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Characterization of Meta-Keratin Biomaterials Derived from Human Hair: Applications for Fiber Development

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abstract
Over the past 60 years, biomaterials for medical applications have evolved from industrial, off-the-shelf metals and ceramics to naturally-derived materials capable of mimicking the dynamic biochemical, structural and mechanical roles of the biological environment. Among these, keratin biomaterials derived from human hair have been used for a variety of biomedical applications due to their intrinsic biocompatibility and ability to regulate cellular behavior. The main objective of this dissertation work was to test the effect of increased surface area on the biological characteristics of human hair-derived keratin biomaterials. Since the bioactivity of keratin materials is believed to be largely controlled by surface-mediated mechanisms that are dependent on physical contacts between the cells and material, we hypothesized that keratin biomaterials with increased surface area, such as nanostructured fibrous materials, would allow for increased cell-material interactions and increased bioactivity. The ability to create nanofibrous keratin materials, however, has previously been limited by the intrinsically poor mechanical properties of pure, naturally-derived biomacromolecules. Therefore, our approach to creating novel keratin fibers first involved an in depth study of the relationship between material composition and function. By understanding how the composition of our protein system affects the overall physical, mechanical and biological properties, we were able to manipulate our hair extracts to obtain a solution of well-characterized and purified, high molecular weight keratins that were more suitable for fiber formation. Electrospinning techniques were used to create high surface area, fibrous keratin materials that showed enhanced capabilities for cellular interactions and binding. For these studies, platelets isolated from whole blood were used since keratin hydrogels have previously been shown to have hemostatic characteristics due to their ability to initiate platelet adhesion and activation leading to thrombus formation. In additional studies, the specific mechanisms underlying cellular adhesion to keratin biomaterials were investigated in greater detail by assessing the involvement of specific surface receptors on hepatocytes to fractionated keratin materials. This work showed that keratin composition and structure are important for cellular adhesion and that unlike traditional cell-ECM interactions, hepatocyte interactions with keratin biomaterials may not be integrin-mediated. Together, these analyses grant insight into the mechanisms responsible for the excellent bioactivity of keratins and establish methods for modulating this activity in order to optimize biomaterial performance. Ultimately, these findings will have important implications for the next era of keratin biomaterial development by enabling the creation of novel materials designed to function specifically for targeted applications, such as the application of fibrous keratin materials for hemostasis.
subject
biomaterials
cellular interactions
fiber
keratin
structure-function relationship
contributor
Richter, Jillian Rouse (author)
Van Dyke, Mark E (committee chair)
Saul, Justin (committee member)
Harrison, Benjamin (committee member)
Hudson, Samuel (committee member)
Holmes, James (committee member)
date
2011-07-14T20:35:04Z (accessioned)
2011 (issued)
degree
Biomedical Engineering (discipline)
identifier
http://hdl.handle.net/10339/33426 (uri)
language
en (iso)
publisher
Wake Forest University
title
Characterization of Meta-Keratin Biomaterials Derived from Human Hair: Applications for Fiber Development
type
Dissertation

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