Harley-Troxell Meaghan E, Steiner Richard, Newby Steven D, Bow Austin J, Masi Thomas J, Millis Nicholas, Matavosian Alicia Adina, Crouch Dustin, Stephenson Stacy, Anderson David E, Dhar Madhu
Laboratory of Tissue Engineering and Regenerative Medicine, Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA.
Department of Surgery, University of Tennessee Graduate School of Medicine, Knoxville, TN 37996, USA.
Pharmaceutics. 2024 Sep 27;16(10):1254. doi: 10.3390/pharmaceutics16101254.
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. 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. 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. 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.
周围神经损伤(PNIs)是一个使人衰弱的问题,由于慢性和急性疼痛持续存在,导致生活质量下降。目前修复长度超过10毫米的周围神经损伤的标准做法是使用自体神经移植物。自体神经移植物存在局限性,常常导致运动和感觉障碍无法充分消除的结果。与间充质干细胞(MSCs)结合的仿生纳米复合支架是一种有前景的治疗周围神经损伤的方法。在本研究中,我们研究了聚己内酯(PCL)+氧化石墨烯(GO)的电纺包裹物(有无异种人脂肪组织来源的间充质干细胞(hADMSCs))作为神经组织工程平台的潜力。我们在体外和体内评估了神经包裹物为轴突生长提供支持的潜力。为建立大鼠坐骨神经缺损模型,在18只Lewis大鼠的坐骨神经中制造了一个10毫米长的局限性缺损。将用纳米复合材料治疗的大鼠与接受自体移植治疗的缺损进行比较。在术后12周处死大鼠后进行步态、组织学和肌肉分析。我们的研究结果表明,hADMSCs有向神经谱系转分化的潜力,并且纳米复合材料成功地将hADMSCs递送至损伤部位。组织学上,我们表明含有hADMSCs的PCL + GO纳米复合材料与自体神经移植物相当,能够支持和引导轴突生长。本研究中使用的新型PCL + GO神经包裹物和hADMSCs为构建未来周围神经损伤修复策略奠定了基础。