All ETDs from UAB

Advisory Committee Chair

Mansoor N Saleh

Advisory Committee Members

Charles A Monroe

Patsy G Oliver

Selvum Pillay

Uday K Vaidya

Mark L Weaver

Document Type

Dissertation

Date of Award

2018

Degree Name by School

Doctor of Philosophy (PhD) School of Engineering

Abstract

Cancer is poised to become the leading cause of death worldwide with lifetime probability of 1-in-2 men and 1-in-3 women developing cancer. Despite this, research and development of new treatment options remains expensive and slow, in part, due to inadequate disease models, therapy evaluation assays, and absence of delivery control in leading treatment options. These factors also impede patient-specific personalized medicine. Electrohydrodynamic atomization (EHDA) fabrication technologies, such as electrospinning (ESp) and electrospraying (ESy), offer promising nanomedicine pathways toward addressing these challenges. ESp has garnered much interest in tissue engineering but is dwarfed by softlithography in microphysiological systems (MPS), including lab-chip platforms, for investigating disease progression and treatment evaluation. However, porosity of in vivo scaffolds, which is integral to barrier and interface functions, is either absent in lab-chip systems or, if present, introduces considerable cost, complexity, and an unrealistic uniformity in pore geometry. We address this by integrating nanofibrous porous scaffolds produced using ESp, instead of softlithography, to better recapitulate the in vivo microenvironment for modeling transport, air-liquid interface, and tumor progression. Similarly, despite commercial success in other sectors, ESy lags in nanomedicine applications, including precision drug delivery systems (DDS). In this study, we use emergent coaxial ESy techniques to produce core-shell, drug-loaded, ultrasound-responsive microbubbles (MBs) that can safely encapsulate drug formulations, until released on-demand, to improve bioavailability and potency while reducing systemic toxicity. Further, we show that our MBs are superior to those produced using current standard for gas-filled MBs. Despite its strengths and versatility, EHDA adoption for such applications is constrained by reproducibility and scaling challenges. Ironically, the principle governing EHDA – interplay among interfacial tension, gravity, mechanical forces, and electric fields – also adds a dimension of instability to it. Variations in interfacial tension from changes in equipment, material composition or concentration, or environmental parameters, can dramatically diminish stability, alter properties of resulting fibers or bubbles, or both. In order to mitigate this, we devised an in situ surface and interfacial tension measurement method specifically for EHDA applications. This method uses signal processing algorithms to correlate frequency and periodicity of liquid dispensed in EHDA microdripping mode with numerical solutions from computational fluid dynamics models.

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Engineering Commons

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