锂负载电纺纳米纤维支架促进大鼠模型中损伤坐骨神经的轴突再生和功能恢复

IF 8.1 1区 医学 Q1 ENGINEERING, BIOMEDICAL
Banafsheh Dolatyar, Bahman Zeynali, Iman Shabani, Azita Parvaneh Tafreshi, Reza Karimi-Soflou
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引用次数: 0

摘要

越来越多的证据表明,工程神经移植物在周围神经损伤(PNIs)再生方面具有巨大潜力。大多数研究只关注移植物的地形特征,而我们的应用纳米支架则同时考虑了生物物理和生物化学操作。为此,我们制作了一种电纺纳米纤维支架(ENS),其中含有负载锂(Li)离子(一种 Wnt/β-catenin 信号激活剂)的聚乳酸纳米纤维。此外,我们还将人脂肪间充质干细胞(hADMSCs)播种到这种工程支架上,以研究是否能诱导它们向类施万细胞分化。我们还在 PNI 大鼠模型中通过移植进一步检验了这种支架对体内神经再生的功效。我们的结果表明,锂负载的 ENS 在 11 天内逐渐释放锂,释放浓度从 0.02 到(3.64 ± 0.10)mmol/L,并上调了分化的 hADMSCs 中 Wnt/β-catenin 靶基因(cyclinD1 和 c-Myc)以及许旺细胞标志物(生长相关蛋白 43(GAP43)、S100 钙结合蛋白 B(S100B)、胶质纤维酸性蛋白(GFAP)和 SRY-box 转录因子 10(SOX10))的表达。在 PNI 大鼠模型中,植入带/不带细胞的锂负载 ENS 可改善行为特征,如感觉和运动功能,以及损伤神经的电生理特征。对移植了 Li-loaded ENSs 的坐骨神经进行的组织学分析进一步验证了这种功能改善,结果显示没有纤维结缔组织,但有组织的髓鞘轴突增强了。锂负载 ENSs 在促进 hADMSCs 的许旺细胞分化和损伤坐骨神经的轴突再生方面的潜力表明,它们有可能应用于周围神经组织工程。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Enhanced axonal regeneration and functional recovery of the injured sciatic nerve in a rat model by lithium-loaded electrospun nanofibrous scaffolds

Enhanced axonal regeneration and functional recovery of the injured sciatic nerve in a rat model by lithium-loaded electrospun nanofibrous scaffolds

Increasing evidence indicates that engineered nerve grafts have great potential for the regeneration of peripheral nerve injuries (PNIs). While most studies have focused only on the topographical features of the grafts, we have considered both the biophysical and biochemical manipulations in our applied nanoscaffold. To achieve this, we fabricated an electrospun nanofibrous scaffold (ENS) containing polylactide nanofibers loaded with lithium (Li) ions, a Wnt/β‐catenin signaling activator. In addition, we seeded human adipose-derived mesenchymal stem cells (hADMSCs) onto this engineered scaffold to examine if their differentiation toward Schwann-like cells was induced. We further examined the efficacy of the scaffolds for nerve regeneration in vivo via grafting in a PNI rat model. Our results showed that Li-loaded ENSs gradually released Li within 11 d, at concentrations ranging from 0.02 to (3.64 ± 0.10) mmol/L, and upregulated the expression of Wnt/β-catenin target genes (cyclinD1 and c-Myc) as well as those of Schwann cell markers (growth-associated protein 43 (GAP43), S100 calcium binding protein B (S100B), glial fibrillary acidic protein (GFAP), and SRY-box transcription factor 10 (SOX10)) in differentiated hADMSCs. In the PNI rat model, implantation of Li-loaded ENSs with/without cells improved behavioral features such as sensory and motor functions as well as the electrophysiological characteristics of the injured nerve. This improved function was further validated by histological analysis of sciatic nerves grafted with Li-loaded ENSs, which showed no fibrous connective tissue but enhanced organized myelinated axons. The potential of Li-loaded ENSs in promoting Schwann cell differentiation of hADMSCs and axonal regeneration of injured sciatic nerves suggests their potential for application in peripheral nerve tissue engineering.

Graphic abstract

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来源期刊
Bio-Design and Manufacturing
Bio-Design and Manufacturing Materials Science-Materials Science (miscellaneous)
CiteScore
13.30
自引率
7.60%
发文量
148
期刊介绍: Bio-Design and Manufacturing reports new research, new technology and new applications in the field of biomanufacturing, especially 3D bioprinting. Topics of Bio-Design and Manufacturing cover tissue engineering, regenerative medicine, mechanical devices from the perspectives of materials, biology, medicine and mechanical engineering, with a focus on manufacturing science and technology to fulfil the requirement of bio-design.
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