Autonomous Self-Healing Silk Fibroin Injectable Hydrogels Formed via Surfactant-Free Hydrophobic Association

Many natural materials, such as silk, animal bone, nacre, and plant fibers, achieve outstanding strength and toughness through the rupture of sacrificial bonds between chain segments in the organic phase. In this work, we present a bioinspired strategy to fabricate silk fibroin-based hydrophobic-association (HA) hydrogels by incorporating the hydrophobic interaction as a sacrificial bond into the alginate ionic network, which not only enhanced the mechanical extensibility, strength, and toughness of the hydrogels but also enabled self-recovery and self-healing properties via reversible hydrophobic interactions without external stimuli at room temperature. The hydrophobic interaction system consisted of the hydrophobic monomer stearyl methacrylate (C18M) and an amphiphilic regenerated silk fibroin (RSF) solution. The mechanical tests and rheometry indicated that the hydrophobic interaction served as the sacrificial bond that preferentially ruptures prior to the alginate ionic network under an external load, which dissipated enormous amounts of energy and conferred an improved mechanical performance. Moreover, the structure of HA gels could be quickly recovered after injection due to the existence of hydrophobic interactions. In addition, the degradability of the HA gels in a protease XIV solution was strongly dependent upon the C18M component, which significantly promoted the degradation rate of HA gels. The biomimetic mineralization process of HA gels within a simulated body fluid (SBF), mimicking the inorganic composition of human blood plasma, was performed and the calcium phosphate nanoparticles on the hydrogel were observed. Importantly, in vivo experiments illustrated that the HA gels exhibited satisfactory biocompatibility, and the mouse osteoblasts (MC3T3-E1) could attach and spread on the hydrogels. Overall, the self-healing, biocompatibility, and high mechanical properties of the HA gels render them potentially suitable for load-bearing applications in drug delivery or other soft tissue-engineering applications.