Theses and Dissertations from UMD
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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
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Item EFFECTS OF 3D PRINTED VASCULAR NETWORKS ON HUMAN MESENCHYMAL STEM CELL VIABILITY IN LARGE BONE TISSUE CONSTRUCTS(2015) Ball, Owen Matthew; Fisher, John P; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)There is a significant clinical need for engineered bone graft substitutes that can quickly, effectively, and safely repair segmental bone defects. One emerging field of interest involves the growth of engineered bone tissue in vitro within bioreactors, the most promising of which, are perfusion bioreactors. Utilizing a tubular perfusion system bioreactor, which allows media to perfuse freely around alginate scaffolds laden with human mesenchymal stem cells, large-scale bone constructs can be created by simply aggregating these beads together in the desired shape. However, these engineered constructs lack inherent vasculature and quickly develop a necrotic core, where no nutrient exchange occurs. Through the use of 3D printed vascular structures, used in conjunction with a TPS bioreactor, cell viability after just one day of aggregation was found to increase by as much as 50 percent in the core of these constructs, with in silico modeling predicting construct viability at steady state.Item USE OF 3D PRINTED POLY(PROPYLENE FUMARATE) SCAFFOLDS FOR THE DELIVERY OF DYNAMICALLY CULTURED HUMAN MESENCHYMAL STEM CELLS AS A MODEL METHOD TO TREAT BONE DEFECTS(2014) Wang, Martha Elizabeth Ottenberg; Fisher, John P; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)This project investigates the use of a tissue engineering approach of an absorbable polymer, poly(propylene fumarate) (PPF) to provide long term mechanical stability while delivering a bioactive material, precultured human mesenchymal stem cells (hMSC) encapsulated in hydrogel, to repair bone defects. Annually over 2.2 million bone grafting procedures are performed worldwide; however, current treatment options are limited for critically sized and load bearing bone defects. Much progress has been made in development of bone tissue replacements within the field of bone tissue engineering. The combination of a polymer scaffold seeded with cells for the eventual replacement by host tissue has shown significant promise. One such polymer is PPF, a synthetic linear polyester. PPF has been shown to be biocompatible, biodegradable and provide sufficient mechanical strength for bone tissue engineering applications. Additionally PPF is able to be photocrosslinked and therefore can be fabricated into specific geometries using advanced three-dimensional (3-D) rapid prototyping. Current technology to culture and differentiate hMSCs into osteoblasts has been enhanced with the development of the tubular perfusion system (TPS). The TPS bioreactor has been shown to enhance osteoblastic differentiation in hMSCs when encapsulated in alginate beads. Although this system is effective in differentiating hMSCs it lacks the sufficient mechanical strength for the treatment of bone defects. Therefore this work suggests a combination strategy of harnessing the ability of the TPS bioreactor to enhance osteoblastic differentiation with the mechanical properties of poly(propylene fumarate) to develop a porous PPF sleeve scaffold for the treatment of bone defects. This is accomplished through four steps. The first step investigates the cytotoxicity of the polymer PPF. Concurrently the second step focuses on designing, fabricating and characterizing PPF scaffolds. The third step investigates the degradation properties of 3D printed porous PPF scaffolds. The fourth step characterizes alginate bead size and composition for use within the PPF sleeve scaffolds. The successful completion of these aims will develop a functional biodegradable bone tissue engineering strategy that utilizes PPF fabricated scaffolds for use with the TPS bioreactor.Item TUBULAR PERFUSION SYSTEM BIOREACTOR FOR THE DYNAMIC CULTURE OF HUMAN MESENCHYMAL STEM CELLS(2012) Yeatts, Andrew Bryan; Fisher, John P; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)In vitro culture techniques must be improved in order to increase the feasibility of cell based tissue engineering strategies. Limitations of current techniques are largely a result of the slow diffusion of molecules such as oxygen into the interior of three dimensional scaffolds in static culture. In order to enhance nutrient transport we have developed a novel bioreactor, the tubular perfusion system (TPS), to culture human mesenchymal stem cells (hMSCs) in three dimensional scaffolds. In our design, hMSCs are cultured on scaffolds tightly packed in a tubular growth chamber. Media is perfused by a peristaltic pump through the growth chamber and around the tightly packed scaffolds. In the first part of the work hMSCs are encapsulated in alginate scaffolds and results demonstrate bioreactor culture enhances late osteoblastic differentiation of hMSCs. An investigation into shear stress in the system revealed that osteogenic markers increase with increasing shear stress and that the differentiation of hMSCs is dependent on cell radial position within scaffolds. In order to enhance the ability to implant these constructs in vivo, a method to create an aggregated cell containing construct in vitro in a bioreactor system was developed. In this part of the work hMSCs are cultured in individual alginate beads in the TPS bioreactor and the beads are aggregated to form one large construct. Following this the TPS bioreactor was investigated to culture synthetic poly-L-lactic acid scaffolds which were fabricated using supercritical carbon dioxide gel drying. In addition to investigating the effects of perfusion on hMSC growth in these scaffolds, the effect of microporosity was investigated. In the final part of the work, a study was completed to determine how TPS culture influenced in vivo bone regeneration. Here alginate beads as well as synthetic PLGA/PCL constructs were used as scaffolds. Results revealed the efficacy of using the tubular perfusion system for bone tissue engineering and demonstrated increased bone formation as a result of hMSC implantation in both alginate and PLGA/PCL scaffolds. These studies highlighted the need for bioreactor culture in vitro as well as scaffolds to support in vivo tissue interaction.