Soft freezing-induced self-assembly of silk fibroin for tunable gelation

Silk fibroin (SF) hydrogel is a promising candidate in biomaterial field; however its application is quite limited by long-gelation time. In the present study, we developed a novel strategy named soft freezing to accelerate the process and control the sol-gel transition of SF protein. SF protein was induced to self-assembly by soft freezing process for achieving the reconstructed SF solution with metastable structure. It was found that the soft freezing process triggers the structural transition from random structure to ordered structure-rich conformation. Gelation kinetics showed that the gelation time of SF protein could be regulated by changing freezing time and initial concentration. The reconstructed SF solution allowed enhanced sol-gel transition within 6 hours, even at extremely low concentration. The attractive features of the method described here include the accelerated gelation, free of chemical agents, and reducing processing complexity. The SF solution with short gelation time will be applicable as cell encapsulation and injectable applications for tissue engineering and regenerative medicine, which greatly expand the applications of SF hydrogels.