UMD Theses and Dissertations
Permanent URI for this collectionhttp://hdl.handle.net/1903/3
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 given thesis/dissertation in DRUM.
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Item DETERMINING THE EFFECT OF EXTRACELLULAR MICROENVIRONMENT ON TROPHOBLAST INVASION USING A BIOPRINTED PLACENTA MODEL(2017) Kuo, Che-Ying; Fisher, John P; Kim, Peter CW; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality, affecting 8% of all pregnancies. Currently, the only effective treatment for preeclampsia is the premature delivery of the fetus and placenta resulting in significant fetal morbidity. In early pregnancy, fetal trophoblast cells invade and remodel maternal spiral arteries in the uterine wall to create the high capacitance organ of placenta. The uterine spiral arteries in preeclampsia, however, remain narrow and poorly remodeled. The exact mechanisms of how trophoblast invade and remodel the spiral arteriole are not known, and there is a paucity of relevant experimental models to study the mechanisms in human pregnancy. The goal of this work was to develop a dynamic bioprinted placenta model and use it to determine the role of extracellular microenvironment in preeclampsia. We began by developing a 3D placenta model that could quantify trophoblast invasion rates through bioprinting. Then we used decellularization techniques to isolate and established the necessary role of placental basement membrane protein to achieve effective trophoblast invasion. Finally, we used the dynamic bioprinted placenta model and found trophoblast impairs the flow-induced angiogenesis of endothelial cells, a process that plays a central role in preeclampsia. Overall, we described the significant impact of the extracellular microenvironment on the behavior trophoblast and/or endothelial cells, an area that is less investigated but appeared to be critical in the pathogenesis of preeclampsia. Moreover, the approach presented in this work can be used to screen and develop novel therapeutics and biomarkers not only for preeclampsia but also other diseases such as cancer metastasis and wound healing.Item ORBITAL FLOOR REGENERATION USING CYCLIC ACETAL HYDROGELS THROUGH ENHANCED OSTEOGENIC CELL SIGNALING OF MESENCHYMAL STEM CELLS(2009) Betz, Martha Wheaton; Fisher, John P; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Orbital floor fractures are a serious consequence of craniofacial trauma and account for approximately 60-70% of all orbital fractures. Unfortunately, the body's natural response to orbital floor defects generally does not restore proper function and facial aesthetics which is complicated by the thin bone and adjacent sinuses. We propose using a tissue engineering strategy to regenerate orbital floor bone. To this end, a functional biomaterial was investigated to enhance orbital floor regeneration. First, a bone marrow stromal cell population was isolated and differentiation assessed via coculture with chondrocytes and osteogenic media supplements. A cyclic acetal biomaterial composed of the cyclic acetal monomer 5-ethyl-5-(hydroxymethyl)-β,β-dimethyl-1,3-dioxane-2-ethanol diacrylate (EHD) and poly(ethylene glycol) diacrylate (PEGDA) was then developed for cell encapsulation. The previously investigated bone marrow stromal cells were then used to determine the effects of the ammonium persulfate/N,N,N',N'-tetramethylethylenediamine initiator system used to crosslink the EH-PEG hydrogels on cell viability, metabolic activity, and osteogenic differentiation. Next, EH-PEG hydrogels were implanted into orbital floor defects with bone morphogenetic protein-2, where tissue response and surrounding bone growth was analyzed. To improve surrounding tissue interaction and cell infiltration, macroporous EH-PEG hydrogels were created using porogen-leaching. These hydrogels were characterized using optical coherence tomography for pore size, porosity, and cell viability. In addition, these macroporous hydrogels were created with varying architecture to analyze the effects on osteogenic signaling and differentiation. This work outlines the potential application of EH-PEG hydrogels for use in orbital floor repair.Item A Novel Cyclic Acetal Biomaterial and Its Use in Cleft Palate Repair(2006-05-04) Moreau, Jennifer Lynn; Fisher, John P; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Cleft lip and/or palate are the most prevalent congenital craniofacial birth defect in humans. While myriad surgical techniques have been described to repair orofacial clefts, several complications have been associated with the repair techniques. To overcome these complications, a tissue engineering strategy may be employed. In particular, we are investigating strategies for regenerating the alveolar bone that is often missing as a result of cleft palates. Numerous materials have been explored as biomaterials for bone tissue engineering, however there are disadvantages to these, including compromised mechanical properties and harmful degradation products. To overcome this issue, a novel class of biomaterials has been created. These materials are crosslinked networks of monomers of 5-ethyl-5-(hydroxymethyl)-beta,beta-dimethyl-1,3-dioxane-2-ethanol diacrylate. The study presented here was designed to determine the effects of the material's formulation scheme on several of its physical properties, so as to develop a novel bone tissue engineering material suitable for cleft palate repair.