The promotion of axon extension in vitro using polymer-templated fibrin scaffolds
The promotion of axon extension in vitro using polymer-templated fibrin scaffolds
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DOI：
10.1016/j.biomaterials.2011.03.037
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发表时间：
2011-07-01
期刊：
影响因子：
14
通讯作者：
Saul, Justin M.
中科院分区：
文献类型：
--
作者：
Scott, John B.;Afshari, Mehdi;Saul, Justin M.
作为修复节段性周围神经缺损的一种手段，生物材料神经袖带是自体和同种异体神经移植的临床替代方法。然而，现有的临床生物材料结构缺乏真正将物理指导线索纳入其设计中。在二维和三维系统中，人们都知道基质的几何形状直接影响轴突的迁移速度。然而，将这些线索整合到具有足够孔隙率的生物材料支架中以促进三维系统中强大的神经再生的能力是一个挑战。我们开发了通过牺牲模板方法制造的纤维蛋白结构，根据模板纤维的直径产生具有多个直径为10-250微米的管道的支架。得到的支架包含大量高度排列的管道，孔隙率接近80%，并显示出与天然神经(150-300kPA杨氏模数)相当的机械性能。我们研究了管道直径对轴突在支架中迁移速度的影响，以研究是否可以利用对这种几何形状的操纵来最终促进支架更快的桥接。所研究的所有直径都会导致轴突迁移，但与其他系统中纤维直径的影响不同，在这些模板支架中，轴突迁移的速度与管道直径无关。然而，与非对齐、曲折的对照相比，对齐的导管确实支持更快的轴突迁移。(C)2011爱思唯尔有限公司。保留所有权利。
Biomaterial nerve cuffs are a clinical alternative to autografts and allografts as a means to repair segmental peripheral nerve defects. However, existing clinical biomaterial constructs lack true incorporation of physical guidance cues into their design. In both two- and three-dimensional systems, it is known that substrate geometry directly affects rates of axon migration. However, the ability to incorporate these cues into biomaterial scaffolds of sufficient porosity to promote robust nerve regeneration in three-dimensional systems is a challenge. We have developed fibrin constructs fabricated by a sacrificial templating approach, yielding scaffolds with multiple 10-250 mu m diameter conduits depending on the diameter of the template fibers. The resulting scaffolds contained numerous, highly aligned conduits, had porosity of similar to 80%, and showed mechanical properties comparable to native nerve (150-300 kPa Young's modulus). We studied the effects of the conduit diameters on the rate of axon migration through the scaffold to investigate if manipulation of this geometry could be used to ultimately promote more rapid bridging of the scaffold. All diameters studied led to axon migration, but in contrast to effects of fiber diameters in other systems, the rate of axon migration was independent of conduit diameter in these templated scaffolds. However, aligned conduits did support more rapid axon migration than non-aligned, tortuous controls. (C) 2011 Elsevier Ltd. All rights reserved.