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

 描述(申请人提供)：我们的目标是设计、制造和验证一种新型的基于纳米纤维的导管，通过恢复其连续性和功能来用于手术修复切断的周围神经。我们将采用生物工程的方法修复粗大神经的大缺陷。基于周围神经的解剖学知识，以及与周围神经损伤和修复相关的生物化学和细胞生物学，我们将通过静电纺丝的方法设计和制造具有蜂窝结构的多管神经引导导管(MNGCs)。MNGC将通过将由七个小的单管管道组成的六角形阵列插入到一个大管道中来构建。小型和大型管道的壁面均为三层结构。一层无纺布的随机纳米纤维将被用作外层，以避免手术中任何可能的撕裂，以及一层单轴排列的纳米纤维内层，为轴突延伸提供纵向指导。 一种对温度变化敏感的相变材料(PCM)将被用作一层薄的多孔层，将这两层纳米纤维粘合在一起。PCM将预载生物活性分子用于脉冲释放，以消化抑制的硫酸软骨素蛋白多糖，并促进轴突延伸。每个小管道的内表面也将种植来自自体骨髓间充质干细胞(BMSCs)的雪旺细胞，以支持轴突生长。我们将使用临床相关的动物模型来评估这些管道，这些动物模型能够在人类身上重现修复功能。这项研究的范围包括：i)制造 研究内容包括：i)研究了电纺纳米纤维在不同类型的纳米纤维支架上诱导BMSCs分化的作用；ii)脉冲释放活性分子对BMSCs在不同类型纳米纤维支架上分化的影响；iii)对单管NGCs修复大鼠坐骨神经损伤的有效性进行评估；以及iv)对多管NGCs修复正中神经损伤的绵羊模型进行评估。

 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.