Design of Silica-Collagen Nanocomposite for Corneal Replacement
2015-09
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Design of Silica-Collagen Nanocomposite for Corneal Replacement
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2015-09
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The cornea is the most commonly transplanted tissue in the United States. Globally, corneal diseases are the second leading cause of blindness. Due to strict FDA regulations, lack of eye banking facilities, and other factors which limit the supply of donor tissue, designing an artificial cornea made of readily available materials is of great interest. The synthetic constructs that are currently clinically available in the United States have had moderate success, but biocompatibility issues such as stromal melting and epithelial defects are still common. When considering a potential material for corneal replacement, it must meet the design criteria of the normal functioning cornea. The relevant design criteria can be broken down into three main groups: optical behavior, biomechanical properties, and biocompatibility. The presented work proposes silica-collagen nanocomposites as a viable candidate material to meet these design criteria. A bottom-up approach starting from the molecular level is utilized to modify the surface chemistry and physical properties of collagen fibrils. In doing so, methodologies are presented which allow for fine-tuning of optical, biomechanical, and biodegradation behavior. The first part of this work validates the theory that light scattering of collagen hydrogels is heavily dependent on the change in the material’s index of refraction over length scales comparable to the wavelength of incident light. This work shows that light scattering of collagen hydrogels can be minimized by a rapid neutralization technique, and by the addition of nanocrystalline cellulose. Additionally, collagen hydrogels with embedded magnetic nanowires can be polarized to form an aligned fibril microstructure and show an increase in light transmission. The second part of this thesis characterizes the mechanical and optical behavior, as well as the biocompatibility of silica-collagen nanocomposites. This work shows that a copolymerization method can be used to make implants which have improved biomechanical properties (when compared to pure collagen hydrogels) and can be re-epithelialized in an ex vivo rabbit model. Additionally, an improved two-step process for silica deposition onto collagen fibrils is presented. This new method shows that poly-L-lysine can be used to induce a uniform silica shell around collagen fibrils in the absence of large silica aggregates. This new method increases mechanical stiffness and enzymatic degradation resistance without producing any additional light scattering in the material. Silica-collagen nanocomposites show great potential in the context of corneal replacement. The methods developed and results presented here can be useful for improving any collagen-based corneal replacement, as well as in other applications such as drug delivery and silica nanoparticle templating.
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University of Minnesota Ph.D. dissertation. September 2015. Major: Mechanical Engineering. Advisor: Allison Hubel. 1 computer file (PDF); xvii, 157 pages.
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DiVito, Michael. (2015). Design of Silica-Collagen Nanocomposite for Corneal Replacement. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/181718.
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