Alberti Kyle A, Neufeld Caleb I, Wang Jun, Xu Qiaobing
Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, Massachusetts 02155, United States.
ACS Biomater Sci Eng. 2016 Jun 13;2(6):937-945. doi: 10.1021/acsbiomaterials.6b00034. Epub 2016 May 12.
There is an urgent need for a peripheral nerve repair product that can match or exceed the abilities of the current "gold-standard", nerve autografts. Using a sectioning-based fabrication technique, decellularized tendon sections formed into tubular conduits that maintain the native structure of the collagen. Our previous studies have demonstrated that these collagen structures provide nanotopographical growth guidance cues for regenerating neurons and support glia. Here, the regenerative abilities of the tendon-derived nerve guidance conduits to repair a critically sized defect (15 mm) are evaluated in a rat sciatic nerve model. Using the conduits, functional recovery occurs at a similar rate to isografts, when evaluated with a sciatic function index test. However, muscular recovery, as measured by gastrocnemius weight, was not as great in the conduit-treated group. Both conduit and isograft repairs are histologically evaluated using Masson's trichrome stain and immunofluorescent staining for neurofilament-160 and S100 (markers for neurons and Schwann cells, respectively). This evaluation shows that by week 14, conduits promote regrowth of both neuronal tissue and some physiological support structures, such as blood vessels and epi/perineurium-like structures. Lastly, positive staining for these two markers at week 14 is calculated as a quantitative means of assessment, and shows greater total content of neurofilament-160 and S100 in conduits than in isografts, but a smaller percent area, which may be a result of the greater cross-sectional area of the conduit.
迫切需要一种能与当前“金标准”——神经自体移植相匹配或超越其能力的周围神经修复产品。采用基于切片的制造技术,将脱细胞肌腱切片制成管状导管,该导管保留了胶原蛋白的天然结构。我们之前的研究表明,这些胶原蛋白结构为再生神经元和支持神经胶质细胞提供了纳米拓扑生长引导线索。在此,在大鼠坐骨神经模型中评估了肌腱衍生神经引导导管修复临界尺寸缺损(15毫米)的再生能力。使用该导管,通过坐骨神经功能指数测试评估时,功能恢复的速度与同基因移植相似。然而,通过腓肠肌重量测量的肌肉恢复情况,在导管治疗组中并不那么显著。使用马森三色染色以及针对神经丝蛋白160和S100(分别为神经元和雪旺细胞的标志物)的免疫荧光染色,对导管和同基因移植修复进行组织学评估。该评估表明,到第14周时,导管促进了神经元组织以及一些生理支持结构(如血管和类似外膜/神经束膜的结构)的再生。最后,计算第14周时这两种标志物的阳性染色情况作为定量评估手段,结果显示导管中神经丝蛋白160和S100的总含量高于同基因移植,但所占面积百分比更小,这可能是由于导管横截面积更大所致。