Carbon Nanotubes Impregnated with Stem Cells to Return Motor Skills

该奖项是根据2009年《美国复苏和再投资法》(公法111-5)资助的。“PI：韦伯斯特，托马斯岛，建议编号：0730906需要新材料来恢复残疾人的功能，因为目前的材料还不够。纳米技术的广义定义是使用至少一维小于100纳米的材料(所谓的纳米材料)，它已经开始给科学和工程领域带来革命性的变化；但到目前为止，医学应用还没有广泛受益于纳米材料的使用。特别是，尽管前景看好，但一种特殊的纳米材料(碳纳米管)在修复受损的神经组织和恢复残疾人功能方面有很大的希望。与干细胞相结合的碳纳米管在修复受损神经组织方面具有耐人寻味的纳米材料，因为它们能够：(I)当被植入大脑的受损非导电区域时导电，(Ii)模拟神经组织中发现的关键蛋白质(如层粘连蛋白)的纳米特征，以促进干细胞分化，提高神经元功能并减少胶质疤痕组织的形成，以及(Iii)将干细胞锚定在大脑的受损区域，以阻止干细胞迁移出大脑最需要它们的部分。这项提议将研究碳纳米管传递、锚定和促进干细胞分化为神经元的能力，以修复和重建受损神经组织的电导率；恢复残疾人运动功能的关键标准。因此，本研究的具体目的是：(I)确定促进干细胞黏附和分化为神经元的碳纳米管化学功能化策略，(Ii)进行体外分析，以确定促进干细胞向神经元分化的最佳碳纳米管功能化策略，同时降低胶质瘢痕组织细胞功能，以及(Iii)确定通过体外实验发现的最佳碳纳米管功能化策略在已建立的大鼠短暂性脑缺血模型中修复中风引起的神经组织损伤的能力。这一提议的智力价值在于，它将迈出大胆的一步，开发出纳米技术衍生的材料，这种材料可以锚定并刺激干细胞分化为神经元，以修复受损的神经组织，恢复残疾人的功能。这项提议的广泛影响是，它将激励K-12、本科生和研究生学习纳米技术如何被用于治疗各种疾病。为此，将把这项计划中的本科生和研究生纳入：i)布朗大学新授予的G，K？12网站(该网站将布朗大学的学生分配到普罗维登斯少数族裔公立学校，以激励学习者学习科学、技术、工程和数学(STEM))；ii)布朗大学的脑科学项目(有许多外展活动)；以及(Iii)由NSF资助的布朗大学MRSEC网站(通过REU网站吸收了许多本科生)。这项建议还通过延世大学顾问的合作进行了强有力的国际合作，将交流许多学生和想法，以加强各自机构的纳米技术在医学方面的教育。

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5)."PI: Webster, ThomasProposal Number: 0730906Novel materials are needed to restore functions to persons with disabilities since current materials have not sufficed. Nanotechnology, broadly defined as the use of materials with at least one dimension less than 100 nm (so called nanophase materials), have begun to revolutionize the fields of science and engineering; but as of yet, medical applications have not yet widely benefited from the use of nanomaterials. In particular, despite promise, one particular nanomaterial (carbon nanotubes) holds much promise to heal damaged neural tissue and restore functions to disabled persons. Carbon nanotubes coupled with stem cells are intriguing nanomaterials to heal damaged neural tissue due to their ability to: (i) conduct electricity when implanted into damaged, non-conductive, regions of the brain, (ii) mimic the nanometer features of key proteins found in neural tissue (such as laminin) to favor stem cell differentiation, increase neuron functions and decrease glial scar tissue formation, and (iii) anchor stem cells into damaged regions of the brain to inhibit stem cells from migrating away from the part of the brain in which they are needed most. This proposal will investigate the ability of carbon nanotubes to deliver, anchor, and promote stem cell differentiation into neurons to heal and reestablish electrical conductivity in damaged neural tissue; critical criteria to return motor functions to disabled persons. Thus, the specific aims of this study are to: (i) determine carbon nanotube chemical functionalization strategies that promote stem cell adhesion and differentiation into neurons, (ii) conduct in vitro analysis to determine the best carbon nanotube functionalization strategies that promote stem cell differentiation into neurons while at the same time decrease glial scar tissue cell function, and (iii) determine the ability of the best carbon nanotube functionalization strategies found through in vitro assays to heal stroke-induced neural tissue damage in a well-established rat transient cerebral ischemia model. This intellectual merit of this proposal is that it will take a bold step to formulate nanotechnology-derived materials that can anchor and stimulate stem cell differentiation into neurons to heal damaged neural tissue and restore function to disabled persons. The broad impacts of this proposal is that it will motivate K-12, undergraduate and graduate minority students to learn how nanotechnology is being used to treat various illnesses. This will be done by incorporating undergraduate and graduate students from this proposal into: i) a newly awarded G, K ? 12 site at Brown University (which places Brown students into minority Providence public schools to motive learners to study science, technology, engineering, and math (STEM)); ii) the Brain Science Program at Brown (which has numerous outreach activities); and (iii) the NSF funded MRSEC site at Brown University (which incorporates numerous undergraduates through REU sites). This proposal also has a strong international collaboration through the cooperation of the consultant from Yonsei University in which numerous students and ideas will be exchanged to strengthen educational aspects of nanotechnology in medicine at respective institutions.