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）：跨越大间隙促进周围神经再生仍然是重大的医学和工程挑战。具有生长因子和粘附因子梯度的材料已被证明可有效增强神经再生。然而，这些材料仍然不如金标准——自体神经移植物。 Elbert 和 Sakiyama-Elbert 的联合 PI 团队正在努力生产优于天然再生基质的合成材料。合成材料将以聚乙二醇（PEG）为基础，但具有纤维蛋白的许多特性。最重要的是，PEG材料将具有自组装生长因子和粘附因子梯度的新能力。 Elbert 实验室最近推出了一种模块化或“自下而上”支架组装方法，该方法使用具有不同特性的 PEG 微球在细胞存在的情况下组装支架。可以容易地改变的特性之一是微球的浮力。具有不同浮力的批次微球将在离心后自组装成分级材料。该特性将用于在用于神经引导导管的小支架中建立生长因子 GDNF 和粘附蛋白层粘连蛋白的梯度。尽管许多用于梯度组装的技术是已知的，但是当前的方法在小直径导管中变得非常具有挑战性。新方法应该被证明对于生成生长因子梯度更加可靠和稳健。支架将在本项目期间进行体外设计和评估，为后续项目期间的体内评估做好准备。 公共卫生相关性：促进周围神经再生的巨大差距仍然是重大的医学和工程挑战。生长因子和粘附因子的梯度已被证明可有效增强神经再生。 Elbert 和 Sakiyama-Elbert 的联合 PI 团队正在致力于生产合成材料，这些材料具有天然衍生的再生基质的许多特性，以及一些优于现有材料的特性。重要的是，这些材料将具有自组装生长因子和粘附因子梯度的新能力。这些材料将在该项目期间得到进一步开发，并在体外神经再生模型中进行评估。