from the cells (e.g., platelets) and polymers involved during the formation of blood clots. Our system consists of chitosan microbeads coated with cyclodextrins (sugar molecules with a hydrophobic binding pocket), which are then exposed to a polymer that is decorated with hydrophobic units. The particles bind to the polymer chains via hydrophobic interactions and in turn, the particles are induced to form clusters. Subsequently, the polymer precipitates and forms a matrix around the particle clusters, leading to a structure that is reminiscent of a blood clot (platelets enveloped by a mesh of fibrin chains). Lastly, we develop a class of microparticles that have the ability to selectively destroy other microparticles. The inspiration here is from the body's immune system, where cells like the killer T cells selectively destroy cancer and virus infected cells without harming healthy cells. Towards this end, we synthesize two types of microparticles: chitosan capsules that contain the enzyme glucose oxidase (GOx), and beads of a different biopolymer, alginate that are crosslinked with copper (Cu2+) ions. The chitosan capsules enzymatically convert glucose from the surroundings into gluconate ions. When these capsules approach the alginate/copper beads, the gluconate ions chelate the copper ions, leading to the disintegration of the alginate beads. Other beads that do not contain Cu2+ are not affected in this process.