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用于神经再生的基于神经细胞外基质和聚乳酸-聚己内酯的电纺双层神经导管。

Nerve ECM and PLA-PCL based electrospun bilayer nerve conduit for nerve regeneration.

作者信息

Mao Xiaoyan, Li Ting, Cheng Junqiu, Tao Meihan, Li Zhiyuan, Ma Yizhan, Javed Rabia, Bao Jie, Liang Fang, Guo Weihong, Tian Xiaohong, Fan Jun, Yu Tianhao, Ao Qiang

机构信息

Department of Tissue Engineering, China Medical University, Shenyang, China.

Department of Laboratory Medicine, Shengjing Hospital of China Medical University, Shenyang, China.

出版信息

Front Bioeng Biotechnol. 2023 Mar 2;11:1103435. doi: 10.3389/fbioe.2023.1103435. eCollection 2023.

Abstract

The porcine nerve-derived extracellular matrix (ECM) fabricated as films has good performance in peripheral nerve regeneration. However, when constructed as conduits to bridge nerve defects, ECM lacks sufficient mechanical strength. In this study, a novel electrospun bilayer-structured nerve conduit (BNC) with outer poly (L-lactic acid-co-ε-caprolactone) (PLA-PCL) and inner ECM was fabricated for nerve regeneration. The composition, structure, and mechanical strength of BNC were characterized. Then BNC biosafety was evaluated by cytotoxicity, subcutaneous implantation, and cell affinity tests. Furthermore, BNC was used to bridge 10-mm rat sciatic nerve defect, and nerve functional recovery was assessed by walking track, electrophysiology, and histomorphology analyses. Our results demonstrate that BNC has a network of nanofibers and retains some bioactive molecules, including collagen I, collagen IV, laminin, fibronectin, glycosaminoglycans, nerve growth factor, and brain-derived neurotrophic factor. Biomechanical analysis proves that PLA-PCL improves the BNC mechanical properties, compared with single ECM conduit (ENC). The functional evaluation of results indicated that BNC is more effective in nerve regeneration than PLA-PCL conduit or ENC. In conclusion, BNC not only retains the good biocompatibility and bioactivity of ECM, but also obtains the appropriate mechanical strength from PLA-PCL, which has great potential for clinical repair of nerve defects.

摘要

制成薄膜的猪神经源性细胞外基质(ECM)在周围神经再生方面具有良好性能。然而,当构建成用于桥接神经缺损的导管时,ECM缺乏足够的机械强度。在本研究中,制备了一种新型的具有外层聚(L-乳酸-共-ε-己内酯)(PLA-PCL)和内层ECM的电纺双层结构神经导管(BNC)用于神经再生。对BNC的组成、结构和机械强度进行了表征。然后通过细胞毒性、皮下植入和细胞亲和力试验评估BNC的生物安全性。此外,使用BNC桥接10毫米大鼠坐骨神经缺损,并通过行走轨迹、电生理学和组织形态学分析评估神经功能恢复情况。我们的结果表明,BNC具有纳米纤维网络,并保留了一些生物活性分子,包括I型胶原、IV型胶原、层粘连蛋白、纤连蛋白、糖胺聚糖、神经生长因子和脑源性神经营养因子。生物力学分析证明,与单一ECM导管(ENC)相比,PLA-PCL改善了BNC的机械性能。结果的功能评估表明,BNC在神经再生方面比PLA-PCL导管或ENC更有效。总之,BNC不仅保留了ECM良好的生物相容性和生物活性,还从PLA-PCL获得了合适的机械强度,在神经缺损的临床修复方面具有巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3952/10017983/24adcfc41df9/fbioe-11-1103435-g001.jpg

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