Multiple-channel scaffolds to promote spinal cord axon regeneration

Multiple-channel scaffolds to promote spinal cord axon regeneration
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DOI:
10.1016/j.biomaterials.2005.07.045
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发表时间:
2006-01-01
期刊:
影响因子:
14
通讯作者:
Yaszemski, MJ
Yaszemski, MJ
中科院分区:
工程技术1区
文献类型:
--
作者:
Moore, MJ;Friedman, JA;Yaszemski, MJ

文献摘要

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随着脊髓损伤的分子、细胞和组织水平治疗方法的发现,这些治疗方法的组合很可能是引起动物模型或患者功能恢复所必需的。我们描述了多通道,可生物降解的支架,作为一个模型的基础上,同时调查的支架结构,移植的细胞,和局部传递的分子剂对轴突再生的影响。这些初始实验使用共聚物比例为85:15的聚(乳酸-共-乙醇酸)(PLGA)。具有快速溶剂蒸发的注射成型产生具有多个不同通道的支架,所述通道沿支架的长度平行沿着延伸。证明了创建具有各种通道尺寸和几何形状的支架的可行性。发现分离开放通道的壁具有高达89%的空隙率,通过220 μ m或更大的连接可达到高达90%的空隙率。支架在体外降解了30周,在此期间观察到了12周的替代药物的持续递送。原代新生雪旺细胞分布在支架的通道中,并在组织培养中保持活力至少48小时。将含有施万细胞的支架植入横断的成年大鼠脊髓中,在术后一个月含有再生轴突。轴突再生证明了三维重建的系列组织切片。(c)2005爱思唯尔有限公司保留所有权利。
As molecular, cellular, and tissue-level treatments for spinal cord injury are discovered, it is likely that combinations of such treatments will be necessary to elicit functional recovery in animal models or patients. We describe multiple-channel, biodegradable scaffolds that serve as the basis for a model to investigate simultaneously the effects on axon regeneration of scaffold architecture, transplanted cells, and locally delivered molecular agents. Poly(lactic-co-glycolic acid) (PLGA) with copolymer ratio 85:15 was used for these initial experiments. Injection molding with rapid solvent evaporation resulted in scaffolds with a plurality of distinct channels running parallel along the length of the scaffolds. The feasibility of creating scaffolds with various channel sizes and geometries was demonstrated. Walls separating open channels were found to possess void fractions as high as 89%, with accessible void fractions as high as 90% through connections 220 pm or larger. Scaffolds degraded in vitro over a period of 30 weeks, over which time-sustained delivery of a surrogate drug was observed for 12 weeks. Primary neonatal Schwann cells were distributed in the channels of the scaffold and remained viable in tissue culture for at least 48 h. Schwann-cell containing scaffolds implanted into transected adult rat spinal cords contained regenerating axons at one month post-operation. Axon regeneration was demonstrated by three-dimensional reconstruction of serial histological sections. (c) 2005 Elsevier Ltd. All rights reserved.