The “Inner–Outer” Molecules-Loaded Fiber-Hydrogel Scaffolds Coordinate Specific Immunity and Neural Differentiation for Repairing SCI

The treatment of spinal cord injury (SCI) remains unsatisfactory because of the inflammatory microenvironment and the limited potential for nerve regeneration. However, most treatments have focused on modulating nonspecific immunity and ignored the importance of specific immunity in SCI. In this study, an “Inner–Outer” Metformin (Met) and anti-CD80 monoclonal antibody (CD80 mAb)-loaded fiber-hydrogel scaffold (P/G-Met-CD80 mAb) was constructed through microsol-electrospinning and UV illumination methods. The P/G-Met-CD80 mAb scaffolds exhibited good biocompatibility and hydrophilicity, facilitating cell proliferation and adhesion. In addition, the scaffolds were capable of releasing CD80 mAb and Met sequentially, exerting their protected functions at different stages post-SCI in rats. The released CD80 mAb at an early stage significantly inhibited specific immune response by blocking T-cell costimulatory activation and reducing IL-2 secretion, improving the inflammatory microenvironment after SCI. Late stage-released Met recruited neural stem cells (NSCs) to the injury area and enhanced NSCs differentiation into neurons. The P/G-Met-CD80 mAb scaffolds with specific immunomodulatory functions and neurogenic potential provide a new strategy for repairing SCI in the clinic.