SELF-ASSEMBLING GROWTH FACTOR GRADIENTS FOR NERVE REGENERATION

用于神经再生的自组装生长因子梯度

• 批准号: 8258036
• 负责人: DONALD L ELBERT
• 金额: $ 22.8万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-15 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8258036
• 关键词: 3-Dimensional; Adhesions; Affinity; Azides; Caliber; Cell Adhesion; Cell Adhesion Molecules; Cell Culture Techniques; Cells; Centrifugation; Chemistry; Collaborations; Complex; Development; Engineering; Ensure; Ethylene Glycols; Evaluation; Extracellular Matrix; Fiber; Fibrin; Gold; Growth; Growth Factor; Human; Hydrogels; In Vitro; Inferior; Laminin; Medical; Methods; Microspheres; Modeling; Motor; Natural regeneration; Nerve; Nerve Regeneration; Neurites; Neuroglia; Organic solvent product; Peripheral Nerves; Phase; Plasmin; Preparation; Process; Production; Property; Proteins; Reaction; Solutions; Structure; System; Techniques; Testing; Tubular formation; analog; aqueous; base; crosslink; ethylene glycol; in vitro Model; in vivo; innovation; nerve autograft; neurotrophic factor; novel; polymerization; relating to nervous system; scaffold; self assembly; surfactant

DESCRIPTION (provided by applicant): Promotion of peripheral nerve regeneration across large gaps continues to be substantial medical and engineering challenge. Materials with gradients of growth factors and adhesion factors have proven to be effective in enhancing nerve regeneration. However, these materials are still inferior to the gold standard, nerve autograft. The co-PI team of Elbert and Sakiyama- Elbert are leading an effort to produce synthetic materials that are superior to naturally derived regeneration matrices. The synthetic materials will be based on poly(ethylene glycol) (PEG) but will have many of the properties of fibrin. Most importantly, the PEG materials will have the novel ability to self-assemble gradients of growth factors and adhesion factors. The Elbert lab recently introduced a method of modular or 'bottom-up' scaffold assembly that uses PEG microspheres with different properties to assemble scaffolds in the presence of cells. One of the properties that can be easily modified is the buoyancy of the microspheres. Batches of microspheres with different buoyancies will self-assemble into a graded material upon centrifugation. This property will be used to establish gradients of the growth factor GDNF and the adhesion protein laminin in small scaffolds that are used for nerve guidance conduits. Although many techniques for gradient assembly are known, current methods become very challenging in small diameter conduits. The new method should prove to be more reliable and robust for generating growth factor gradients. The scaffolds will be engineered and evaluated in vitro in this project period in preparation for in vivo evaluation in subsequent project periods. PUBLIC HEALTH RELEVANCE: Promotion of peripheral nerve regeneration across large gaps continues to be substantial medical and engineering challenge. Gradients of growth factors and adhesion factors have proven to be effective in enhancing nerve regeneration. The co-PI team of Elbert and Sakiyama-Elbert are leading an effort to produce synthetic materials that have many of the properties of naturally derived regeneration matrices, and some properties that are superior to current materials. Importantly, the materials will have the novel ability to self-assemble gradients of growth factors and adhesion factors. The materials will be further developed in this project period and evaluated in an in vitro model of nerve regeneration.

描述（由申请人提供）：促进跨大差距的周围神经再生仍然是实质性的医学和工程挑战。具有生长因子和粘附因子梯度的材料已被证明有效增强神经再生。但是，这些材料仍然不如金标准神经自体移植。 Elbert和Sakiyama- Elbert的Co-Pi团队正在努力生产出优于自然衍生的再生矩阵的合成材料。合成材料将基于聚乙二醇（PEG），但具有许多纤维蛋白的特性。最重要的是，PEG材料将具有新型的生长因子和粘附因子梯度的能力。 Elbert Lab最近引入了一种模块化或“自下而上”支架组件的方法，该方法使用具有不同特性的PEG微球在存在细胞的情况下组装支架。很容易修改的特性之一是微球的浮力。离心后，具有不同浮力的微球会自组装成渐变的材料。该特性将用于建立生长因子GDNF的梯度和用于神经引导导管的小脚手架中的粘附蛋白层粘连蛋白。尽管已知许多用于梯度组装的技术，但当前方法在小直径导管中变得非常具有挑战性。新方法应证明对生成生长因子梯度更可靠和强大。脚手架将在本项目期间进行工程和评估，以准备在随后的项目期间进行体内评估。 公共卫生相关性：促进大差距跨外周神经再生的挑战仍然是重大的医学和工程挑战。事实证明，生长因子和粘附因子的梯度有效增强神经再生。 Elbert和Sakiyama-Elbert的Co-Pi团队正在努力生产具有自然衍生的再生矩阵的许多特性的合成材料，并且某些特性比当前材料优于当前材料。重要的是，这些材料将具有新颖的能力来自组成生长因子和粘附因子的梯度。这些材料将在该项目期间进一步开发，并在神经再生的体外模型中进行评估。