Nanofiber Conduits with a Honeycomb Structure for Repairing Large Defects in Thick Nerves

 描述（由申请人提供）：我们的目标是设计、制造和验证一类新型纳米纤维导管，用于通过恢复其连续性和功能来手术修复横断的周围神经。我们将采取生物工程的方法来修复厚神经中的大缺陷。基于周围神经的解剖学知识，以及涉及其损伤和修复的生物化学和细胞生物学，我们将通过静电纺丝从生物可降解聚合物设计和制造具有蜂窝结构的多管神经引导导管（mNGC）。mNGC将通过将七个小型单管管道的六边形阵列插入到一个大型管道中来构建。小型和大型管道的壁具有三层结构。随机纳米纤维的非织造片材将用作外层以避免手术期间任何可能的撕裂，与单轴对齐纳米纤维的内层一起为轴突延伸提供纵向引导。 一种对温度变化敏感的相变材料（PCM）将被用作一个薄的多孔层，将这两层纳米纤维粘合在一起。PCM将预先装载生物活性分子，用于脉冲释放，以消化抑制性硫酸软骨素蛋白聚糖并促进神经突延伸。每个小导管的内表面也将接种有来自自体骨髓间充质干细胞（BMSC）的许旺细胞，以支持神经突生长。我们将使用能够在人体中重现修复特征的临床相关动物模型对导管进行评估。本研究的范围包括：i）制造 使用电纺纳米纤维的导管; ii）在生物活性分子的脉冲释放下在各种类型的血管支架上的BMSC的分化的体外评价; iii）在大鼠模型中评价单管NGC用于坐骨神经修复的功效;和iv）在绵羊模型中评价多管NGC用于正中神经修复的功效。

 DESCRIPTION (provided by applicant): Our goal is to design, fabricate, and validate a novel class of nanofiber-based conduits for the surgical repair of transected peripheral nerves by restoring their continuity and functions. We will take a bioengineering approach to the repair of large defects in thick nerves. Based on knowledge of the anatomy of a peripheral nerve, as well as the biochemistry and cell biology involved in its injury and repair, we will design and fabricat multi-tubular nerve guidance conduits (mNGCs) with a honeycomb structure from a biodegradable polymer by electrospinning. The mNGC will be constructed by inserting a hexagonal array of seven small, single-tubular conduits into a large conduit. The wall of both small and large conduits has a tri-layer structure. A non-woven sheet of random nanofibers will be used as the outer layer to circumvent any possible tearing during surgery, together with an inner layer of uniaxially aligned nanofibers to provide longitudinal guidance for axonal extension. A phase-change material (PCM) sensitive to temperature change will be applied as a thin, porous layer to glue together these two layers of nanofibers. The PCM will be per-loaded with bioactive molecules for pulse release to digest the inhibitory chondroitin sulfate proteoglycan and promote neurite extension. The inner surface of each small conduit will also be seeded with Schwann cells derived from autologous bone mesenchymal stem cells (BMSCs) to support neurite outgrowth. We will evaluate the conduits using clinically relevant animal models capable of recreating the repair features in humans. The scope of this research includes: i) fabrication of the conduits using electrospun nanofibers; ii) in vitro evaluation of the differentiation of BMSCs on various types of nanofiber scaffolds under pulse release of bioactive molecules; iii) evaluation of the efficacy of single-tubular NGCs for sciatic nerve repair in a rat model; and iv) evaluation of the efficacy of multi-tubular NGCs for median nerve repair in an ovine model.