A Universal and Facile Approach for the Formation of a Protein Hydrogel for 3D Cell Encapsulation

A universal and facile approach to modifying proteins so that they can rapidly form hydrogel upon mixing with crosslinkers is presented. The concept of it is to introduce maleimide, which is highly reactive with dithiol‐containing crosslinkers via thiol‐ene click chemistry, onto proteins. Bovine serum albumin (BSA) is used as a model protein due to its good stability and low cost. The results here show that a protein hydrogel can be readily formed by blending modified BSA and resilin‐related peptide crosslinker solutions at a proper ratio. The hydrogel exhibits good elasticity and tunable mechanical as well as biochemical properties. Moreover, it allows convenient 3D cell encapsulation and shows good biocompatibility. Muscle cells embedded in the hydrogel are promoted to spread by incorporating arginyl‐glycyl‐aspartic acid (RGD)‐containing peptide into the system, thus warranting a bright future of it in regenerative medicine. A universal and facile approach for the formation of a protein hydrogel is presented. The concept is to introduce maleimide, which is highly reactive with dithiol‐containing crosslinkers, onto proteins. Bovine serum albumin is used as a model protein and a resilin‐related peptide is used as the crosslinker. The fabricated hydrogel shows good biocompatibility and can promote cell spreading and growth by incorporating an RGD ligand.