An engineered graft to encourage preferential motor reinnervation following perip

描述（由申请人提供）：生物技术增强周围神经（PN）的再生和随后的功能恢复仍然是一个关键的需求。无法矫正的神经损伤患者面临运动控制和/或感觉的永久性丧失。虽然PNs本质上具有再生能力，但它们只能在没有帮助的情况下跨越小间隙。自体神经移植仍然是最好的选择，但供体发病率和供应限制仍然是一个问题。合成管道已进入市场，但由于缺口较大，效果不佳。该生物工程合作伙伴关系旨在通过使用天然生长促进剂的模拟物，将固有再生过程的生物学效益与具有优越化学和机械性能的现成合成导管的便利性结合起来。罗格斯大学（Rutgers University）的三个实验室建立了一个跨学科合作项目，共同解决修复大间隙的外围再生装置的主要障碍。Melitta Schachner博士已经发现了几种新的化合物，它们不仅可以提高PNR的速度，还可以通过优先针对肌肉的再生运动神经元来提高神经再生的质量。David Shreiber博士开发了一种创新的方法，将这些增强剂移植到临床相关的水凝胶上，作为导管填充物，增加了活动的持续时间，并提供了空间引导。最后，Joachim Kohn博士将新型共聚物设计与先进的制造方法相结合，开发出可生物降解的聚合物导管，该导管具有大间隙所需的灵活性，并且能够以可控的方式洗脱生物活性化合物。研究小组建议(i)开发一个可降解导管的多功能平台，该平台具有可调节的降解和可控的释放概况；并优化（ii）在导管内的支撑支架上固定增强剂的空间呈现，（iii）从导管释放的可溶性增强剂的时间呈现，以及（iv）在大间隙动物模型中测试该装置的功效。通过建立密切的研究伙伴关系，应用实验室不仅可以避免创建互斥或边缘兼容组件的陷阱，而且可以实现先进的时间框架来开发这三种组件的最佳组合，以提高PN再生的速度和质量。

DESCRIPTION (provided by applicant): Biotechnology to enhance regeneration of significant lengths of peripheral nerve (PN) and subsequent functional recovery remains a critical need. Patients with uncorrectable nerve injuries face permanent loss of motor control and/or sensation. Although PNs are intrinsically capable of regeneration, they can only do so unaided across small gaps. Grafting of autologous nerve remains the best option, but donor morbidity and supply limitations remain problematic. Synthetic conduits have entered the market but have been ineffective for large gaps. This Bioengineering Partnership aims to combine the biological benefits of the inherent regeneration process through use of mimics of natural growth enhancers with the off-the-shelf convenience of a synthetic conduit with superior chemical and mechanical properties. Three laboratories at Rutgers University have established an interdisciplinary collaboration to jointly address major hurdles for a peripheral regeneration device for repair of large gaps. Dr. Melitta Schachner has identified several novel compounds that enhance not only the speed of PNR, but improve the quality of nerve regeneration by preferentially targeting regenerating motoneurons to muscle. Dr. David Shreiber has developed innovative methods to graft and pattern these enhancers to clinically relevant hydrogels used as conduit fillers, increasing the duration of activity and providing spatial guidance. Lastly, Dr. Joachim Kohn has combined novel co- polymer design with advanced manufacturing approaches to develop biodegradable polymer conduits with the flexibility necessary for large gaps that are additionally capable of eluting the bioactive compounds in a controlled fashion. The research team proposes to (i) develop a versatile platform of degradable conduits with tunable degradation and controlled release profiles; and optimize (ii) the spatial presentation of immobilized enhancers on a supporting scaffold within the conduits, (iii) the temporal presentation of soluble enhancers released from the conduits, and (iv) test the efficacy of the device in a large-gap animal model. By establishing a close research partnership, the applying laboratories will not only avoid the pitfall of creating components that are mutually exclusive or marginally compatible, but will realize an advanced time frame to develop the best possible combination of these three components to enhance the speed and quality of PN regeneration.