Title

Enhanced physiological microenvironment for improved evaluation of nanoparticle behavior

Date of Award

2015

Degree Name

M.S. in Bioengineering

Department

Department of Chemical and Materials Engineering

Advisor/Chair

Advisor: Kristen Krupa Comfort

Abstract

Due to their distinctive physicochemical properties, nanoparticles (NPs) have proven to be extremely advantageous for product and application development, but are capable of inducing detrimental outcomes in biological systems. Standard in vitro methodologies are currently the primary means for evaluating NP safety, as vast quantities of particles exist that require appraisal. Here, we developed an enhanced in vitro model that retains the advantages of cell culture, but introduces the key physiological variables of accurate biological fluid and dynamic flow. As NP behavior and subsequent bioresponses are highly dependent upon their surroundings, this developed microenvironment provides a more relevant system to evaluate responses following NP exposure. In this study, the microenvironment is comprised of the A549 lung cell model, artificial alveolar fluid, and dynamic flow at realistic rates; to mimic a NP inhalation exposure. Significant modulations were identified to silver and gold NP characteristics and the nano-cellular interface as a function of particle surface chemistry, fluid composition, and flow condition. More importantly, several of these modifications were dependent on multiple variables, indicating that these responses were previously unidentifiable in a standard cellular environment. Taken together, this study demonstrates that to fully elucidate the behavior and evaluate the safety of NPs, these assessments need to be carried out in a more complex and physiologically relevant cellular exposure model.

Keywords

Nanoparticles Biocompatibility Simulation methods, Nanoparticles Testing, Engineering, Biology, Biomedical Engineering, Materials Science, Ag nanoparticle, enhanced in vitro, artificial alveolar fluid, dynamic flow, tannic acid

Rights Statement

Copyright 2015, author

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