SELF-ASSEMBLING GROWTH FACTOR GRADIENTS FOR NERVE REGENERATION

描述(由申请人提供)：促进周围神经再生跨越巨大的缺口仍然是一个巨大的医学和工程挑战。含有生长因子和黏附因子梯度的材料已被证明在促进神经再生方面是有效的。然而，这些材料仍然低于金标准--自体神经移植。Elbert和Sakiyama-Elbert的共同PI团队正在领导一项努力，以生产出优于自然衍生再生基质的合成材料。合成材料将以聚乙二醇酯(PEG)为基础，但将具有纤维蛋白的许多特性。最重要的是，聚乙二醇材料将具有自组装生长因子和黏附因子梯度的新能力。埃尔伯特实验室最近推出了一种模块化或自下而上的支架组装方法，它使用具有不同性质的聚乙二醇微球在细胞存在的情况下组装支架。微球的浮力是易于修改的性质之一。一批批具有不同浮力的微球在离心后会自组装成一种梯度材料。这一特性将被用来在用于神经引导管道的小支架中建立生长因子GDNF和黏附蛋白LN的梯度。尽管已知许多用于梯度组装的技术，但当前的方法在小直径管道中变得非常具有挑战性。新的方法应该被证明是更可靠和更稳健的增长因子梯度生成方法。支架将在本项目期间进行工程设计和体外评估，为后续项目期间的体内评估做准备。 与公共卫生相关：促进周围神经再生跨越巨大差距仍然是重大的医学和工程挑战。生长因子和黏附因子的梯度已被证明在促进神经再生方面有效。Elbert和Sakiyama-Elbert的共同PI团队正在领导一项努力，以生产具有自然衍生再生基质的许多特性，以及一些优于现有材料的特性的合成材料。重要的是，这些材料将具有自组装生长因子和黏附因子梯度的新能力。这些材料将在本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。

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.