Biomimetic 3D-printed scaffolds for spinal cord injury repair
Biomimetic 3D-printed scaffolds for spinal cord injury repair
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DOI：
10.1038/s41591-018-0296-z
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发表时间：
2019-02-01
期刊：
影响因子：
82.9
通讯作者：
Tuszynski, Mark H.
中科院分区：
文献类型：
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作者：
Koffler, Jacob;Zhu, Wei;Tuszynski, Mark H.
当前的生物打印功能组织的方法缺乏适当的生物制造技术来构建复杂的3D微体系结构，这对于指导细胞生长和促进组织成熟至关重要（1）。中枢神经系统（CNS）结构的3D打印可能由于中枢神经系统架构的复杂性而没有完成。在这里，我们报告使用微观连续投影印刷方法（MU CPP）来创建用于脊髓再生医学应用的复杂CNS结构。 MU CPP可以在1.6 s的尺寸上量身定制的3D仿生水凝胶支架，可扩展到人脊髓大小和病变的几何形状。我们测试了装有神经祖细胞（NPC）支持轴突再生的MU CPP 3D打印支架的能力，并在啮齿动物中体内完全脊髓损伤的部位形成新的“神经继电器”（1,2）。我们发现受伤的宿主轴突将再生为3D仿生型支架，并突触植入了设备中的NPC，并且植入的NPC又将轴突从支架中扩展到骨架中，并在损伤的损伤中延伸到宿主脊髓中，以恢复突触型，并显着提高功能射击。因此，3D仿生支架提供了一种通过精确医学增强CNS再生的方法。
Current methods for bioprinting functional tissue lack appropriate biofabrication techniques to build complex 3D micro-architectures essential for guiding cell growth and promoting tissue maturation(1). 3D printing of central nervous system (CNS) structures has not been accomplished, possibly owing to the complexity of CNS architecture. Here, we report the use of a microscale continuous projection printing method (mu CPP) to create a complex CNS structure for regenerative medicine applications in the spinal cord. mu CPP can print 3D biomimetic hydrogel scaffolds tailored to the dimensions of the rodent spinal cord in 1.6 s and is scalable to human spinal cord sizes and lesion geometries. We tested the ability of mu CPP 3D-printed scaffolds loaded with neural progenitor cells (NPCs) to support axon regeneration and form new 'neural relays' across sites of complete spinal cord injury in vivo in rodents(1,2). We find that injured host axons regenerate into 3D biomimetic scaffolds and synapse onto NPCs implanted into the device and that implanted NPCs in turn extend axons out of the scaffold and into the host spinal cord below the injury to restore synaptic transmission and significantly improve functional outcomes. Thus, 3D biomimetic scaffolds offer a means of enhancing CNS regeneration through precision medicine.