Rational and Combinatorial Design of Biomaterials for Neural Engineering

一些因素，如瘢痕组织的形成、抑制性髓鞘的不充分去除、细胞死亡和缺乏允许的底物或生长因子，限制了神经元在损伤后再生的能力。指导原理是，为周围神经系统的驻留神经细胞（感觉神经元和运动神经元）和驻留非神经细胞（许旺细胞和内皮细胞）设计的组织特异性生物材料与适当的可溶性因子相结合，可以作为上级神经引导通道的基础，以解决这些挑战。合理的和组合的设计策略，协同细胞外基质蛋白质和可溶性因子的组合产生再生轴突和支持细胞的组织特异性生物材料的发现将被应用在生理相关的三维环境。目的是系统地筛选基质蛋白，基础支架和可溶性因子组合的大子集，以合理地设计用于周围神经系统的复合生物材料。长期目标是设计一种生物材料用于治疗大间隙周围神经损伤。新的高通量筛选平台，如本研究中提出的那些，将加速发现周围神经大间隙损伤的治疗相关生物材料。这个灵活的平台可以进一步扩展，以筛选脊髓损伤、创伤性脑损伤和神经退行性疾病细胞治疗的最佳材料。如果成功，拟议的研究将（1）开发一个新的框架，以检查一个非常大的实验空间，用于蛋白质，支架和可溶性因子的可能组合，由于时间的原因，努力和成本（2）鉴定细胞特异性的新型生物材料，其将用作引导通道的基础以促进神经元生长和/或与外周神经损伤相关的非神经元细胞的迁移/再增殖，（3）将与大间隙外周神经损伤相关的生物材料转化为脑或脊髓损伤，以及（4）将这种高-通量筛选平台合理地生成用于其他感兴趣的靶组织的生物材料候选物。更广泛的影响：如果成功，（1）拟议的研究将开发一种支持神经修复的生物材料。(2)这项研究将包括高中生和本科生研究人员的参与。(3)研究结果将在国家/区域会议上广泛传播，手稿将在同行评审的期刊上发表，并将应邀发表演讲。 (4)由该项目资助的主要研究人员和研究生将通过提供广泛基于神经工程的短期研讨会来鼓励K-12对科学，技术，工程和医学（STEM领域）的兴趣。

1067208ThompsonSeveral factors such as formation of scar tissue, inadequate removal of inhibitory myelin, cell death and lack of a permissive substrate or growth factors limit the ability of neurons to regenerate after an injury. The guiding rationale is that a tissue-specific biomaterial designed for both resident neural (sensory and motor neurons) and resident non-neural cells (Schwann cells and endothelial cells) of the peripheral nervous system combined with the appropriate soluble factors can serve as the foundation for a superior nerve guidance channel to address these challenges. Rational and combinatorial design strategies for the discovery of synergistic extracellular matrix proteins and soluble factors combinations generating a tissue-specific biomaterial for regenerating axons and support cells will be applied in a physiologically-relevant 3-dimensional environment. The objective is to systematically screen a large subset of matrix proteins, base scaffolds and soluble factors combinations to rationally design composite biomaterials for the peripheral nervous system. The long-term goal is to engineer a biomaterial for treatment of large-gap peripheral nerve injuries. Novel high throughput screening platforms, such as those proposed in this study, will accelerate the discovery of therapeutically relevant biomaterials for large-gap injuries of the peripheral nerve. This flexible platform can be further extended to screen for materials optimal for spinal cord injury, traumatic brain injury, and cell-based therapies for neurodegenerative diseases.Intellectual Merit: If successful, the proposed research will (1) develop a new framework to examine a prohibitively large experimental space for possible combinations of proteins, scaffolds and soluble factors that by conventional methods due to the time, effort and cost (2) identify cell-specific, novel biomaterial that will serve as a basis of a guidance channel to both promote neuronal growth and/or the migration/re-population of non-neuronal cells relevant to peripheral nerve injury, (3) translation of biomaterials relevant to large-gap peripheral nerve injury to injuries in the brain or spinal cord and (4) apply this high-throughput screening platform rationally generate biomaterial candidates for other target tissues of interest. Broader Impact: If successful, (1) the proposed research will develop a biomaterial to support nerve repair. (2) The research will include the participation of both high school students and undergraduate researchers. (3) Research findings will be broadly disseminated at national/regional meetings, manuscripts in peer-reviewed journals, and invited lectures. (4) Both Principal Investigators and graduate students funded by this project will volunteer by presenting short workshops broadly based on neural engineering to encourage K-12 interest in the Science, Technology, Engineering and Medicine (STEM fields).