(648f) Development of Silk Protein Conjugates for Mucoadhesive Applications

Polymers that adhere to wet surfaces that are biocompatible, degradable, and devoid of animal-sourced materials are desired for applications as tissue adhesives. Silk from the domesticated silkworm Bombyx mori is a naturally occurring biopolymer with charged hydrophilic terminal regions that endcap a blocky core dominated by hydrophobic domains. Silk was selected for modification for use as an aqueous adhesive because of its high molecular weight, tunable mechanical and degradation properties, aqueous processability, and for its hydrophobicity that was envisioned to afford control over the mechanical properties and aqueous swelling of the modified biopolymers. This work sought to exploit the unique structure and properties of this protein by synthesizing gels that are stable in an aqueous environment and adhere to mucus-covered surfaces. To prepare adhesive hydrogel coatings that can be applied as a liquid and subsequently gel, silk was successfully conjugated with tyramine, a phenol-containing compound capable of being oxidized to a catechol functional group using mushroom tyrosinase (MT). As both aqueous and organic phase syntheses are possible with silk, several solvent systems were investigated to determine the conditions that led to successful coupling without protein aggregation. The silk polymers were characterized to determine composition, adhesive strength using lap shear measurements, cell compatibility and support of proliferation, and their ability to form beta sheets, which physically crosslink silk. Importantly, the conjugation of tyramine showed no effect on silk’s ability to form beta sheets, which may be used to further tune the material’s mechanical properties and degradation profile. These materials afford a new route to synthesize silk-based gels, which we envision to have utility as biodegradable adhesives and sealants.