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Bio-Design and Manufacturing  2024 Vol.7 No.5 P.701-720

http://doi.org/10.1007/s42242-024-00304-3


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


Author(s):  Banafsheh Dolatyar, Bahman Zeynali, Iman Shabani, Azita Parvaneh Tafreshi, Reza Karimi-Soflou

Affiliation(s):  Developmental Biology Lab., School of Biology, College of Science, University of Tehran, Tehran, Iran; more

Corresponding email(s):   zeynalib@ut.ac.ir, shabani@aut.ac.ir

Key Words:  Stem cell, Schwann cell differentiation, Electrospun nanofibrous scaffold, Lithium ion, Nerve regeneration


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Banafsheh Dolatyar, Bahman Zeynali, Iman Shabani, Azita Parvaneh Tafreshi, Reza Karimi-Soflou. Enhanced axonal regeneration and functional recovery of the injured sciatic nerve in a rat model by lithium-loaded electrospun nanofibrous scaffolds[J]. Journal of Zhejiang University Science D, 2024, 7(5): 701-720.

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Abstract: 
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.

伊朗德黑兰大学Bahman Zeynali等 | 锂负载电纺丝纳米纤维支架增强大鼠坐骨神经轴突再生和功能恢复

本研究论文聚焦锂负载电纺丝纳米纤维支架增强大鼠坐骨神经轴突再生和功能恢复。越来越多的证据表明,经过工程改造的神经移植在周围神经损伤(PNIs)再生方面具有巨大潜力。虽然大多数研究仅关注移植物的形貌特征,但我们在应用纳米支架时考虑了生物物理学和生物化学两个方面。为了实现这一点,我们制造了一种含有聚乳酸纳米纤维和锂离子(Li)的静电纺纳米支架(ENS),其中的锂离子是一种Wnt/β-连环蛋白信号激活剂。此外,我们将人类脂肪来源的间充质干细胞(hADMSCs)种植到这种工程支架上,以检查是否能诱导它们向施旺样细胞分化。我们还通过在PNI大鼠模型中进行移植来进一步检查支架在神经再生方面的功效。结果显示,含锂的ENS在11天内逐渐释放锂,其浓度在0.02至(3.64±0.10) mmol/L范围内,并上调了已分化的hADMSCs中的Wnt/β-连环蛋白靶基因(cyclinD1和c-Myc)以及施旺细胞标记物(重组生长相关蛋白43(GAP43)、单克隆抗体S100钙结合蛋白B(S100B)、胶质酸性纤维蛋白(GFAP)和SOX10)的表达。在PNI大鼠模型中,植入含锂的ENS(是否有细胞)改善了感觉和运动功能以及受伤神经的电生理特性等行为特征。通过对植入锂离子支架的坐骨神经进行组织学分析,进一步验证了这种改善的功能,结果显示没有纤维结缔组织,而是增强了有机化的髓鞘轴突。锂离子饱和的ENS在促进hADMSCs的施旺细胞分化和受伤坐骨神经轴突再生方面的潜力,表明其在周围神经组织工程中的应用潜力。

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