Composite Biomaterials for Neurite Outgrowth

用于神经突生长的复合生物材料

• 批准号: 7230222
• 负责人: Diane Hoffman-Kim
• 金额: $ 19.24万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7230222
• 关键词: Adhesions; Affect; Andro-Diane; Attention; Axon; Biocompatible Materials; Biological; Biomedical Engineering; Charge; Chemicals; Chondroitin Sulfate Proteoglycan; Cicatrix; Classification; Complex; Cues; Development; Dimensions; Electric Conductivity; Electric Stimulation; Electrochemistry; Electroplating; Engineering; Environment; Equilibrium; Exhibits; Extracellular Matrix; Family; Film; Glutamic Acid; Goals; Growth; Health; Human; Individual; Injury; Knowledge; Measurement; Measures; Mediating; Medical; Methods; Microfabrication; Mission; Molecular; Monitor; Natural regeneration; Nerve; Nerve Regeneration; Nerve Tissue; Nervous system structure; Neurites; Neurons; Outcome; Pattern; Positioning Attribute; Preparation; Primary Cell Cultures; Principal Investigator; Problem Solving; Process; Property; Proteins; Relative (related person); Research; Research Personnel; Role; Signal Transduction; Site; Spinal Ganglia; Surface; System; Techniques; Testing; Thick; Time; Work; aggrecan; axon growth; axon guidance; base; density; design; extracellular; immunocytochemistry; improved; in vivo; innovation; insight; interdisciplinary approach; laminin-1; multidisciplinary; nerve injury; neurite growth; neuronal cell body; polypyrrole; relating to nervous system; research study; response

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.

描述（由申请人提供）：用于神经突生长的复合生物材料项目总结：我们的长期目标是双重的：阐明在发育期间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生长促进线索的组合将使轴突生长能够克服局部抑制环境（即，神经胶质瘢痕），其在损伤后发展。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线索组合;（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指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、设计和开发来改善健康，我们的目标是将轴突生长和方向与刺激和抑制线索的特定数量和比例相关联，从而为神经再生的新策略建立基础。这项创新的多学科提案结合了主要研究者在神经元发育，再生和生物材料方面的互补专业知识以及电化学，微加工和表面表征方面的共同研究者，以制造能够提供精确数量的生物指导线索和电刺激的平台（目标1）。目标2集中于确定特定刺激引导线索（即，电刺激和层粘连蛋白-1）在增强神经突生长方面是协同的。目标3集中于确定神经突需要多少刺激来克服抑制性环境（即，硫酸软骨素蛋白聚糖）。相关性：神经在受伤后不能再生，目前的医疗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线索如何帮助神经在抑制性环境（如神经损伤部位）中生长来解决这个问题。