SELF-ASSEMBLING GROWTH FACTOR GRADIENTS FOR NERVE REGENERATION

描述（由申请人提供）：促进大间隙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在增强神经再生方面是有效的。然而，这些材料仍然不如金标准，自体神经移植。埃尔伯特和Sakiyama-埃尔伯特的共同PI团队正在努力生产比天然再生基质上级的合成材料。合成材料将基于聚（乙二醇）（PEG），但将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。埃尔伯特实验室最近介绍了一种模块化或“自下而上”支架组装的方法，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。可以容易地改变的性质之一是微球的浮力。具有不同浮力的微球批次将在离心时自组装成分级材料。这种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。尽管已知许多用于梯度组装的技术，但是当前的方法在小直径导管中变得非常具有挑战性。新方法应被证明是更可靠和强大的生成生长因子梯度。在本项目期间，将对支架进行体外工程设计和评价，为后续项目期间的体内评价做准备。 公共卫生相关性：促进周围神经再生跨越大的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替代物已被证明在促进神经再生方面是有效的。埃尔伯特和Sakiyama-埃尔伯特的合作PI团队正在努力生产具有天然再生基质的许多特性的合成材料，以及一些上级于当前材料的特性。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。该材料将在本项目期间进一步开发，并在体外神经再生模型中进行评估。

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.