2. Academic Validation
  3. Rapid 3D printing of functional nanoparticle-enhanced conduits for effective nerve repair

Rapid 3D printing of functional nanoparticle-enhanced conduits for effective nerve repair

  • Acta Biomater. 2019 May;90:49-59. doi: 10.1016/j.actbio.2019.03.047.
Jie Tao 1,  Jiumeng Zhang 2,  Ting Du 2,  Xin Xu 2,  Xianming Deng 3,  Shaochen Chen 4,  Jinlu Liu 2,  Yuwen Chen 2,  Xuan Liu 2,  Meimei Xiong 2,  Yi Luo 5,  Hao Cheng 2,  Jian Mao 6,  Ludwig Cardon 7,  Maling Gou 8,  Yuquan Wei 2
Affiliations

Affiliations

  • 1 State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610065, China; School of Materials Science and Engineering, Sichuan University, Chengdu, Sichuan 610065, China.
  • 2 State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610065, China.
  • 3 State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.
  • 4 NanoEngineering Department, University of California, San Diego, USA.
  • 5 Department of Orthopedics, West China Hospital of Sichuan University, Wai Nan Guo Xue Xiang 37#, 610041 Chengdu, Sichuan, China.
  • 6 School of Materials Science and Engineering, Sichuan University, Chengdu, Sichuan 610065, China.
  • 7 Center for Polymer and Material Technologies, Department of Materials, Textiles and Chemical Engineering, Ghent University, Technologiepark 915, Zwijnaarde, Ghent, Belgium.
  • 8 State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610065, China. Electronic address: [email protected].
PMID: 30930306 DOI: 10.1016/j.actbio.2019.03.047
Abstract

Nerve conduits provide an advanced tool for repairing the injured peripheral nerve that often causes disability and mortality. Currently, the efficiency of conduits in repairing peripheral nerve is unsatisfying. Here, we show a functional nanoparticle-enhanced nerve conduit for promoting the regeneration of peripheral nerves. This conduit, which consists of gelatin-methacryloyl (GelMA) hydrogels with drug loaded poly(ethylene glycol)- poly(3-caprolactone) (MPEG-PCL) nanoparticles dispersed in the hydrogel matrix, is rapidly fabricated by a continuous three-dimensional (3D) printing process. While the 3D-printed hydrogel conduit with customized size, shape and structure provides a physical microenvironment for axonal elongation, the nanoparticles sustained release the drug to facilitate the nerve regeneration. The drug, 4-((5,10-dimethyl-6-oxo-6,10-dihydro-5H-pyrimido[5,4-b]thieno[3,2-e][1,4]diazepin-2-yl)amino) benzenesulfonamide, is a Hippo pathway inhibitor with multiple functions including improving the proliferation and migration of Schwann cells and up-regulating Neurotrophic Factors genes. The descried functional nerve conduit efficiently induced the recovery of sciatic injuries in morphology, histopathology and functions in vivo, showing the potential clinical application in peripheral nerve repair. STATEMENTS OF SIGNIFICANCE: Functional nerve conduit provides a promising strategy alternative to autografts. In this work, we rapidly customized a nanoparticle-enhanced conduit by the continuous bioprinting process. This nanoparticle in the conduit can release a Hippo pathway inhibitor to facilitate the nerve regeneration and function restoration. The efficacy of the conduits is comparable to that of autograft, suggesting the potential clinical applications.

Keywords

3D printing; Drug delivery; Hydrogel; Nanoparticles; Peripheral nerve regeneration.

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