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

ID：MPS/DMR/BMAT（7623）0906123 PI：Gopalan，Padma ORG：威斯康星大学标题：该奖项是根据2009年美国复苏和再投资法案（公法111-5）资助的。智力优势：该提案描述了一个为期三年的计划，该计划将在生物材料平台上进行综合研究，教育和推广，以研究人类间充质干细胞（hMSCs）。建议开发模型平台，该平台将允许在延长的时间范围内稳定呈现细胞粘附基序，以清楚地解决假设：ECM衍生的细胞粘附配体强烈影响成骨hMSC分化。用于研究细胞相互作用的合成模板应满足多个要求，例如：（a）在生物惰性背景上以优化的组合呈现多个信号，这需要合成灵活性，（B）应用于一系列平面和非平面基底的能力，（c）对于长分化细胞在延长的时间段内的稳定性，和（d）空间定位信号的能力。最后两项要求将模板的适用性扩展到生物医学植入物和器械。将检查具有2- 3%交联的UV交联薄膜（30- 50 nm）。 拟议的研究的智力影响是在利用交联薄膜的属性，如特殊的稳定性，应用于非典型基板，化学tailorability是cytophobic或cytophilic，和photo-patternability研究长分化过程。 为实现这一目标将开展的具体任务是：（a）材料合成一系列基于聚乙二醇共聚物的可紫外线交联共聚物，其中含有可光交联和配体（生物信号）基团的受控分布。 (b)通过表面表征方法和荧光团标记肽的组合评估模板的机械和化学稳定性。 (c)研究细胞在标准细胞培养基和含成骨添加剂的细胞培养基中的粘附、生长和分化。 (d)通过浸涂、微接触印刷和使用超声波显微镜，改进各种非平面基材的方法。更广泛的影响：该提案的更广泛影响将是开发一类新的生物材料涂层，具有用于干细胞研究的独特特性。为了清楚地了解微环境信号对干细胞行为的影响，迫切需要向干细胞呈现特定信号和复杂信号组合的实验系统。最终，这一系列的研究可能会导致识别促进谱系特异性干细胞分化的信号，从而开发和优化促进体外和体内干细胞分化的底物。PI和co-Pi还建议通过两门课程引入跨学科课程开发，即基于材料科学工程的聚合物材料和基于生物医学工程的干细胞生物工程。正在进行的教育推广到K-12水平将继续开发实践展览，用于学校环境，特别注意匹配威斯康星州的K-12科学标准。 PI和co-PI将指导女性和代表性不足的研究生和本科生在他们的研究实验室。

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.