Synthetic polypeptide-based hydrogel systems for biomaterials

Abstract

Hydrogels formed from synthetic polypeptides generated by ring opening polymerization (ROP) of a-amino acid N-carboxyanhydrides (NCAs) present a robust material for modeling the interaction between extracellular matrix (ECM) properties and cellular phenomena. The unique properties of the polypeptide backbone allow it to fold into secondary structures and the ability to modify the side chain presents the opportunity to display chemical functionalities that dictate cellular signaling. The ability to induce cells to form tissue is a chemical and engineering challenge due to the fact that cells need physical support in the form of a 3D scaffold with both chemical and mechanical signals. The Hammond group previously reported the combination of synthetic polypeptides with modified side chains available for click chemistry at quantitative grafting efficiencies. Herein, new schemes for hydrolytically stable versions of the polymer system with click functionality are introduced. Additionally, a new random copolymer, poly(y-propargyl-L-glutamate-co-[gamma]-allyl-L-glutamate) (PPALG) is presented that exploits both the azide-alkyne and thiol-ene click reactions to allow orthogonal side chain modification to increase chemical complexity and ultimately allow a library of "designer" gel systems to be generated.