An engineered graft to encourage preferential motor reinnervation following perip

一种工程移植物，可鼓励围产期后优先运动神经支配

• 批准号: 8551766
• 负责人: Joachim B. Kohn
• 金额: $ 58.05万
• 依托单位: RUTGERS, THE STATE UNIV OF N.J.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-30 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8551766
• 关键词: Address; Anatomy; Animal Model; Area; Autologous; Autologous Transplantation; Biocompatible Materials; Biological; Biomedical Engineering; Biotechnology; Chemicals; Clinical; Collagen; Complement; Computer Simulation; Cues; Development; Devices; Dose; Duct (organ) structure; Dura Mater; Engineering; Enhancers; Esthesia; Face; Family; Fiber; Filler; Growth; Human; Hydrogels; In Vitro; Individual; Infiltration; Injury; Laboratories; Laboratory Study; Length; Libraries; Ligands; Marketing; Measurement; Mechanics; Methods; Modeling; Modification; Morbidity - disease rate; Motor; Motor Neurons; Mus; Muscle; Natural regeneration; Nerve; Nerve Regeneration; Neurobiology; Nutrient; Operative Surgical Procedures; Oryctolagus cuniculus; Patients; Pattern; Peptides; Peripheral; Peripheral Nerves; Peripheral nerve injury; Pharmaceutical Preparations; Polymers; Polysialic Acid; Positioning Attribute; Process; Property; Rattus; Recovery of Function; Research; Research Personnel; Resistance; Rodent Model; Speed; Techniques; Technology; Testing; Therapeutic; Time; Tissues; Translating; Translations; Tube; Tyrosine; Universities; Variant; biodegradable polymer; clinically relevant; controlled release; design; efficacy testing; femoral nerve; flexibility; improved; in vitro testing; in vivo; in vivo Model; injured; innovation; interdisciplinary collaboration; mimetics; motor control; nerve gap; nerve injury; neuromuscular; novel; peptidomimetics; polycarbonate; preclinical study; prevent; prototype; receptor; reinnervation; repaired; scaffold; small molecule; tegaserod; translational medicine

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.

描述（由申请人提供）：生物技术增强周围神经（PN）和随后的功能恢复的重生仍然是一个迫切需要的生物技术。 无法矫正的神经损伤的患者将永久失去运动控制和/或感觉。 尽管PN在本质上具有再生能力，但它们只能在小间隙中统治。 自体神经的嫁接仍然是最好的选择，但是供体的发病率和供应限制仍然有问题。 合成导管进入了市场，但由于较大的差距而无效。 这种生物工程合作伙伴关系旨在通过使用模仿自然增强剂的模拟物与合成导管的现成便利性以及优质的化学和机械性能结合固有再生过程的生物学益处。 罗格斯大学（Rutgers University）的三个实验室已经建立了跨学科的合作，共同解决了用于修复大间隙的外围再生装置的重大障碍。 Melitta Schachner博士已经确定了几种新型化合物，不仅可以提高PNR的速度，而且通过优先针对将再生运动神经元靶向肌肉来提高神经再生的质量。 David Shreiber博士开发了创新的方法，将这些增强剂移植和对用作导管填充剂的临床相关水凝胶进行了模拟，从而增加了活动持续时间并提供空间指导。 最后，约阿希姆·科恩（Joachim Kohn）博士将新颖的聚合物设计与先进的制造方法相结合，以开发可生物降解的聚合物导管，其灵活性对于以受控方式消除生物活性化合物所需的较大间隙所需的灵活性。 研究小组建议（i）开发一个具有可调降解和受控释放配置文件的可降解导管的多功能平台；并优化（ii）在导管内支撑支架上固定增强子的空间呈现，（iii）从导管中释放出的可溶性增强剂的时间表示，（iv）测试设备在大型动物模型中的功效。 通过建立密切的研究合作伙伴关系，应用实验室不仅可以避免创建相互排斥或边缘兼容的组件的陷阱，而且还将实现高级时间范围，以开发这三个组件的最佳组合，以提高PN再生的速度和质量。