Adhesive, Stretchable, and Spatiotemporal Delivery Fibrous Hydrogels Harness Endogenous Neural Stem/Progenitor Cells for Spinal Cord Injury Repair

Aligned fibrous hydrogels capable of recruiting endogenous neural stem/progenitor cells (NSPCs) show great promise in spinal cord injury (SCI) repair. However, the hydrogels suffer from severe issues in close contact with the transected nerve stumps and harnessing the NSPC fate in the lesion microenvironment. Herein, we report aligned collagen-fibrin (Col-FB) fibrous hydrogels with stretchable property, adhesive behavior, and stromal cell-derived factor-1α (SDF1α)/paclitaxel (PTX) spatiotemporal delivery capability. The resultant Col-FB fibrous hydrogels exhibited 1.98 times longer elongation at break (230%), 2.55 times lower Young's modulus (17.93 ± 1.16 KPa), and 2.21 times greater adhesive strength (3.45 ± 0.48 KPa) than collagen (Col) fibrous hydrogels. The soft aligned fibrous hydrogels simulate the oriented microstructure and soft tissue feature of a natural spinal cord and provide elasticity and adhesivity to ensure a persistent close contact with host stumps. The repair of complete transection SCI in rats demonstrates that "middle-to-bilateral" SDF1α gradient release induced endogenous NSPC migration to the lesion site in 10 days, and SDF1α/PTX sequential release promoted neuronal differentiation of the recruited NSPCs over 8 weeks, leading to hind limb locomotion recovery. The presented strategy was proved to be efficient for harnessing endogenous NSPCs, which facilitate SCI repair significantly.