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

  • Biomater Adv. 2025 Dec 26:182:214679. doi: 10.1016/j.bioadv.2025.214679.
Wenbi Wu  1 Haofan Liu  2 Jiamei Zhang  2 Yinchu Dong  2 Min Peng  2 Qi Zhu  2 Yi Zhang  2 Wei Zhao  2 Li Zhang  2 Ya Ren  2 Jinlu Liu  3 Boya Li  2 Wentao Li  2 Yu Hu  4 Jingzhu Duan  5 Maling Gou  6
Affiliations
  • 1. School of Basic Medical Sciences, Chengdu University, Chengdu, China; Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
  • 2. Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
  • 3. Department of Radiation Oncology, Cancer Center, West China hospital of Sichuan University, China.
  • 4. Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan province, China.
  • 5. Department of Orthopaedic Surgery, Shengjing Hospital of China Medical University, Shenyang, 110004, China. Electronic address: [email protected].
  • 6. Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China. Electronic address: [email protected].
Abstract

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.

Keywords
3D printing; Drug nanoparticle; Nerve guide conduit; Peripheral nerve injury.
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