Abstract Among varied silk fibroin (SF) materials, chemically crosslinked SF hydrogels (SFHs) showed excellent biocompatibility and ECM-mimetic property, thus been widely used in biomedical applications. Intriguingly, recent studies have uncovered a unique dynamic material cue in SFHs-the protein conformational transition microenvironment. This microenvironment induces a dynamic material stiffening/shrinkage process and further significantly regulates cell behaviors, thus presents another promising dynamic material cue for biomedical applications. Very recently, to enhance the controllability of this microenvironment and elucidate how conformational transition rates influence cell behaviors, novel strategies for regulating the transitions have been developed, leading to deeper insights into the corresponding cell–microenvironment interactions. Focused on this dynamic microenvironment, we seek to comprehensively describe the intrinsic mechanism of the transitions, the dynamic material features induced by the transition and corresponding characterization methods. It also highlights recent findings and advances in the effective regulation strategies, as well as their promising biomedical applications. Finally, current challenges and future prospects regarding the engineering of this unique microenvironment and its potential applications are comprehensively discussed. This review aims to effectively expand the knowledge of dynamic material cues and the related cell-material interactions, and also offering valuable insights for the development of unique SF and other protein-based biomaterials.
Yao et al. (Tue,) studied this question.