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
Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Acta Biomater. 2009 Sep;5(7):2551-9. doi: 10.1016/j.actbio.2009.03.021. Epub 2009 Mar 27.
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 450mum (n=19) or 660microm in diameter (n=14). Animals were sacrificed after 1, 2 and 3months. Immunohistochemistry for neurofilament expression was performed. The cross-sectional area of fibrous tissue and regenerative core was calculated. We found that the 450microm scaffolds had significantly greater axon fibers per channel at the 1month (186+/-37) and 3month (78+/-11) endpoints than the 660microm scaffolds (90+/-19 and 40+/-6, respectively) (p=0.0164 and 0.0149, respectively). The difference in the area of fibrous rim between the 450 and 660microm channels was most pronounced at the 1month endpoint, at 28,046+/-6551 and 58,633+/-7063microm(2), 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.
在横断的大鼠脊髓中，已证实通过接种雪旺细胞（SC）的支架植入可实现内源性轴突的再生。支架通道中细胞内衬的形成可能会限制轴突再生的程度。将成年大鼠的脊髓横断，并植入含有七个平行排列通道的负载SC的聚乳酸-乙醇酸共聚物（PLGA）支架植入物，通道直径分别为450μm（n = 19）或660μm（n = 14）。在1、2和3个月后处死动物。进行神经丝表达的免疫组织化学检测。计算纤维组织和再生核心的横截面积。我们发现，在1个月（186±37）和3个月（78±11）的观察终点，450μm的支架每个通道的轴突纤维明显多于660μm的支架（分别为90±19和40±6）（p分别为0.0164和0.0149）。450μm和660μm通道之间纤维边缘面积的差异在1个月观察终点最为明显，分别为28,046±6551和58,633±7063μm²（p = 0.0105）。我们的研究表明，制造直径较小通道的支架比直径较大的通道能促进更大程度的再生。由于形成了较大的纤维边缘，较大通道中的轴突再生减少。这种支架环境的优化为未来研究细胞类型、营养因子或药物制剂对损伤脊髓再生能力的影响建立了一个平台。
