Physically Cross‐Linked Silk Fibroin Hydrogel with Rapid Sol–Gel Transition and Enhanced Mechanical Performance

Abstract It remains a great challenge to fabricate physically cross‐linked silk fibroin (SF) hydrogels with rapid gelation and robust mechanical properties. In this study, a novel SF hydrogel is obtained by synergistically modulating the SF molecular weight (MW) and the freeze‐inducing process, avoiding the use of any exterior additives. First, the effects of MW on the self‐assembly behaviors of SF are investigated under physiological temperature. The results demonstrate that high MW SF derived from papain degumming (PSF) facilitates the sol–gel transition with increasing β‐sheet content, and contributed to the construction of the hierarchical micro‐nanofiber structure. Subsequently, cryo‐concentration treatment is applied to further accelerate the gelation process. The resultant PSF (F‐PSF) exhibits rapid sol–gel transition (within 1 h), a high compressive modulus (54.2 ± 3.7 kPa), and a high storage modulus (up to 247.9 kPa), which are superior to traditional physically cross‐linked SF hydrogels. The relatively low β‐sheet content and dense structure endow the F‐PSF hydrogels with excellent mechanical flexibility, physiological environmental stability, and long‐term mechanical stability. In vitro cellular experiments show that F‐PSF hydrogels are beneficial to cell proliferation and spreading. These attractive features enable the physically cross‐linked SF hydrogels to be promising for tissue engineering and regenerative medicine.