Surface Engineering Strategies for Studying Human Mesenchymal Stem Cells (hMSCs).

研究人类间充质干细胞 (hMSC) 的表面工程策略。

• 批准号: 0906123
• 负责人: Padma Gopalan
• 金额: $ 32.5万
• 依托单位: University of Wisconsin-Madison
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0906123&HistoricalAwards=false
• 关键词: Surface; Engineering; Strategies; Studying; Human

ID: MPS/DMR/BMAT(7623) 0906123 PI: Gopalan, Padma ORG: University of WisconsinTitle: Surface Engineering Strategies for Studying Human Mesenchymal Stem Cells (hMSCs)This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).INTELLECTUAL MERIT: This proposal describes a three-year plan of integrated research, education, and outreach on a biomaterial platform for studying human mesenchymal stem cells (hMSCs). It is proposed to develop model platforms that will allow for stable presentation of cell adhesion motifs over an extended time frame, to clearly address the hypothesis: ECM-derived cell adhesion ligands strongly influence osteogenic hMSC differentiation. The synthetic templates for studying cellular interactions, should meet multiple requirements such as: (a) presentation of multiple signals in optimized combinations on a bioinert background, which requires synthetic flexibility, (b) ability to apply to a range of planar and non-planar substrates, (c) stability over extended time period for long differentiating cells, and (d) the ability to spatially localize the signals. The last two requirements would extend the applicability of the template to biomedical implants and devices. UV-crosslinked thin-films (30-50nm) with 2-3 % of crosslinking will be examined. The intellectual impact of the proposed research is in exploiting the attributes of crosslinked thin-films such as exceptional stability, application to atypical substrates, chemical tailorability to be cytophobic or cytophilic, and photo-patternability for studying long differentiation processes. The specific tasks that will be undertaken towards this goal are: (a) Materials synthesis of a range of UV-crosslinkable copolymers based on polyethylene glycol copolymers containing a controlled distribution of photo-crosslinkable and ligand (biological signals) groups. (b) Evaluation of mechanical and chemical stability of the templates by a combination of surface characterization methods and fluorophore tagged peptides. (c) Study the cell adhesion, growth and differentiation in standard cell culture medium and cell culture medium containing pro-osteogenic supplements. (d) Evolve methodology to modify a variety of non planar substrates by dipcoating, microcontact printing and use of an ultrasonic microplotter. BROADER IMPACTS: The broader impact of the proposal will be developing a new class of biomaterials coatings with unique set of properties for stem cell studies. In order to clearly understand the effects of microenvironmental signals on stem cell behavior, there is a critical need for experimental systems that present specific signals, and complex signal combinations, to stem cells. Ultimately, this line of research may result in identification of signals that promote lineage-specific stem cell differentiation, leading to development and optimization of substrates that promote stem cell differentiation in vitro and in vivo. The PI and co-Pi also propose to introduce interdisciplinary curriculum development through two courses, Polymeric Materials, based in Materials Science & Engineering, and Stem Cell Bioengineering, based in Biomedical Engineering. Ongoing educational outreach to the K-12 level will continue to develop hands-on exhibits for use in school settings with special attention to matching the K-12 Science Standards of the State of Wisconsin. The PI and co-PI will mentor female and underrepresented graduate and undergraduate students in their research laboratories.

同上：MPS/DMR/BMAT（7623）0906123 PI：GOPALAN，PADMA ORG：威斯康星大学：研究人类间充质干细胞（HMSC）的表面工程策略（HMSC）该奖项在2009年的2009年（公共法律111-5）中介绍了美国恢复和重新计划。教育和在研究人间充质干细胞（HMSC）的生物材料平台上进行宣传。提议开发模型平台，以允许在延长的时间范围内稳定地呈现细胞粘附基序，以清楚地解决该假设：ECM衍生的细胞粘附配体强烈影响成骨的HMSC分化。用于研究细胞相互作用的合成模板应满足多种要求，例如：（a）在生物渗透背景上进行优化组合中多个信号的呈现，这需要合成的灵活性，（b）能够应用于平面和非平面底物的范围的能力，（c）长期分化的符号范围的稳定性稳定的稳定性，并且（c）符号分化的能力分别分配和（d）分散的（d）。最后两个要求将将模板的适用性扩展到生物医学植入物和设备上。将检查与2-3％的交联的紫外线薄膜（30-50nm）。 拟议研究的智力影响在于利用交联薄膜的属性，例如特殊的稳定性，对非典型底物的应用，化学可调节性的细胞恐惧症或细胞粒细胞，以及用于研究长分化过程的照片触发性。 将实现该目标的特定任务是：（a）基于基于聚乙烯甘氨基共聚物的一系列紫外线链接共聚物的材料，这些共聚物含有可控分布的光链接和配体信号（生物信号）组。 （b）通过表面表征方法和荧光团标记的肽的组合评估模板的机械和化学稳定性。 （C）研究标准细胞培养基培养基和含有促染色体补充剂的细胞培养基和细胞培养基的细胞粘附，生长和分化。 （d）进化方法来通过二涂层，微接合印刷和使用超声波微块球来修改各种非平面底物。更广泛的影响：该提案的更广泛影响将开发一类新的生物材料涂层，具有独特的干细胞研究特性。为了清楚地了解微环境信号对干细胞行为的影响，对呈现特定信号和复杂信号组合的实验系统至关重要。最终，这一研究可能会导致鉴定促进谱系特异性干细胞分化的信号，从而导致促进体外和体内干细胞分化的底物的发展和优化。 PI和Co-Pi还建议通过基于生物医学工程的两种课程，基于材料科学与工程的聚合物材料以及干细胞生物工程来引入跨学科课程开发。与K-12级别的持续教育宣传将继续开发动手展览，以在学校环境中使用，特别注意与威斯康星州的K-12科学标准相匹配。 PI和Co-Pi将在其研究实验室中指导女性和代表性不足的研究生和本科生。