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)：生物技术促进较长长度的周围神经(PN)的再生和随后的功能恢复仍然是一个迫切的需要。无法纠正的神经损伤患者将面临永久性的运动控制和/或感觉丧失。尽管PN天生就有再生的能力，但它们只能在没有人帮助的情况下跨越很小的缺口。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存在问题。合成管道已经进入市场，但对于很大的缺口来说，效果不佳。这一生物工程伙伴关系旨在通过使用仿制的天然生长促进剂，将固有再生过程的生物益处与具有优异化学和机械性能的合成管道的现成便利性相结合。罗格斯大学的三个实验室建立了跨学科合作，共同解决修复大缺口的外围再生设备的主要障碍。Melitta Schachner博士已经确定了几种新的化合物，这些化合物不仅可以提高PNR的速度，而且通过优先靶向肌肉再生的运动神经元来改善神经再生的质量。David Shreiber博士开发了创新的方法，将这些增强剂嫁接到临床相关的水凝胶上，用作管道填充物，延长了活动时间，并提供了空间指导。最后，Joachim Kohn博士将新颖的共聚设计与先进的制造方法相结合，开发了可生物降解的聚合物导管，具有大间隙所需的灵活性，此外还能够以受控方式洗脱生物活性化合物。研究小组建议(I)开发一种多功能的可降解导管平台，具有可调节的降解和可控释放轮廓；并优化(Ii)固定化增强剂在导管内的支撑支架上的空间呈现，(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效果。通过建立密切的研究伙伴关系，应用实验室不仅将避免创建相互排斥或略微兼容的组件的陷阱，而且将实现提前的时间框架，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。