Birefringent Silk Fibroin Hydrogel Constructed via\nBinary Solvent-Exchange-Induced Self-Assembly

Abstract

Birefringent\nhydrogels have a strong potential for applications\nin biomedicine and optics as they can modulate the optical and mechanical\nanisotropy in confined two-dimensional geometries. However, production\nof birefringent hydrogels with hierarchical structures, mechanical\nproperties, and biorelated behavior that are analogous to biological\ntissues is still challenging. Starting from the silk fibroin (SF)-ionic\nliquid solution system, this study aimed to rationally design a “binary\nsolvent-exchange-induced self-assembly (BSEISA)” strategy to\nproduce birefringent SF hydrogels (SFHs). In this method, the conformational\ntransition rate of SF can be effectively controlled by the exchange\nrate of the binary solvents. Therefore, this method provides the possibility\nof controlling the conformation and orientation of SF. Molecular simulations\nconfirmed that methanol is more effective in driving β-sheet\nformation than other often used solvents, such as formic acid and\nwater. The formed β-sheets act as the physical cross-links that\nconnect disparate protein chains, thereby forming continuous and stable\nthree-dimensional (3D) hydrogel networks. The resultant BSEISA-SFHs\nare transparent and birefringent with mechanical characteristics similar\nto those of soft biological tissues, such as lens and cartilage. Interestingly,\nour results revealed that the evolution of experimental birefringent\nfringes perfectly matched the changes in stress distribution predicted\nusing finite element analysis. Owing to the unique birefringence of\nBSEISA-SFHs, together with the advantages in mechanical performance,\nthese hydrogels are anticipated to act as good tissue surrogates for\nunderstanding the mechanical response of biological tissues.