Viscoelastic Silk Fibroin Hydrogels with Tunable Strength

Hydrogels are often used as synthetic extracellular matrices (ECMs) for biomedical applications. Natural ECMs are viscoelastic and exhibit partial stress relaxation. However, commonly used hydrogels are typically elastic. Hydrogels developed from ECM-based proteins are viscoelastic, but they often have weak mechanical properties. Here, biocompatible viscoelastic hydrogels with excellent mechanical performance are fabricated by an all aqueous process at body or room temperature. These hydrogels offer obvious stress relaxation and tunable mechanical properties and gelation kinetics. Their compressive modulus can be controlled between 2 kPa and 1.2 MPa, covering a significant portion of the properties of native tissues. Investigation of the gelation mechanism revealed that silk fibroin gelation is caused by the synergistic effects of hydrophobic interaction and hydrogen bonding between silk fibroin molecules. Newly formed crystals serve as the cross-link sites and form a network endowing the hydrogel with stable structure, and the flexible noncrystalline silk nanofibers connect disparate silk fibroin crystals, endowing hydrogels with viscoelastic properties. The all aqueous gelation process avoids complex chemical and physical treatments and is beneficial for encapsulating cells or biomolecules. Encapsulation of chondrocytes results in high initial survival rate (95% ± 1%). These silk fibroin-based viscoelastic hydrogels, combined with superior biocompatible and tunable mechanical properties, represent an exciting option for tissue engineering and regenerative medicine.