Artificially Engineered Protein Polymers for Functional Regenerative Tissue Scaffolds

Abstract

Polymeric hydrogels, with their high-water content resembling the extracellular matrix, show great promise as extracellular matrix (ECM)-mimicking biomaterials for treating cardiovascular diseases in tissue engineering and regenerative medicine applications. Modulating the mechanical properties, such as elasticity, of hydrogels is crucial for directing stem cell fate and achieving desired tissue regeneration outcomes. However, replicating the intricate nanomechanics of natural proteins in the ECM and cardiac tissues is challenging. This is because the chemical cross-linking between protein polymers is considered nonspecific, given the diverse side chains found in the amino acids. To address this issue, the concept of polymer networks and protein supramolecular assembly is employed to design artificial protein polymers capable of self-assembly and the formation of well-organized networks. Streptavidin (SAv), a thermally stable tetramer, is chosen as a novel crosslinking mechanism in the protein polymer network due to its ability to self-assemble with high specificity and its crosslinking functionality of at least three. By incorporating SAv monomers into an artificial protein polymer, the self-assembly of SAv-based hydrogels can be achieved. We are the first to demonstrate the use of SAv tetramers as a mechanically stable, crosslinking mechanism in polymer networks for hydrogel fabrication. Furthermore, we uncovered important design principles for mechanically enhancing the SAv tetramer cross-linkers by using its ligand, biotin, and further improving the overall mechanical properties of SAv-crosslinked hydrogels. These findings elucidate the ability to control and tailor the mechanical properties of biomaterials using protein-ligand interactions. This dissertation establishes the groundwork for further advancements in protein-based biomaterials, paving the way for the development of innovative solutions in the field of tissue scaffold technology.