Graphene oxide-PLGA hybrid nanofibres for the local delivery of IGF-1 and BDNF in spinal cord repair

Graphene oxide-PLGA hybrid nanofibres for the local delivery of IGF-1 and BDNF in spinal cord repair
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氧化石墨烯-PLGA 混合纳米纤维用于脊髓修复中 IGF-1 和 BDNF 的局部递送

DOI:
10.1080/21691401.2019.1575843
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发表时间:
2019-01-01
影响因子:
5.8
通讯作者:
Yang, Xiaoyu
Yang, Xiaoyu
中科院分区:
工程技术2区
文献类型:
--
作者:
Pan, Su;Qi, Zhiping;Yang, Xiaoyu

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摘要 脊髓损伤(SCI)可导致病变水平以下永久性、严重的功能损伤,仍然是最具挑战性的临床问题之一。随着组织工程技术的发展,SCI的治疗也取得了进展。胰岛素样生长因子1(IGF-1)和脑源性神经营养因子(BDNF)是与神经再生密切相关的生长因子。在这项研究中,IGF-1 和 BDNF 成功固定在可生物降解的氧化石墨烯 (GO) 掺入的 PLGA (PLGA/GO) 电纺纳米纤维上。利用 MTT 测定、免疫荧光、运动功能检测和组织学观察,在体外和体内研究了固定有 IGF-1 和 BDNF 的 PLGA/GO 纳米纤维对神经发生的影响。我们证明,负载 IGF-1 和 BDNF 的 PLGA/GO 纳米纤维不仅可以保护 NSC 免受 H2O2 诱导的氧化应激,而且还可以在体外增强 NSC 增殖和神经元分化。 SCI 动物模型的体内研究表明,固定在 PLGA/GO 纳米纤维上的 IGF-1 和 BDNF 的局部递送可显着改善功能性运动恢复,减少空洞形成并增加损伤部位的神经元数量。我们的研究表明,PLGA/GO 是 IGF-1 和 BDNF 递送的有效载体,并且将 IGF-1 和 BDNF 固定在 PLGA/GO 纳米纤维上作为脊髓损伤应用的神经植入物具有巨大的潜力。
Abstract Spinal cord injury (SCI) can lead to permanent and severe functional impairment below the lesion level and is still one of the most challenging clinical problems. The treatment of SCI has progressed with the development of tissue engineering techniques. Insulin-like growth factor 1 (IGF-1) and brain-derived neurotrophic factor (BDNF) are growth factors closely related to nerve regeneration. In this study, IGF-1 and BDNF were successfully immobilized on biodegradable graphene oxide (GO)-incorporated PLGA (PLGA/GO) electrospun nanofibres. The effect of PLGA/GO nanofibres with immobilized IGF-1 and BDNF on neurogenesis was investigated in vitro and in vivo utilizing MTT assays, immunofluorescence, motor function detection and histology observations. We demonstrated that PLGA/GO nanofibres loaded with IGF-1 and BDNF not only protected NSCs from oxidative stress induced by H2O2 but also enhanced NSC proliferation and neuronal differentiation in vitro. The in vivo study of an SCI animal model demonstrated that local delivery of IGF-1 and BDNF immobilized to PLGA/GO nanofibres significantly improved functional locomotor recovery, reduced cavity formation and increased the number of neurons at the injury site. Our study indicated that PLGA/GO is an effective carrier for IGF-1 and BDNF delivery and that immobilization of IGF-1 and BDNF onto PLGA/GO nanofibres has a great potential as a nerve implant for spinal cord injury applications.