Aligned Graphene Mesh-Supported Double Network Natural Hydrogel Conduit Loaded with Netrin-1 for Peripheral Nerve Regeneration
Aligned Graphene Mesh-Supported Double Network Natural Hydrogel Conduit Loaded with Netrin-1 for Peripheral Nerve Regeneration
复制标题
加载 Netrin-1 的对齐石墨烯网支撑双网络天然水凝胶导管，用于周围神经再生
DOI：
10.1021/acsami.0c16391
复制
发表时间：
2021-01-05
影响因子：
9.5
通讯作者：
Lu, Xinwu
中科院分区：
文献类型：
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作者：
Huang, Qun;Cai, Yuting;Lu, Xinwu
周围神经损伤（PNI）的金标准治疗是自体移植，但它与供体短缺有关，并导致严重的并发症。在本研究中，我们设计了一种石墨烯网格支撑的双网络（DN）水凝胶支架，负载netrin-1。通过快速离子交换和紫外线照射合成的天然藻酸盐和明胶-甲基丙烯酰缠结水凝胶提供适当的机械强度和优异的生物相容性，并且还可以作为netrin-1的储库。同时，石墨烯网可以促进雪旺细胞的增殖并引导其排列。这种方法允许支架具有可接受的杨氏模量725.8 +/- 46.52 kPa，与周围神经匹配，以及令人满意的电导率6.8 +/- 0.85 S/m。此外，netrin-1在引导轴突寻路和神经元迁移方面发挥双重作用，在100 ng/mL的浓度下优化了管形成能力。这种负载netrin-1的石墨烯网状管/DN水凝胶神经支架能够显著促进周围神经的再生和失神经肌肉的恢复，甚至上级优于自体移植物。我们的研究结果可能为PNI患者提供一种有效的治疗策略，可以取代稀缺的自体移植物。
The gold standard treatment for peripheral nerve injuries (PNIs) is the autologous graft, while it is associated with the shortage of donors and results in major complications. In the present study, we engineer a graphene mesh-supported double-network (DN) hydrogel scaffold, loaded with netrin-1. Natural alginate and gelatin-methacryloyl entangled hydrogel that is synthesized via fast exchange of ions and ultraviolet irradiation provide proper mechanical strength and excellent biocompatibility and can also serve as a reservoir for netrin-1. Meanwhile, the graphene mesh can promote the proliferation of Schwann cells and guide their alignments. This approach allows scaffolds to have an acceptable Young's modulus of 725.8 +/- 46.52 kPa, matching with peripheral nerves, as well as a satisfactory electrical conductivity of 6.8 +/- 0.85 S/m. In addition, netrin-1 plays a dual role in directing axon pathfinding and neuronal migration that optimizes the tube formation ability at a concentration of 100 ng/mL. This netrin-1-loaded graphene mesh tube/DN hydrogel nerve scaffold can significantly promote the regeneration of peripheral nerves and the restoration of denervated muscle, which is even superior to autologous grafts. Our findings may provide an effective therapeutic strategy for PNI patients that can replace the scarce autologous graft.