Institute of Polymer Science and Engineering, National Taiwan University, Taipei, Taiwan, Republic of China.
Department of Life Science, National Taiwan University, Taipei, Taiwan, Republic of China.
ACS Biomater Sci Eng. 2020 Jan 13;6(1):597-609. doi: 10.1021/acsbiomaterials.9b01473. Epub 2019 Dec 2.
Graphene, with excellent conductivity can promote the growth and differentiation of neural stem cells (NSCs), but the rigidity has limited its direct application in neural tissue engineering. In this study, waterborne biodegradable polyurethane (PU) was used as the matrix for the graphene nanocomposite materials to make graphene applicable to biocompatible scaffolds. The graphene sheets were observed on the surface of the composites which contained 5 wt % graphene (PU-G5). The nanocomposite retained the positive effect of graphene on cell behavior, while PU was flexible enough for further fabrication. Endothelial cells (ECs) and NSCs cocultured on the nanocomposite became more vascular-like and glial-like without induction culture medium. The specific vascular-related and neural-related gene markers, KDR, VE-Cadherin, and GFAP, were upregulated more than twice as the content of graphene increased (5 wt %). The fibrous capsule of the PU-G5 film group was about 38 μm in thickness in subcutaneous implantation, which was only half that of the graphene-free group. Nerve conduits made of the PU-graphene nanocomposite were found to promote the regeneration of the peripheral nerve in a rat sciatic nerve 10 mm gap transection model. In particular, the regenerated tissue in PU-G5 conduits showed an obvious response peak in the compound action potential (CAP) examination and had a similar CAP wave pattern to that of the normal sciatic nerve. However, such a response was not observed in the PU group. The nerve conduit made of PU-G5 had 72% and 50% enhancement on the numbers of axons and blood vessels of regenerated tissue, respectively. The regenerated area of nerve in PU-G5 was 25% larger than that in pristine PU. Compared with the U.S. Food and Drug Administration (FDA) approved conduit, Neurotube, the regenerated nerve in PU-G5 was 1.7 times more than that in Neurotube. In addition to the fast recovery rate, the ability to regenerate tissue with normal morphology is a significant finding of this study that may lead to clinical applications in the future. PU-graphene nanocomposites thus have potential applications in neural tissue engineering.
石墨烯具有优异的导电性，能促进神经干细胞（NSCs）的生长和分化，但由于其刚性，限制了其在神经组织工程中的直接应用。在本研究中，水基可生物降解的聚氨酯（PU）被用作石墨烯纳米复合材料的基质，以使石墨烯适用于生物相容性支架。在含有 5wt%石墨烯的复合材料（PU-G5）表面观察到石墨烯片。纳米复合材料保留了石墨烯对细胞行为的积极作用，同时 PU 又足够柔软，可进一步加工。未经诱导培养基培养，内皮细胞（ECs）和 NSCs 在纳米复合材料上共培养后，更具血管样和神经胶质样。随着石墨烯含量的增加（5wt%），特定的血管相关和神经相关基因标志物 KDR、VE-Cadherin 和 GFAP 的上调超过两倍。在皮下植入时，PU-G5 膜组的纤维囊厚度约为 38μm，仅为无石墨烯组的一半。在大鼠坐骨神经 10mm 间隙横断模型中，发现由 PU-石墨烯纳米复合材料制成的神经导管能促进周围神经的再生。特别是，在 PU-G5 导管中再生组织的复合动作电位（CAP）检查中显示出明显的反应峰，并且具有与正常坐骨神经相似的 CAP 波模式。然而，在 PU 组中没有观察到这种反应。与美国食品和药物管理局（FDA）批准的导管 Neurotube 相比，PU-G5 制成的神经导管分别使再生组织中的轴突和血管数量增加了 72%和 50%。在 PU-G5 中，神经再生区比原始 PU 大 25%。与 FDA 批准的导管 Neurotube 相比，PU-G5 中的再生神经是 Neurotube 的 1.7 倍。除了快速的恢复率之外，能够再生具有正常形态的组织是本研究的一个重要发现，这可能导致未来的临床应用。因此，PU-石墨烯纳米复合材料在神经组织工程中有潜在的应用。
