Electrospun PCL Nerve Wrap Coated with Graphene Oxide Supports Axonal Growth in a Rat Sciatic Nerve Injury Model.

IF 4.9 3区 医学 Q1 PHARMACOLOGY & PHARMACY
Meaghan E Harley-Troxell, Richard Steiner, Steven D Newby, Austin J Bow, Thomas J Masi, Nicholas Millis, Alicia Adina Matavosian, Dustin Crouch, Stacy Stephenson, David E Anderson, Madhu Dhar
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Abstract

Background/Objectives: Peripheral nerve injuries (PNIs) are a debilitating problem, resulting in diminished quality of life due to the continued presence of both chronic and acute pain. The current standard of practice for the repair of PNIs larger than 10 mm is the use of autologous nerve grafts. Autologous nerve grafts have limitations that often result in outcomes that are not sufficient to remove motor and sensory impairments. Bio-mimetic nanocomposite scaffolds combined with mesenchymal stem cells (MSCs) represent a promising approach for PNIs. In this study, we investigated the potential of an electrospun wrap of polycaprolactone (PCL) + graphene oxide (GO), with and without xenogeneic human adipose tissue-derived MSCs (hADMSCs) to use as a platform for neural tissue engineering. Methods: We evaluated, in vitro and in vivo, the potential of the nerve wrap in providing support for axonal growth. To establish the rat sciatic nerve defect model, a 10 mm long limiting defect was created in the rat sciatic nerve of 18 Lewis rats. Rats treated with the nanocomposites were compared with autograft-treated defects. Gait, histological, and muscle analyses were performed after sacrifice at 12 weeks post-surgery. Results: Our findings demonstrate that hADMSCs had the potential to transdifferentiate into neural lineage and that the nanocomposite successfully delivered hADMSCs to the injury site. Histologically, we show that the PCL + GO nanocomposite with hADMSCs is comparable to the autologous nerve graft, to support and guide axonal growth. Conclusions: The novel PCL + GO nerve wrap and hADMSCs used in this study provide a foundation on which to build upon and generate future strategies for PNI repair.

涂有氧化石墨烯的电纺 PCL 神经包膜可支持大鼠坐骨神经损伤模型中的轴突生长
背景/目标:周围神经损伤(PNIs)是一个使人衰弱的问题,由于持续存在慢性和急性疼痛,导致生活质量下降。目前,修复 10 毫米以上周围神经损伤的标准做法是使用自体神经移植物。自体神经移植有其局限性,其结果往往不足以消除运动和感觉障碍。生物仿生纳米复合支架与间充质干细胞(MSCs)的结合是一种很有前景的PNI方法。在本研究中,我们研究了聚己内酯(PCL)+氧化石墨烯(GO)的电纺丝包覆材料与异种人脂肪组织间充质干细胞(hADMSCs)和不与异种人脂肪组织间充质干细胞(hADMSCs)结合作为神经组织工程平台的潜力。方法:我们在体外和体内评估了神经包膜为轴突生长提供支持的潜力。为了建立大鼠坐骨神经缺损模型,我们在 18 只 Lewis 大鼠的坐骨神经上创建了一个 10 毫米长的局限性缺损。使用纳米复合材料治疗的大鼠与自体移植治疗的缺损大鼠进行了比较。在手术后 12 周处死大鼠后进行步态、组织学和肌肉分析。结果:我们的研究结果表明,hADMSCs 具有向神经系转分化的潜力,而且纳米复合材料成功地将 hADMSCs 运送到了损伤部位。从组织学角度看,我们发现含有 hADMSCs 的 PCL + GO 纳米复合材料在支持和引导轴突生长方面与自体神经移植效果相当。结论本研究中使用的新型 PCL + GO 神经包膜和 hADMSCs 为未来的 PNI 修复策略奠定了基础。
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来源期刊
Pharmaceutics
Pharmaceutics Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
7.90
自引率
11.10%
发文量
2379
审稿时长
16.41 days
期刊介绍: Pharmaceutics (ISSN 1999-4923) is an open access journal which provides an advanced forum for the science and technology of pharmaceutics and biopharmaceutics. It publishes reviews, regular research papers, communications,  and short notes. Covered topics include pharmacokinetics, toxicokinetics, pharmacodynamics, pharmacogenetics and pharmacogenomics, and pharmaceutical formulation. Our aim is to encourage scientists to publish their experimental and theoretical details in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.
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