Biomimetic design of peripheral nerve guides

该奖项由匹兹堡大学材料研究部生物材料项目颁发，旨在将工程创新（由热力学分子间力驱动的界面过程）、蛋白质运输方面的突破以及最近对神经血管交叉对话的见解结合起来，创造出可以诱导神经血管系统共同再生的神经向导。该奖项由化学、生物工程、环境和运输系统部门的界面过程和热力学项目共同创立。周围神经系统再生仍然是一个重大挑战，因为大多数患者的功能恢复有限。目前使用的自体移植物引起供区发病。本项目提出的具有排列微通道的合理设计的生物材料神经导尿管可以避免供体部位的发病率，并可能提供功能恢复。血管转运是维持轴突再生的关键，但这方面目前在神经再生治疗中被忽视。本研究的创新之处在于独特的接触引导和生长因子向细胞的运输。所提出的导向器将具有完全开放的多孔结构，增强传质，同时提供沿导向器通道的定向细胞生长。拟议的指南将使用生长因子的仿生运输来诱导神经血管系统的共同再生。本研究的智力优势在于：1)制备了具有平行微通道的电纺丝神经三维导向器和由聚己内酯和明胶按不同比例制备的微纤维。这个多功能平台将结合使用创新设计的接触指导和生化线索；2)由于许多中枢神经道内具有长而平行的轴突束，因此提出了创新的神经向导设计，以促进中枢神经系统的再生。所描述的研究将为神经导向的新方法提供一个多功能平台。创新的神经引导设计也将影响其他组织的引导再生研究，如心血管再生，其中工程心血管组织的神经控制目前在很大程度上尚未探索。本项目将纳入本研究员对学生的教育活动。研究生和本科生将受益于严格的跨学科培训，在材料科学，生物化学和神经生物学的界面这一前沿研究。此外，研究小组将通过高影响力的期刊向科学界传播这项研究。此外，研究者计划通过新闻发布、社交媒体和互联网向公众通报研究活动。周围神经损伤是一种非常紧张和身体衰弱的损伤，并提出了重大的社会和经济负担。目前的临床方法是从身体的一个部位采集供体神经并将其移植到受伤部位。这带来了许多问题，包括供体部位的神经功能丧失，移植物和受伤神经的大小不匹配。本研究的目的是创造人工神经引导，促进周围神经再生。神经引导系统的设计是基于对健康神经功能和损伤神经在损伤后如何退化的彻底检查。从事这项研究的学生将在一个跨学科的环境中接受培训，探索再生医学的前沿。这将使他们成为下一代神经研究人员的领导者。更广泛地说，该项目的高度转化性质意味着，当成功完成时，周围神经损伤的患者将受益于功能恢复的改善，而不会失去供体部位的神经功能。调查员在拓展活动中非常活跃，例如招募少数民族学生参加研究项目，指导和主持高中研究团队。研究活动将通过互联网和社会媒体通过双周博客传播给尽可能广泛的受众。

This award by the Biomaterials program in the Division of Materials Research to University of Pittsburgh is to combine engineering innovations (interfacial processes driven by thermodynamic intermolecular forces), breakthroughs in protein transport, and recent insights on neurovascular cross talks to create nerve guides that can induce co-regeneration of neurovascular systems. This award is cofounded by the Interfacial Processes and Thermodynamics program in the Division of Chemical, Bioengineering, Environmental, and Transport Systems. Peripheral nerve system regeneration is still a significant challenge because majority of these patients have limited functional recovery. The presently used autografts cause donor site morbidity. Rationally-designed biomaterial nerve guides with aligned microchannels proposed in this project would avoid donor site morbidity and may offer functional recovery. Vascular transport is critical to sustain regenerating axons, and yet this aspect is at present overlooked in nerve regeneration treatments. The innovation of this research is in the unique presentation of contact guidance and transport of growth factors to the cells. The proposed guide will have a completely open porous structure that enhances mass transfer while providing directed cell growth along the guidance channels. The proposed guide will use biomimetic transport of growth factors to induce co-regeneration of the neurovascular systems. The intellectual merit of this research is in: 1) the preparation of electrospun nerve 3D guides with parallel microchannels and microfibers prepared from polycaprolactone and gelatin at different ratios. This versatile platform will incorporate contact guidance and biochemical cues using innovative designs; and 2) the proposed innovative design of the nerve guide that will enhance the regeneration of central nerve system because many central nerve tracks have long parallel axon bundles within the track. The described research would generate a versatile platform for a new approach to nerve guides. The innovative nerve guide design will also impact research for the guided regeneration of other tissues such as cardiovascular regeneration, where nerve control of engineered cardiovascular tissues is largely unexplored at present. This project will be integrated into this researcher's educational activities of students. The graduate and undergraduate students will benefit from rigorous interdisciplinary training in this cutting edge research at the interface of materials science, biochemistry, and neurobiology. Furthermore, the research team will disseminate this research to the scientific community through high impact journals. Additionally, the investigator plans to inform the general public about the research activities by news releases, social media and internet.Peripheral nerve injury is a very stressful and physically debilitating injury, and presents a significant societal and economic burden. The current clinical approach is by harvesting a donor nerve from one site of the body and transplanting it to the injury site. This presents a multitude of problems including losing nerve functions at the donor site, and size mismatch of the graft and the injured nerve. The goal of this research is to create man-made nerve guides that promote peripheral regeneration of nerve. The nerve-guide design is based on thorough examinations of how healthy nerve functions and how injured nerve degenerate after injury. Students working on this research will be trained in a cross-disciplinary environment exploring the frontiers of regenerative medicine. This will prepare them to become leaders of the next generation researchers in neural studies. More broadly, the highly translational nature of this project means that when successfully completed, patients suffering from peripheral nerve injuries will benefit from improved functional recovery without loss of nerve function at the donor site. The investigator is very active in outreach activities such as recruiting minority students into research programs, and mentoring and hosting high school research teams. The research activities will be disseminated to broadest possible audience through biweekly blogs through internet and social media.