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具有按需工程化灰质和白质的3D纳米纤维框架用于重建受损脊髓。

3D nanofibrous frameworks with on-demand engineered gray and white matters for reconstructing the injured spinal cord.

作者信息

Girão André F, Barroca Nathalie, Hernández-Martín Yasmina, Completo António, Marques Paula A A P, Serrano María C

机构信息

Center for Mechanical Technology and Automation (TEMA), Department of Mechanical Engineering, University of Aveiro (UA), Aveiro 3810-193, Portugal; Instituto de Ciencia de Materiales de Madrid (ICMM), Consejo Superior de Investigaciones Científicas (CSIC), Calle Sor Juana Inés de la Cruz 3, Madrid 28049, Spain.

Center for Mechanical Technology and Automation (TEMA), Department of Mechanical Engineering, University of Aveiro (UA), Aveiro 3810-193, Portugal.

出版信息

Biomater Adv. 2025 May;170:214200. doi: 10.1016/j.bioadv.2025.214200. Epub 2025 Jan 30.

DOI:10.1016/j.bioadv.2025.214200
PMID:39904017
Abstract

Spinal cord injury (SCI) is a disruptive and heterogeneous medical condition affecting millions of patients worldwide. Due to the absence of medical treatments to effectively restore the lost sensorimotor and autonomic functions, there is an ongoing pursuit of scaffolds aiming to bridge the injured spinal area. Herein, a novel electrospinning modality to construct 3D nanofibrous frameworks (NFFs) in accordance with distinct spinal cord microenvironments is used to engineer a biomimetic hemicord. This scaffolding concept gravitates around the possibility of customizing NFFs with on-demand engineered gray and white matters to replicate the native spinal cytoarchitecture. In particular, a 3D reduced graphene oxide-based fibrous-porous system is developed to imitate the gray matter, while a 3D polycaprolactone (PCL)-chitosan nanofibrous network combined with PCL-graphene microfibers intends to mimic the white matter. The scaffolding components are tested in vitro with embryonic neural progenitor cells, integrated into the biomimetic NFF, and then tested in vivo in paralyzed rats with cervical hemisection. After 4 months of implantation, the scaffold generates both neuroprotective (e.g., limited infiltration of vimentin and ED1 cells) and neuroregenerative (e.g., presence of new blood vessels and neurites) features accompanied with promising signs of forelimb function recovery.

摘要

脊髓损伤(SCI)是一种破坏性且异质性的医学病症,影响着全球数百万患者。由于缺乏有效恢复丧失的感觉运动和自主功能的医学治疗方法,人们一直在寻求旨在桥接受损脊髓区域的支架。在此,一种根据不同脊髓微环境构建三维纳米纤维框架(NFFs)的新型静电纺丝方式被用于构建仿生半脊髓。这种支架概念围绕着通过按需设计灰质和白质来定制NFFs以复制天然脊髓细胞结构的可能性展开。具体而言,开发了一种基于三维还原氧化石墨烯的纤维多孔系统来模仿灰质,而一种结合了聚己内酯(PCL)-石墨烯微纤维的三维聚己内酯(PCL)-壳聚糖纳米纤维网络旨在模拟白质。支架组件在体外与胚胎神经祖细胞进行测试,整合到仿生NFF中,然后在患有颈髓半切的瘫痪大鼠体内进行测试。植入4个月后,支架产生了神经保护(例如波形蛋白和ED1细胞的有限浸润)和神经再生(例如新血管和神经突的存在)特征,并伴有前肢功能恢复的良好迹象。

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