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Engineering substrates to enhance cell-material interactions and nonviral gene delivery
Understanding the relationship between material surface properties and cellular responses to these properties is essential to designing biomaterial surfaces that are biocompatible, capable of promoting cell adhesion, spreading, and proliferation, and enhancing the delivery of therapeutics, such as DNA, for gene delivery and tissue engineering applications. Chemical and physical techniques to fabricate uniform or non- uniform surface modifications presenting distinct chemical functional groups or nanotopographies are effective strategies to enhance biomolecule immobilization and cell-material interactions. In this dissertation, both chemical and physical surface modifications were investigated for their potential to influence biomolecule adsorption and cell-material interactions. Alkanethiol self-assembled monolayers (SAMs) were used to provide surfaces with highly defined surface chemistries to evaluate the influence of substrate characteristics, such as substrate hydrophobicity and charge, on cell-material interactions, such as cell adhesion, spreading, viability, and proliferation in the context of enhancing nonviral gene delivery. Alkanethiol SAMs were also used to provide chemically defined surfaces to study the immobilization of electrostatically complexed DNA to substrates for substrate-mediated gene delivery applications. In addition to chemical surface modifications, sculptured thin films (STFs), which provide uniform columnar nanotopographies, were used to examine the effects of physical modifications of surface nanotopography on cell-material interactions (adhesion, spreading, proliferation) and for their ability to load biomolecules, such as proteins and polymers. Additionally, a combinatorial generalized ellipsometry and quartz crystal microbalance with dissipation analytical technique was extensively used to examine the immobilization and loading of polymers, DNA, and proteins to both flat and three-dimensional nanostructured surfaces. The investigations presented in this dissertation reveal both chemical and physical surface characteristics that are conducive to promoting cell- material interactions, demonstrate the ability of biomolecule loading within nanostructured thin films, and develop new substrates for enhancing cell-material interactions with the potential to deliver therapeutic biomolecules for biomaterial, tissue engineering, and nonviral gene delivery applications. ^
Engineering, Biomedical|Nanotechnology|Engineering, Materials Science
Kasputis, Tadas, "Engineering substrates to enhance cell-material interactions and nonviral gene delivery" (2014). ETD collection for University of Nebraska - Lincoln. AAI3615941.