Neurotrophin-3-Loaded Multichannel Nanofibrous Scaffolds Promoted Anti-Inflammation, Neuronal Differentiation, and Functional Recovery after Spinal Cord Injury

Abstract

The clinical therapeutics for nerve tissue regeneration and functional recovery after spinal cord injury (SCI) are very limited because of the complex biological processes and inhibitory microenvironment. Advanced biomaterials are highly desired to avoid severe secondary damage and provide guidance for axonal regrowth. Multichannel nanofibrous scaffolds were modified with gelatin and cross-linked by genipin. The gelatin-coated nanofibers exhibited strong binding affinity with neurotrophin-3, which underwent a well-controlled release and highly promoted neuronal differentiation and synapse formation of the seeded neural stem cells. The nanofibrous scaffolds fabricated by combinatorial biomaterials were implanted into complete transected spinal cords in rats. Not only were the inflammatory responses and collagen/astrocytic scar formation limited, but the functional neurons and remyelination were facilitated postsurgery, leading to highly improved functional restoration. This nanofibrous scaffold with high specific surface area can be easily modified with biomolecules, which was proven to be effective for nerve regeneration after transected SCI, and provided a springboard for advanced scaffold design in clinical applications.