Biomimetic design of peripheral nerve guides

该奖项由匹兹堡大学材料研究部的生物材料项目颁发，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相结合，创造出能够诱导神经血管系统共同再生的神经指南。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设立。周围神经系统的再生仍然是一个巨大的挑战，因为这些患者中的大多数人功能恢复有限。目前使用的自体移植物造成供区并发症。本项目中提出的具有排列微通道的合理设计的生物材料神经导向器将避免供体部位的并发症，并可能提供功能恢复。血管运输是维持再生轴突的关键，然而目前神经再生治疗忽略了这一方面。本研究的创新之处在于独特地提出了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，其在沿导向通道提供定向细胞生长的同时增强传质。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。本研究的智力价值在于：1)以不同比例的聚己内酯和明胶制备具有平行微通道和微纤维的电纺神经3D导向器。这一多功能平台将利用创新的设计结合接触指导和生化提示；以及2)拟议的神经引导创新设计，将增强中枢神经系统的再生，因为许多中枢神经轨迹在轨迹内有长的平行轴突束。所描述的研究将为神经指南的新方法提供一个通用的平台。这种创新的神经引导设计也将影响其他组织的引导再生研究，例如心血管再生，目前在工程心血管组织的神经控制方面还很少有人探索。该项目将融入到这位研究人员的学生教育活动中。研究生和本科生将受益于材料科学、生物化学和神经生物学这一前沿研究领域的严格跨学科培训。此外，研究小组将通过影响较大的期刊向科学界传播这项研究。此外，研究人员计划通过新闻稿、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有压力和身体虚弱的损伤，并带来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获取供体神经，并将其移植到损伤部位。这带来了一系列的问题，包括供体部位的神经功能丧失，以及移植物和受损神经的大小不匹配。这项研究的目标是创造人造神经导向器，促进神经的外周再生。神经导引设计是基于对健康神经如何功能以及受伤神经在受伤后如何退化的彻底检查。从事这项研究的学生将在探索再生医学前沿的跨学科环境中接受培训。这将使他们做好准备，成为神经研究领域下一代研究人员的领导者。更广泛地说，这个项目的高度翻译性意味着，当成功完成时，周围神经损伤患者将受益于改善功能恢复，而不会失去供体部位的神经功能。这位调查员非常积极地参与外展活动，例如招募少数族裔学生参加研究项目，以及指导和主持高中研究团队。研究活动将通过互联网和社交媒体的双周博客向尽可能广泛的受众传播。

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.