Abstract
Spinal cord injury (SCI) leads to massive cell death, disruption, and demyelination of axons, resulting in permanent motor and sensory dysfunctions. Stem cell transplantation is a promising therapy for SCI. However, owing to the poor microenvironment that develops following SCI, the bioactivities of these grafted stem cells are limited. Cell implantation combined with biomaterial therapies is widely studied for the development of tissue engineering technology. Herein, an insulin-like growth factor-1 (IGF-1)-bioactive supramolecular nanofiber hydrogel (IGF-1 gel) is synthesized that can activate IGF-1 downstream signaling, prevent the apoptosis of neural stem cells (NSCs), improve their proliferation, and induce their differentiation into neurons and oligodendrocytes. Moreover, implantation of NSCs carried out with IGF-1 gels promotes neurite outgrowth and myelin sheath regeneration at lesion sites following SCI. In addition, IGF-1 gels can enrich extracellular vesicles (EVs) derived from NSCs or from nerve cells differentiated from these NSCs via miRNAs related to axonal regeneration and remyelination, even in an inflammatory environment. These EVs are taken up by autologous endogenous NSCs and regulate their differentiation. This study provides adequate evidence that combined treatment with NSCs and IGF-1 gels is a potential therapeutic strategy for treating SCI.