Increasing capillary diameter and the incorporation of gelatin enhance axon outgrowth in alginate-based anisotropic hydrogels
Increasing capillary diameter and the incorporation of gelatin enhance axon outgrowth in alginate-based anisotropic hydrogels
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DOI：
10.1016/j.actbio.2011.04.006
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发表时间：
2011-07-01
影响因子：
9.7
通讯作者：
Weidner, Norbert
中科院分区：
文献类型：
--
作者：
Pawar, Kiran;Mueller, Rainer;Weidner, Norbert
外周和中枢神经系统（CNS）损伤后功能的实质性恢复关键取决于损伤部位的纵向轴突再生，这需要提供支架的机械引导。我们以前已经表明，各向异性的海藻酸盐为基础的水凝胶与一个定义的毛细血管直径（25 μ m），形成通过一个自组织的过程驱动的单向扩散的二价阳离子到海藻酸钠溶胶，促进纵向取向的CNS轴突在体外和体内的伸长。在本研究中，在体外背根神经节生长测定中评估了各种毛细血管直径和明胶掺入促进定向轴突生长和雪旺细胞迁移的影响。将藻酸盐溶胶与含Cu（2+）、Sr（2+）或Zn（2+）离子的溶液叠加，可以分别产生具有直径为18、25和55 μ m的毛细管的水凝胶。轴突生长和雪旺细胞迁移的轴突长度/密度和毛细血管结构内的雪旺细胞密度进行了分析。轴突长入毛细血管水凝胶，这总是伴随着雪旺细胞，增强与毛细血管直径。明胶的掺入不影响整体轴突密度，但促进了水凝胶内轴突生长的长度。在较宽的毛细血管中，轴突的纵向取向降低，这表明中等大小的毛细血管是诱导轴突损伤后大量轴突生长和纵向取向的最佳基底。(C)2011 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
Substantial recovery of function following peripheral and central nervous system (CNS) injury critically depends on longitudinally directed axon regeneration across the injury site, which requires a mechanical guidance providing scaffold. We have previously shown that anisotropic alginate-based hydrogels with a defined capillary diameter (25 mu m), which form via a self-organizing process driven by unidirectional diffusion of divalent cations into sodium alginate sols, promoted longitudinally oriented elongation of CNS axons in vitro and in vivo. In the present study the influence of various capillary diameters and the incorporation of gelatin to promote directed axon outgrowth and Schwann cell migration were assessed in a dorsal root ganglion outgrowth assay in vitro. Superimposing an alginate sol with Cu(2+), Sr(2+), or Zn(2+) ion containing solutions allowed the creation of hydrogels with capillaries 18, 25 and 55 mu m in diameter, respectively. Axon outgrowth and Schwann cell migration were analyzed in terms of axon length/density and Schwann cell density within the capillary structures. Axon ingrowth into capillary hydrogels, which was always accompanied by Schwann cells, was enhanced with increasing capillary diameter. The incorporation of gelatin did not influence overall axon density, but promoted the length of axon outgrowth within the hydrogels. The longitudinal orientation of axons decreased in wider capillaries, which suggests that medium-sized capillaries are the optimal substrate to elicit substantial axon growth and longitudinal orientation after axon injury. (C) 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.