Alignment and composition of laminin-polycaprolactone nanofiber blends enhance peripheral nerve regeneration.
Alignment and composition of laminin-polycaprolactone nanofiber blends enhance peripheral nerve regeneration.
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DOI：
10.1002/jbm.a.33204
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发表时间：
2012-02
影响因子：
4.9
通讯作者：
Botchwey, Edward A.
中科院分区：
文献类型：
--
作者：
Neal, Rebekah A.;Tholpady, Sunil S.;Foley, Patricia L.;Swami, Nathan;Ogle, Roy C.;Botchwey, Edward A.
周围神经横断通常发生在创伤性损伤中，导致损伤部位远端的缺损。目前市场上用于维修的导管是中空管;然而，它们经常由于长间隙的缓慢再生而失效。为了促进再生速度和功能恢复，理想的管道应该提供生化相关信号和物理指导线索，从而在再生中发挥积极作用。为此，制备了层粘连蛋白和层粘连蛋白-聚己内酯（PCL）共混纳米纤维来模拟周围神经基底膜。在体外测定中确定的10%（wt）层粘连蛋白含量足以保留层粘连蛋白的神经突促进作用。此外，改进的集电板设计引入绝缘间隙，使对齐的纳米纤维的制造。在大鼠胫神经缺损模型中，评价层粘连蛋白含量和纤维取向的影响。导管的内腔填充有不同层粘连蛋白含量和排列的网状物，以评估运动和感觉恢复的变化。在6周时，接受对齐的双导管的动物的逆行神经传导速度明显快于接受随机双导管的动物。接受纳米纤维填充导管的动物在顺行和逆行方向上均显示出一定的传导，而在接受中空导管的动物中，未检测到脉冲传导。排列的PCL纳米纤维显著改善了运动功能;排列的层粘连蛋白共混物纳米纤维产生了最好的感觉功能恢复。在这两种情况下，纳米纤维填充导管导致比中空导管更好的功能恢复。这些研究为使用天然-合成共混电纺纳米纤维来增强现有的中空神经引导导管提供了坚实的基础。
Peripheral nerve transection occurs commonly in traumatic injury, causing deficits distal to the injury site. Conduits for repair currently on the market are hollow tubes; however, they often fail due to slow regeneration over long gaps. To facilitate increased regeneration speed and functional recovery, the ideal conduit should provide biochemically relevant signals and physical guidance cues, thus playing an active role in regeneration. To that end, laminin and laminin–polycaprolactone (PCL) blend nanofibers were fabricated to mimic peripheral nerve basement membrane. In vitro assays established 10% (wt) laminin content is sufficient to retain neurite-promoting effects of laminin. In addition, modified collector plate design to introduce an insulating gap enabled the fabrication of aligned nanofibers. The effects of laminin content and fiber orientation were evaluated in rat tibial nerve defect model. The lumens of conduits were filled with nanofiber meshes of varying laminin content and alignment to assess changes in motor and sensory recovery. Retrograde nerve conduction speed at 6 weeks was significantly faster in animals receiving aligned nanofiber conduits than in those receiving random nanofiber conduits. Animals receiving nanofiber-filled conduits showed some conduction in both anterograde and retrograde directions, whereas in animals receiving hollow conduits, no impulse conduction was detected. Aligned PCL nanofibers significantly improved motor function; aligned laminin blend nanofibers yielded the best sensory function recovery. In both cases, nanofiber-filled conduits resulted in better functional recovery than hollow conduits. These studies provide a firm foundation for the use of natural–synthetic blend electrospun nanofibers to enhance existing hollow nerve guidance conduits.
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