Cooperative assembly of a designer peptide and silk fibroin into hybrid nanofiber gels for neural regeneration after spinal cord injury

Local reconstruction of a permissive environment with biomaterials is a promising strategy to treat spinal cord injury (SCI). We reported a hybrid hydrogel fabricated from a small functional self-assembling peptide (F-SAP) and large silk fibroin (SF). The diffusion of SF micelles into F-SAP solution was driven by the dynamic synergy between osmotic pressure and F-SAP/SF electrostatic interactions, resulting in the rearrangement of SF micelles and the formation of rod-like filaments with axes nearly perpendicular to F-SAP nanofibers. Spectroscopy analysis, including circular dichroism, Raman and fluorescence, indicated conformation changes of SF from random coil to β sheet, which contributed to enhanced mechanical properties of the resultant hybrid hydrogel. Furthermore, the F-SAP/SF hybrid hydrogel coupled with controlled release of NT-3 provided a permissive environment for neural regeneration by providing nanofibrous substrates for regenerating axons, inflammatory modulation and remyelination, consequently resulting in improved locomotion and electrophysiological properties. This hydrogel could be used as a long-term stent in vivo for the treatment of SCI.