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Abstract
Silk fibroin, spun by Bombyx morisilkworms, is a semi-crystalline protein with a high molecular weight. Silk is comprised of hydrophobic blocks and hydrophilic blocks, where the hydrophobic blocks are capable of self-assembling into beta sheet secondary structures and the hydrophilic blocks can be chemically modified using aqueous conditions. The self-assembly of the crystalline domains provide an opportunity to tune the mechanical and degradation properties of the protein. Silk has been fabricated into many different formats including films, hydrogels, and sponges, and has been widely investigated as a biomaterial due to its biocompatibility.
In this dissertation, new synthetic methods were developed to modify silk fibroin to overcome the typically low reported degrees of substitution. The first method used succinic anhydride to enrich the carboxylic acid groups, and it was observed that the synthesis produced silk conjugates with higher molecular weights and degrees of carboxylation than established carboxylation methods. Surfactants and urea were also used with succinic anhydride to disrupt hydrophobic interactions and hydrogen bonding in the hydrophobic regions of the silk, and these additives increased the degree of carboxylation to approximately 90%. The second method used photo-catalyzed oxidation to functionalize the surface of silk films with hydroxyl groups, and modified surfaces displayed a significantly lower contact angle than unmodified silk, indicating that the surface was successfully modified. These synthetic methods were then employed to develop silk conjugates to interface with tissues and cells. The carboxylated silk was coupled with a phenolic compound, tyramine, which was subsequently oxidized with mushroom tyrosinase to form catechol groups that are capable of adhering to different surfaces including tissue. The phenol-enriched silk conjugates were able to form hydrogels and showed superior adhesion to porcine intestine than commercially available tissue adhesives. The hydroxylated silk films were first modified with a bromine compound, which served as an initiator site for surface-initiated atom transfer radical polymerization (SI-ATRP) of acrylate monomers containing a poly(ethylene glycol) (PEG) side chain and a sulfo-betaine zwitterionic side chain. These hydrophilic polymers were hypothesized to reduce protein and cell attachment. Surfaces functionalized with the zwitterionic brush-like polymer successfully reduced the attachment of cells and protein when compared to unmodified silk films.
