Biomedical Engineering and Bioengineering Commons^™

Novel Approaches For Enhancing Cell Survival And Function In Vivo, Ou Wang

Department of Chemical and Biomolecular Engineering: Theses and Student Research

FDA has approved several cell-based therapeutics and hundreds of cell therapy clinical trials are ongoing. Cells will be a significant type of medicine after small molecule and protein drugs. However, several obstacles need to be addressed to achieve the widespread use of cellular therapeutics. The first challenge is the low efficacy of cell transplantation due to low retention, survival, integration, and function of cells in vivo. The second challenge is producing a massive number of cells for clinical treatment with cost-effectively and reproducibly technologies.

In this thesis, we proposed and investigated two approaches to address these challenges. To begin …

Bioproduction Of Adipic Acid Using Engineered Pseudomonas Putida Kt2440 From Lignin-Derived Aromatics, Howard Willett

Department of Chemical and Biomolecular Engineering: Theses and Student Research

Current industrial synthesis of adipic acid is nonrenewable and depends on a carcinogenic starting material, benzene. Biocatalysis with an engineered microorganism could turn a renewable feedstock into a value-added chemical such as adipic acid. Here we engineered P. putida KT2440 to transform lignin-derived aromatics, coumarate and ferulate, into adipic acid. Lignin is a recalcitrant plant biopolymer burned for thermal energy. Conversion of lignin into a value-added chemical will improve the efficiency of lignocellulose processing plants. The best performing engineered KT2440 strain produces 2.52 mM adipate at a 9.5% (mole/mole) yield. This was achieved by the genetic insertion of non-natural biosynthetic …

Interaction Of Fibrinogen With Fibronectin: Purification And Characterization Of A Room Temperature-Stable Fibrinogen-Fibronectin Complex From Normal Human Plasma, Ayman E. Ismail

Department of Chemical and Biomolecular Engineering: Theses and Student Research

A fibrinogen-fibronectin complex (γγ’pdFI-pdFN) was purified from normal human plasma using a sequence of cryoprecipitation, ammonium sulfate fractionation, and DEAE Sepharose chromatography. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) under reducing condition showed both a 1:1 stoichiometric ratio of fibrinogen (FI) to fibronectin (FN) as well as a stoichiometric ratio of 1:1 of γg to gγ’. The γγ’pdFI-pdFN complex was non-covalent in nature as it was disrupted by affinity adsorption to Gelatin Sepharose where pdFN bound strongly and the disrupted γγ’pdFI fell through the chromatographic column. Surprisingly, the purified γγ’pdFI-pdFN complex was more broadly thermally stable than plasma FI (pdFI) …

Mitochondrial Dysfunction And Loss Of Glutamate Uptake In Primary Astrocytes Exposed To Titanium Dioxide Nanoparticles, Christina L. Wilson

Department of Chemical and Biomolecular Engineering: Theses and Student Research

The proper function of astrocytes is critical for brain health as they are the most abundant cells in the brain which monitor ion homeostasis, recycle neurotransmitters and respond to tissue damage therefore disruption in astrocyte function can result in overall detrimental effects and has been linked with neurodegenerative diseases. Titanium Dioxide (TiO₂) nanoparticles are currently the second most produced engineered nanomaterial in the world with vast usage in consumer products leading to recurrent human exposure. Animal studies indicate significant nanoparticle accumulation in the brain while cellular toxicity studies demonstrate negative effects on neuronal cell viability and function. However, …

Low Molecular Weight Glucosamine/L-Lactide Copolymers As Potential Carriers For The Development Of A Sustained Rifampicin Release System: Mycobacterium Smegmatis As A Tuberculosis Model, Jorge Ragusa

Department of Chemical and Biomolecular Engineering: Theses and Student Research

Tuberculosis, a highly contagious disease, ranks as the second leading cause of death from an infectious disease, and remains a major global health problem. In 2013, 9 million new cases were diagnosed and 1.5 million people died worldwide from tuberculosis. This dissertation aims at developing a new, ultrafine particle-based efficient antibiotic delivery system for the treatment of tuberculosis. The carrier material to make the rifampicin (RIF)-loaded particles is a low molecular weight star-shaped polymer produced from glucosamine (molecular core building unit) and L-lactide (GluN-LLA). Stable particles with a very high 50% drug loading capacity were made via electrohydrodynamic atomization. Prolonged …