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.
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610065, China.
Acta Biomater. 2019 May;90:49-59. doi: 10.1016/j.actbio.2019.03.047. Epub 2019 Mar 28.
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.
神经导管为修复受损外周神经提供了一种先进的工具，外周神经损伤常常导致残疾和死亡。目前，导管在外周神经修复中的效率并不令人满意。在这里，我们展示了一种功能性纳米粒子增强神经导管，用于促进周围神经的再生。这种导管由载药的聚乙二醇-聚（3-己内酯）（MPEG-PCL）纳米粒子分散在水凝胶基质中的明胶甲基丙烯酰（GelMA）水凝胶组成，通过连续的三维（3D）打印工艺快速制造。虽然具有定制尺寸、形状和结构的 3D 打印水凝胶导管为轴突伸长提供了物理微环境，但纳米粒子持续释放药物有助于神经再生。该药物 4-((5,10-二甲基-6-氧代-6,10-二氢-5H-嘧啶并[5,4-b]噻吩并[3,2-e][1,4]二氮嗪-2-基)氨基)苯磺酰胺是一种 Hippo 通路抑制剂，具有多种功能，包括提高施万细胞的增殖和迁移能力，并上调神经营养因子基因。所描述的功能性神经导管在体内形态、组织病理学和功能上有效地促进了坐骨神经损伤的恢复，显示出在外周神经修复中的潜在临床应用。
功能性神经导管为自体移植物提供了一种有前途的替代方案。在这项工作中，我们通过连续的生物打印工艺快速定制了一种纳米粒子增强导管。导管中的纳米粒子可以释放 Hippo 通路抑制剂，以促进神经再生和功能恢复。导管的疗效可与自体移植物相媲美，表明其具有潜在的临床应用。
