Physically Cross-Linked Silk Hydrogels with High Solid Content and Excellent Mechanical Properties via a Reverse Dialysis Concentrated Procedure

Silk fibroin (SF) based hydrogels are the focus of extensive research due to their ability to form complex hierarchical structures, as well as their biocompatibility and biodegradability. However, the weak mechanical properties and lengthy gelation time of SF hydrogels limit their practical applications. In this paper, we developed a facile yet effective strategy, reverse dialysis against PEG, to produce tough SF composite hydrogels that were completely cross-linked by hydrogen bonds. This was achieved by the addition of polyethylene glycol (PEG) and hydroxyl propyl methyl cellulose (HPMC) that served as cross-linker and reinforcing phase, respectively, which avoided using chemical cross-links that were unfavorable for biocompatibility. The uniaxial deformation tests demonstrated that the obtained SF ternary hydrogel (SF-PEG-HPMC) exhibited excellent mechanical performances with a Young's modulus and fracture stress attained up to 91 and 6.71 MPa, respectively, which were superior to the previously reported SF-based hydrogels. Besides, the ternary hydrogels showed significant extensibility (219%) at a unique high solid content (48.89 wt %) that resulted in high toughness (1 MJ/m3). Intriguingly, the SF chains could align along the stress direction, where the oriented hierarchical structures were formed and thus increased the fracture stress of prestretched hydrogels. Moreover, the mechanical properties of SF hydrogels could be further improved by immersion in ammonium sulfate solution which contributed to expanding their applications as structural materials. The elucidation of the mechanism of reverse dialysis of SF hydrogels provided a simple approach to prepare a physically cross-linked natural biopolymer with outstanding mechanical properties and paved the way to potentially apply them in the biomedical field.