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: 8703551
• 负责人: Joachim B. Kohn
• 金额: $ 57.7万
• 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/8703551
• 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）：增强周围神经（PN）显著长度的再生和随后的功能恢复的生物技术仍然是一个关键需求。 无法矫正的神经损伤患者面临永久性运动控制和/或感觉丧失。 虽然PN本质上具有再生能力，但它们只能在没有辅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。 合成导管已经进入市场，但对大的缺口无效。 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益处与具有上级化学和机械性能的合成导管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，共同解决外周再生装置修复大间隙的主要障碍。 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，而且可以通过优先将再生的运动神经元靶向肌肉来提高神经再生的质量。 大卫Shreiber博士已经开发出创新的方法，将这些增强剂移植和图案化到临床相关的水凝胶中，用作导管填充物，增加活动的持续时间并提供空间指导。 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，开发出具有大间隙所需灵活性的可生物降解聚合物导管，这些导管还能够以受控的方式洗脱生物活性化合物。 该研究小组建议（i）开发一种具有可调降解和控释特性的可降解导管的通用平台;并优化（ii）导管内支撑支架上固定化增强剂的空间呈现，（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相互排斥或勉强兼容的组件的陷阱，而且可以实现提前的时间框架，以开发这三种组件的最佳组合，以提高PN再生的速度和质量。