Composite Biomaterials for Neurite Outgrowth

项目概述：我们的长期目标是双重的：阐明在发育过程中和损伤后轴突引导的细胞和分子机制，并开发支持和增强轴突生长的生物材料平台。我们的工作假设是，多种促进生长的线索的结合将使轴突生长克服局部抑制环境（即神经胶质疤痕），形成损伤后。为了验证这一假设，需要新的平台：(1)以可控和可量化的方式提供促进生长的信号组合；以及(2)提供一种测试刺激环境与抑制环境的方法。这些平台将使创新实验成为可能，这些实验将首次测试引导线索的组合如何在抑制环境中促进轴突生长。NIBIB的使命是通过促进生物工程的基础发现、设计和发展来改善健康，我们的目标是将轴突的生长和方向与刺激和抑制线索的特定数量和比例联系起来，从而为神经再生的新策略奠定基础。这项创新的多学科提案结合了首席研究员在神经元发育、再生和生物材料方面的互补专业知识，以及电化学、微制造和表面表征方面的联合研究员，以制造一个能够提供精确数量的生物引导线索和电刺激的平台（目标1）。目的2侧重于确定特定刺激引导线索（即电刺激和层粘胶蛋白-1）是否在促进神经突生长方面具有协同作用。目的3侧重于确定神经突需要多少刺激来克服抑制环境（即硫酸软骨素蛋白聚糖）。相关性：神经损伤后不能再生，目前的医学实践无法有效地操纵神经再生过程。拟议的研究试图通过量化多种有益的线索如何帮助神经在抑制环境（如神经损伤部位）中生长来解决这个问题。

DESCRIPTION (provided by applicant): Composite Biomaterials for Neurite Outgrowth Project Summary: Our long-term objective is twofold: to elucidate the cellular and molecular mechanisms that underlie axon guidance during development and after injury, and to develop biomaterial platforms to support and enhance axon growth. Our working hypothesis is that the combination of multiple growth- promoting cues will enable axon growth to overcome the local inhibitory environment (i.e., glial scar) that develops post-injury. To test this hypothesis will require new platforms to (1) deliver a combination of growth-promoting cues in a controllable and quantifiable manner; and (2) provide a means by which to test a stimulatory environment against an inhibitory environment. These platforms will make possible innovative experiments that will test for the first time how combinations of guidance cues promote axon growth in an inhibitory environment. Relevant to NIBIB's mission to improve health by promoting fundamental discoveries, design, and development in bioengineering, our objective is to correlate axon growth and direction to specific quantities and ratios of stimulatory and inhibitory cues, thus establishing the basis for new strategies for nerve regeneration. This innovative multidisciplinary proposal combines the complimentary expertise of the Principal Investigator in neuronal development, regeneration, and biomaterials and the Co-Investigator in electrochemistry, microfabrication, and surface characterization, to fabricate a platform capable of delivering precise quantities of both biological guidance cues and electrical stimulation (Aim 1). Aim 2 focuses on determining if specific stimulatory guidance cues (i.e., electrical stimulation, and laminin-1) are synergistic at enhancing neurite growth. Aim 3 focuses on determining how much stimulation is required for neurites to overcome an inhibitory environment (i.e., chondroitin sulfate proteoglycans). Relevance: Nerves fail to regenerate after injury and current medical practice is unable to manipulate effectively the process of nerve regeneration. The proposed research seeks to solve this problem by quantifying how multiple beneficial cues can help nerves to grow in an inhibitory environment such as a nerve injury site.