title: 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 are critical factors to consider. Topographical and mechanical stimulation based on the control of biomaterial features is a promising approach, 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 nonannealed nanofibers, NSCs on methanol annealed nanofibers with stiffness similar to 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.
authors.affiliation: National Engineering Laboratory for Modern Silk & Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou 215123, People's Republic of China.
authors.forename: ShuMeng
authors.initials: S
authors.lastname: Bai
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, the Second Affiliated Hospital, Soochow University, Suzhou 215123, People's Republic of China.
authors.forename: WenMin
authors.initials: W
authors.lastname: Zhang
authors.affiliation: National Engineering Laboratory for Modern Silk & Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou 215123, People's Republic of China ; Jiangsu Province Key Laboratory of Stem Cell Research, Medical College, Soochow University, Suzhou 215006, People's Republic of China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, the Second Affiliated Hospital, Soochow University, Suzhou 215123, People's Republic of China.
authors.forename: QuanHong
authors.initials: Q
authors.lastname: Ma
authors.affiliation: National Engineering Laboratory for Modern Silk & Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou 215123, People's Republic of China ; Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Kaplan
authors.affiliation: Research Center of Materials Science, Beijing Institute of Technology, Beijing, 100081, People's Republic of China.
authors.forename: HeSun
authors.initials: H
authors.lastname: Zhu
keywords: hydrogels; nerve regeneration; neural stem cells; silk nanofibers; tunable stiffness