In this report, a novel silk fibroin hydrogel with a reversible sol–gel transition capacity is presented, in which the base material of this reversible hydrogel is hydrophilic silk fibroin (HSF) obtained by immersing a dried regenerated Bombyx mori silk fibroin (SF) condensate in deionized water (DI water) and collecting its lixivium. The resulting HSF sol can exhibit an enhanced sol–gel transition within several hours at suitable temperatures (25–50 °C) without any exterior additive, even at extremely low concentrations (<0.2%, w/v). The HSF gel can perform thixotropic, reversible gel–sol transitions triggered by a facile cycled shear-thinning and resting procedure. Reversible sol–gel transition kinetics analyses and dynamic measurements of the micro-structure transformation during the transition demonstrate that both the β-sheet self-assembling process and metastable hydrogen bonding (H-bond) interactions among these large scale β-sheet aggregates play essential roles in the significant enhancement of the reversible HSF sol–gel transition. Due to the reversible, thixotropic sol–gel transitions and suitable viscoelasticity of its shear-thinning system for matching random sizes/shapes, the HSF system is possibly an alternative injectable hydrogel for applications in 3-dimensional (3D) cell culture and tissue repair in situ.

The present study examines the influence of the hydrophilic–lipophilic environment, mediated by small molecules, on the structural changes in silk protein fibroin. Small molecules mediate the various hydrophilic–lipophilic balances (HLBs) that impact the organisation of silk protein chains. Changes in the silk fibroin structure due to additives are related to the HLB value. At HLB > 10, silk fibroin primarily forms Silk I crystalline structures. Small molecules with HLB < 8.9 primarily induce the formation of Silk II crystalline structures. When 8.9 < HLB < 10, the crystalline structure of silk is related to the content of small molecules. The Silk I structure is primarily formed when the content of small molecules is low, whereas the Silk II structure is formed when the small molecule content is high. The structure of silk fibroin is maintained by regulating the HLB in the fibroin environment. This type of control for the functional design of materials may play a role in fine-tuning the biomaterial properties of silk fibroin protein.

The present study examines the influence of the hydrophilic–lipophilic environment, mediated by small molecules, on the structural changes in silk protein fibroin. Small molecules mediate the various hydrophilic–lipophilic balances (HLBs) that impact the organisation of silk protein chains. Changes in the silk fibroin structure due to additives are related to the HLB value. At HLB > 10, silk fibroin primarily forms Silk I crystalline structures. Small molecules with HLB < 8.9 primarily induce the formation of Silk II crystalline structures. When 8.9 < HLB < 10, the crystalline structure of silk is related to the content of small molecules. The Silk I structure is primarily formed when the content of small molecules is low, whereas the Silk II structure is formed when the small molecule content is high. The structure of silk fibroin is maintained by regulating the HLB in the fibroin environment. This type of control for the functional design of materials may play a role in fine-tuning the biomaterial properties of silk fibroin protein.