3D printing of Y-27632 enhanced elastic hydrogel conduits for peripheral nerve repair

Nerve guide conduits provide an advanced tool for peripheral nerve repair, but their efficacy remains limited due to suboptimal axon regeneration. Y-27632, a ROCK inhibitor, has the potential to promote axon regeneration and functional restoration. Here, we show a Y-27632 enhanced elastic hydrogel conduit for effective nerve repair. The conduit comprised of gelatin methacryloyl (GelMA)/silk fibroin methacryloyl (SF-MA) hydrogels with Y-27632 loaded poly(lactic-co-glycolic acid) (PLGA)/polyvinyl alcohol (PVA) nanoparticles, is rapidly fabricated by a continuous 3D printing process. The drug Y-27632 can be sustainedly released from the conduits to promote neurite elongation. Meanwhile, the bioactive gelatin/fibroin hydrogels can facilitate Schwann cell adhesion, proliferation, and migration. Moreover, the elastic hydrogel conduit can be surgically sutured with nerve stumps to bridge nerve defects. At 16 weeks post-surgery, this conduit efficiently promotes axon regeneration and remyelination, facilitates muscle re-innervation, and enhances functional recovery in a 12 mm nerve defect model. These findings implicate that elastic hydrogel conduits with Y-27632 release would provide a promising therapeutic strategy for long-gap peripheral nerve defects.