An injectable, biodegradable hydrogel for trophic factor delivery enhances axonal rewiring and improves performance after spinal cord injury
An injectable, biodegradable hydrogel for trophic factor delivery enhances axonal rewiring and improves performance after spinal cord injury
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DOI：
10.1016/j.expneurol.2006.04.020
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发表时间：
2006-10-01
影响因子：
5.3
通讯作者：
Benowitz, L. I.
中科院分区：
文献类型：
--
作者：
Piantino, J.;Burdick, J. A.;Benowitz, L. I.
脊髓损伤（SCI）后长下降通路的再生失败通常归因于与胶质瘢痕和髓磷脂相关的抑制蛋白，或神经元固有生长能力的丧失，或两者兼而有之。在这里，我们描述了水凝胶作为一种新的方式来传递促进成年大鼠受伤中枢神经系统轴突生长的分子。这种方法利用一种可注射的液体聚合物溶液，当在可见光下被光激活时，它会交联成可生物降解的水凝胶。神经营养因子-3 （NT-3）是一种已知作用于皮质脊髓束（CST）投射神经元的营养因子，被用作促再生分子的原型。在体外建立水凝胶释放特性，以确保在2周内长期持续释放NT-3；这避免了多次注射或微型泵植入的需要。与仅植入水凝胶的对照组相比，水凝胶/ nt -3治疗的动物在露天BBB试验和水平阶梯行走试验中表现出更好的恢复。在解剖水平上，水凝胶/ nt -3处理的动物在运动控制的两个主要下行通路（CST和raphespinal tract）中表现出远高于对照组的轴突生长。在CST的情况下，nt -3诱导的大部分生长表现为未受损的腹侧CST纤维的侧支。这些研究证明了水凝胶技术作为一种临床可行的递送系统在促进脊髓损伤后再生和增强功能预后方面的有效性。(c) 2006爱思唯尔公司版权所有。
The failure of long descending pathways to regenerate after spinal cord injury (SCI) is generally attributed to inhibitory proteins associated with the glial scar and myelin, or to the loss of neurons' intrinsic capacity to grow, or both. Here, we describe the use of hydrogels as a novel way to deliver molecules that promote axon growth in the injured CNS of adult rats. This method utilizes an injectable liquid polymer solution that crosslinks into a biodegradable, water-swollen hydrogel when photoactivated under visible light. Neurotrophin-3 (NT-3), a trophic factor known to act on corticospinal tract (CST) projection neurons, was used as a prototypic pro-regenerative molecule. Hydrogel release properties were established in vitro to ensure long-term, sustained NT-3 release over a 2-week period; this avoided the need for multiple injections or minipump implantation. Hydrogel/NT-3-treated animals showed improved recovery in the open-field BBB test and in a horizontal ladder walk test compared to controls implanted with hydrogel alone. At the anatomical level, hydrogel/NT-3-treated animals showed far greater axon growth than controls in two major descending pathways for motor control, the CST and the raphespinal tract. In the case of the CST, much of the NT-3-induced growth represented collateral branching from undamaged ventral CST fibers. These studies demonstrate the effectiveness of hydrogel technology as a clinically feasible delivery system to promote regeneration and enhance functional outcome after spinal cord injury. (c) 2006 Elsevier Inc. All rights reserved.