(569f) Engineering Click-Protein Hydrogel for Tissue Engineering

Protein-based hydrogels have many advantages over synthetic hydrogels for diverse applications owing to the many intrinsic properties of the proteins such as bio-compatibility, innocuousness, and biological activity. In addition, the ability of proteins to form self-organized, uniform and regulated structure with precise control facilitates the synthesis of hydrogel with the desired properties. However, strategies for protein hydrogel synthesis remain limited, leaving the field of protein hydrogel largely underdeveloped.
In this study, we present a robust, convenient and efficient click-hydrogel strategy that enables any protein to be transformed into bioactive protein hydrogels. This strategy is based on the copper-free click chemistry reaction that is highly efficient, stereo-specific and bio-orthogonal. The target proteins are first separately labelled with a desired functional group. Mixing of functionalized proteins under physiological condition leads to the spontaneous formation of a highly cross-linked protein network or hydrogel through click reaction.
Here, we demonstrate our click-hydrogel strategy using various target proteins of different sizes and quaternary structures. The mechanical properties of the hydrogel are affected by the protein concentration, quaternary structure and the density of the functional group. Protein hydrogels with compressive modulus from 2kPa to 200kPa, high stability in aqueous solution and high porosity were successfully synthesized. In addition, our click-hydrogels exhibit shape-memory properties and dehydrated hydrogels are able to completely and rapidly regain their original shape upon rehydration. Hydrogels made from proteins containing integrin-binding motif (RGD) are able to efficiently support mammalian cells attachment and proliferation with little to no toxicity. Our click-protein hydrogel should have broad application in biomaterial, tissue and biofuel cell engineering.