Silk nanofiber hydrogels with tunable modulus to regulate nerve stem cell fate

Abstract: Reconstruction of damaged nerves remains a significant  unmet challenge in clinical medicine. To foster improvements, the  control of neural stem cell (NSC) behaviors, including migration,  proliferation and

differentiation, is a critical factor to consider. Topographical  and mechanical stimulations based on the control of biomaterial features  are promising approaches, which are usually studied separately. The  synergy between topography and mechanical rigidity could offer new  insights into the control of neural cell fate if they could be utilized  concurrently in studies. To achieve this need, silk fibroin  self-assembled nanofibers with a beta-sheet-enriched structure are  formed into hydrogels. Stiffness is tuned using different annealing  processes to enable mechanical control without impacting the nanofiber  topography. Compared with  onannealed nanofibers, NSCs on methanol  annealed nanofibers with stiffness similar to that of nerve tissues  differentiate into neurons with the restraint of glial differentiation,  without the influence of specific differentiation biochemical factors.  These results demonstrate that combining topographic and mechanical cues  provides the control of nerve cell behaviors, with potential for  neurogenerative repair strategies.