Biomineralized silk fibroin hydrogel with ultra-high strength for supporting bodyweight-bearing bone defects.

With four levels of formations and functional properties similar to biological tissues, protein hydrogel attracts great attention from researchers and clinical practitioners for broad applications. However, hydrogels with high water content usually exhibit poor mechanical properties, which limit their widespread application. In the study, a general and feasible approach was used to enhance the regenerated silk fibroin (RSF) hydrogel's mechanical strength by mimicking the human skeleton biomineralization process in vitro. The final mechanical strength was around 4.5 MPa, and the compressive modulus was around 0.90 MPa after combining the effects of ethanol induction of β-sheet and mineralization by SBF, reaching 3 times higher strength than the original RSF hydrogel. The mineral composition and chemical structure proved that the biomineralization of HAp apposition within amorphous hydrophilic domains enhanced the mechanical properties of RSF hydrogel. In vivo RSF hydrogel mineralization was observed after subcutaneous implantation in rats. The femoral bone defect model demonstrated that the biomineralized RSF hydrogel maintained the bone structure from collapse in the early phase. In summary, a straightforward method for fabricating high-strength biomineralized RSF hydrogel through a slow-and-low approach, i.e., low SBF concentration and longer immersion time, was developed and is promising for treating bone diseases.