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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Item Breast Cancer Type 1 Susceptibility Protein is a Critical Regulator of Skeletal Muscle Lipid Metabolism(2013) Jackson, Kathryn Campbell; Spangenburg, Espen E; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)This dissertation research consists of three investigations in an effort to determine how circulating estrogens affect skeletal muscle lipid metabolism. Loss of circulating estrogens results in significant increases in visceral fat mass and intramuscular lipids (IMCL). These increases in lipid storage are strongly associated with an elevated risk of developing type 2 diabetes. The first investigation examined how the loss of circulating estrogens alters skeletal muscle metabolic function. Ovariectomy (OVX) resulted in significantly higher visceral fat mass and fatty acid sarcolemmal transporter content, which corresponded with elevated IMCL. Skeletal muscle in the OVX group exhibited lower acyl carnitine species suggesting impaired lipid flux through the mitochondria. Lastly, mitochondrial oxygen consumption rates were impaired in OVX skeletal muscle fibers. The results from this study gave rise to a search to identify an estrogen- sensitive mechanism that regulated lipid transport into the mitochondria. Study two determined for the first time that the BRCA1 protein, which is encoded by an estrogen-sensitive gene, is present and functions as an integral regulator of lipid metabolism in skeletal muscle. Specifically, BRCA1 binds to acetyl CoA carboxylase in response to acute exercise. The in vitro induction of decreases in BRCA1 expression resulted in higher IMCL content, reduced mitochondrial oxygen consumption rates, and elevated reactive oxygen species production. Surprisingly, no differences in BRCA1 content were detected between males and females. In the final study, an inducible, skeletal-muscle specific, BRCA1 KO mouse was developed. Ablation of BRCA1 in skeletal muscle resulted in exercise intolerance and the development of kyphosis. Contrary to our hypothesis, loss of functional BRCA1 in skeletal muscle attenuated the negative metabolic consequences of chronic high fat diet exposure. Collectively, these data provide strong rationale that BRCA1 is an important regulator of skeletal muscle metabolic function and further provide evidence that BRCA1 function is critical in multiple tissues across the body.Item The Delivery of IGF-1 for Skeletal Muscle Regeneration Within Abdominal Wall Hernia Repair(2009) Falco, Erin Elizabeth; Fisher, John P.; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)At an ever increasing pace, synthetic biomaterials are being developed with specific functionalities for tissue engineering applications. These biomaterials possess properties including biocompatibility, mechanical strength, and degradation as well as functionalities such as specific cell adhesion and directed cell migration. However, synthetic polymers are often not completely biologically inert and may non-specifically react with the surrounding in vivo environment. An example of this reactivity is the release of acidic degradation products from hydrolytically degradable polymers based upon an ester moiety. These degradation products can lower the local pH and incite an inflammatory response as well as increase scaffold degradation rate. Therefore there has been a concerted effort in the research community to develop alternatives. In order to address this concern, a novel class of biomaterials based upon a cyclic acetal unit has been developed and investigated for both soft and hard tissue repair. This work specifically looks at a cyclic acetal biomaterial based on a 5-ethyl-5-(hydroxymethyl)-β,β-dimethyl-1,3-dioxane-2-ethanol diacrylate (EHD) monomer as a scaffold for abdominal wall hernia repair. Abdominal wall hernias are a growing concern for clinicians today as they occur in approximately 10% of all patients that undergo an abdominal procedure. Despite many advances in repair techniques, both wound healing and skeletal muscle regeneration is limited in many cases. This results in both a decrease in abdominal wall tissue function as well as a hernia recurrence rate of up to 50%. To address this high recurrence rate this project aims to create a functional gene delivery scaffold from the EH monomer. Scaffolds with different architectures were fabricated and skeletal muscle myoblast cell compatibility, material properties and protein and gene delivery rates were all investigated.Item The Development of EH Networks for Skeletal Muscle Regeneration within Abdominal Wall Hernias(2007-05-02) Falco, Erin E.; Fisher, John P; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Incisional hernias are a common clinical problem occurring in up to 10% of all patients undergoing abdominal incisions. Current repair techniques involve the placement of xenografts, allografts, or prosthetic biomaterials. Despite these techniques, the incidence of hernia recurrence ranges from 24% to 54%. In order to address these high recurrence rates, we propose using a skeletal muscle engineering strategy. To this end, the novel cyclic acetal biomaterial, 5-ethyl-5-(hydroxymethyl)-β,β-dimethyl-1,3-dioxane-2-ethanol diacrylate, was functionalized to promote skeletal muscle regeneration. It was found that this biomaterial promotes myoblastic cell attachment and proliferation as well as the delivery of functional insulin-like growth factor 1 proteins in vitro; therefore demonstrating the scaffolds biocompatibility. Furthermore, mechanical properties of the scaffold were tested and the complex modulus was shown to decrease after a significant increase in initiator concentration. Overall, this work establishes the functionality of a degradable cyclic acetal as a scaffold for skeletal muscle engineering.