Immunoengineering Nerve Repair

 描述（由申请人提供）：周围神经损伤是一个严重的临床挑战，在美国每年报告的周围神经损伤病例超过250，000例。在神经创伤后，标准的临床操作程序是将两个神经末端相对并在可能的情况下将它们缝合在一起而不产生张力。虽然自体移植物是当今最好的临床桥接选择，但这种手术存在许多缺点，包括需要二次手术，供体部位功能丧失，可用性有限以及供体或移植部位形成神经瘤。因此，有一个明确的和紧迫的，未满足的临床需要，找到一种替代方法使用自体移植。尽管我们尽了最大的努力，寻找替代的“神经桥”周围神经修复仍然具有挑战性- 在FDA批准用于临床的四种神经“管”中，没有一种通常用于桥接间隙 超过10 mm，因为结果不佳。在这里，我们提出了一个创新的假设-我们假设优先向神经间隙募集抗炎再生单核细胞将使再生级联偏向于帮助桥接长的神经间隙，而不需要长期外源性营养因子递送。具体而言，我们将评估急性递送fractalkine的功效，以研究其吸引再生单核细胞的能力，并随后影响跨越长神经间隙的神经桥接。

 DESCRIPTION (provided by applicant): Peripheral nerve injuries present a serious clinical challenge with greater than 250,000 peripheral nerve trauma cases being reported every year in the United States. After nerve trauma, the standard clinical operating procedure is to oppose the two nerve ends and suture them together without generating tension where possible. While autografts are the best clinical bridging option available today, there are many drawbacks to this procedure, including the need for a secondary surgery, loss of donor site function, limited availability, and neuroma formation at the donor or graft site. Therefore there is a clear and urgent, unmet clinical need to find an alternative approach to the use of autografts. Despite our best efforts, finding alternative 'nerve bridges' for peripheral nerve repair remains challenging - of the four FDA approved nerve 'tubes' for use in the clinic, none is typically used to bridge gaps longer than 10 mm due to poor outcomes. Here, we propose an innovative hypothesis - we hypothesize that recruiting anti- inflammatory regenerative monocytes preferentially to the nerve gap will bias the regenerative cascade to help bridge long nerve gaps without the need for long-term exogenous trophic factor delivery. Specifically we will evaluate the efficacy of acutely delivering fractalkine to investigate its ability to attract regenerative monocytes, and subsequently influence nerve bridging across long nerve gaps.