Silk-Graphene Hybrid Hydrogels with Multiple Cues to Induce Nerve Cell Behavior

Cell behavior is dependent in part on chemical and physical cues from the extracellular matrix. Although the influence of various cues on cell behavior has been studied, challenges remain to incorporate multiple cues to matrix systems to optimize and control cell outcomes. Here, aligned silk fibroin (SF)-graphene hydrogels with preferable stiffness were developed through arranging SF nanofibers and SF-modified graphene sheets under an electric field. Different signals, such as bioactive graphene, nanofibrous structure, aligned topography, and mechanical stiffness, were tailored into the hydrogel system, providing niches for nerve cell responses. The desired adhesion, proliferation, differentiation, extension and growth factor secretion of multiple nerve-related cells was achieved on these hydrogels, suggesting strong synergistic action through the combination of different cues. Based on the fabrication strategy, our present study provides a useful materials engineering platform for revealing cooperative influences of different signals on nerve cell behavior, to help in the understanding of cell-biomaterial interactions, with potential toward studies related to nerve regeneration.