Relationship between scaffold channel diameter and number of regenerating axons in the transected rat spinal cord.

Relationship between scaffold channel diameter and number of regenerating axons in the transected rat spinal cord.
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DOI:
10.1016/j.actbio.2009.03.021
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发表时间:
2009-09
期刊:
影响因子:
9.7
通讯作者:
Windebank, Anthony J.
Windebank, Anthony J.
中科院分区:
工程技术1区
文献类型:
--
作者:
Krych, Aaron J.;Rooney, Gemma E.;Chen, Bingkun;Schermerhorn, Thomas C.;Ameenuddin, Syed;Gross, LouAnn;Moore, Michael J.;Currier, Bradford L.;Spinner, Robert J.;Friedman, Jonathan A.;Yaszemski, Michael J.;Windebank, Anthony J.

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通过雪旺细胞(SC)种子支架植入的内源性轴突再生已经在横断的大鼠脊髓中得到证实。支架通道中细胞衬里的形成可能限制轴突再生的程度。横切成年大鼠脊髓,植入含有7个直径为450-μm (n=19)或660-μm (n=14)的sc负载的聚乳酸共乙醇酸(PLGA)支架植入物。动物分别在1、2和3个月后被处死。免疫组化检测神经丝表达。计算了纤维组织和再生芯的截面积。我们发现,450 μm支架在1个月(186±37)和3个月(78±11)时,每个通道的轴突纤维数量显著高于660 μm支架(分别为90±19和40±6)(P=0.0164和0.0149)。450 μm和660 μm通道的纤维边缘面积差异在1个月时最为明显,分别为28,046 μm2±6,551和58,633 μm2±7,063 (P=0.0105)。我们的研究表明,与直径较大的支架相比,直径较小的支架可以促进更大的再生。在较大的通道中,由于产生了较大的纤维边缘,轴突再生减少。该支架环境的优化为进一步研究细胞类型、营养因子或药物对损伤脊髓再生能力的影响奠定了基础。
Regeneration of endogenous axons through a Schwann cell (SC)-seeded scaffold implant has been demonstrated in the transected rat spinal cord. The formation of a cellular lining in the scaffold channel may limit the degree of axonal regeneration. Spinal cords of adult rats were transected and implanted with the SC-loaded polylactic co-glycollic acid (PLGA) scaffold implants containing seven parallel-aligned channels, either 450-μm (n=19) or 660-μm in diameter (n=14). Animals were sacrificed after 1, 2, and 3 months. Immunohistochemistry for neurofilament-expression was performed. The cross-sectional area of fibrous tissue and regenerative core was calculated. We found that the 450-μm scaffolds had significantly greater axon fibers per channel at the one month (186 ± 37) and three month (78 ± 11) endpoints than the 660-μm scaffolds (90 ± 19 and 40 ± 6, respectively) (P=0.0164 & 0.0149, respectively). The difference in the area of fibrous rim between the 450-μm and 660-μm channels was most pronounced at the one month endpoint, at 28,046 μm2 ± 6,551 and 58,633 μm2 ± 7,063, respectively (P=0.0105). Our study suggests that fabricating scaffolds with smaller diameter channels promotes greater regeneration over larger diameter channels. Axonal regeneration was reduced in the larger channels due to the generation of a large fibrous rim. Optimization of this scaffold environment establishes a platform for future studies of the effects of cell types, trophic factors or pharmacological agents on the regenerative capacity of the injured spinal cord.
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