Substrate Independent, Spatially Resolved, Stable Polymer Coatings for Studying Human Mesenchymal Stem Cells (hMSCs)

用于研究人间充质干细胞 (hMSC) 的基底独立、空间分辨、稳定的聚合物涂层

• 批准号: 1306482
• 负责人: Padma Gopalan
• 金额: $ 39万
• 依托单位: University of Wisconsin-Madison
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2018-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1306482&HistoricalAwards=false
• 关键词: Substrate; Independent; Spatially; Resolved; Stable

This award by the Biomaterials program in the Division of Materials Research is a three-year plan of integrated research, education, and outreach on a polymeric coating for studying human mesenchymal stem cells (hMSCs). This award is cofunded by the Polymer program in the Division of Materials Research. Earlier studies strongly indicate that hMSC phenotype is strongly influenced by ligands derived from the natural cellular microenvironment, including cell adhesion peptides, heparin-binding peptides, and growth factor-mimetic peptides. This proposal is to develop polymer coatings based on copolymers of poly(ethylene glycol) with at most 10% of crosslinkable groups, which can be crosslinked into 30 nm mats for immobilization of peptides. These mats are chemically-defined for stable presentation of two putative pro-osteogenic peptides over an extended timeframe, and to explore in depth the effects on hMSC differentiation into osteoblasts. These polymer coatings with peptides present a stable cytophobic slate, and hence one can truly investigate the effect of the relevant peptides on hMSCs during the entire time course of osteogenic differentiation. Importantly, these coatings are thin films that can be applied to virtually any underlying substrate, which will lead to broad impact on cell culture studies and future design of biomedical devices. Because of the thin-film nature, the proposed use of X-ray photoelectron spectroscopy will quantify precisely the peptides presented on the polymer coatings. Further, this proposal will study the first systematic analysis of chemically defined, nanometer-scale presentation of a growth factor-receptor binding ligand, and it may lead to broad impact in view of the importance of receptor dimerization/clustering in virtually all growth factor signaling systems. The technological broader impact of this proposal would be in developing a new class of ultra-thin biomaterial coatings with unique set of properties for stem cell growth. In order to clearly understand the effects of micro environmental signals on stem cell behavior, there is a critical need for experimental systems that present specific signals, and complex signal combinations, to stem cells. The proposed platform may lead to widespread use of the proposed approaches by cell biologists in general. Ultimately, this line of research could 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. More generally, the proposed adaptable and chemically tailorable thin films would be applicable to a broad range of fundamental questions in cell biology in which stable, controlled presentation of peptide ligands is desirable. As part of this grant, this project will: 1) develop Interdisciplinary Curriculum Development of two courses in two departments, one based in Materials Science & Engineering, and the second one based in Biomedical Engineering; 2) carry out dissemination and outreach activities by the development of hands-on exhibits on Stem Cells and Tissue Engineering that would provide case study materials for a Science and Social Media course; and 3) recruit and mentor female and underrepresented minority graduate and undergraduate students in research activities.

生物材料研究部生物材料计划的奖项是针对研究人类间充质干细胞（HMSC）的聚合物涂层综合研究，教育和外展的三年计划。该奖项是由材料研究部的聚合物计划获得的。早期的研究强烈表明，HMSC表型受到源自天然细胞微环境的配体的强烈影响，包括细胞粘附肽，肝素结合肽和生长因子模拟肽。该建议是基于聚合物涂料基于聚合物（乙二醇）的共聚物，最多可与10％的交联基团开发，可以将其交联成30 nm MATS以固定肽。 这些垫子是化学定义的，可在延长的时间范围内稳定地呈现两个推定的促稳态肽，并深入探索对HMSC分化成骨细胞的影响。这些与肽的聚合物涂层具有稳定的细胞质板，因此可以在整个成骨分化的过程中真正研究相关肽对HMSC的影响。重要的是，这些涂层是薄膜，几乎可以应用于任何潜在的底物，这将对细胞培养研究和生物医学设备的未来设计产生广泛的影响。由于具有薄膜的性质，因此提出的X射线光电子光谱法将精确地量化聚合物涂层上呈现的肽。此外，该提案将研究对生长因子受体结合配体的化学定义，纳米尺度呈现的首次系统分析，并且鉴于受体二聚体/聚类在几乎所有生长因子信号系统中的重要性，它可能会导致广泛的影响。该提案的技术更广泛的影响是开发新的一类新的超薄生物材料涂层，并具有独特的干细胞生长特性。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。所提出的平台可能会导致细胞生物学家通常广泛使用所提出的方法。最终，这一研究可能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。更普遍地，提出的适应性和化学量身定制的薄膜将适用于细胞生物学中的广泛基本问题，其中稳定，受控的肽配体的表现是可取的。作为这笔赠款的一部分，该项目将：1）开发两个部门的两个课程的跨学科课程开发，一个基于材料科学和工程，第二个基于生物医学工程的课程； 2）通过开发有关干细胞和组织工程的动手展览来进行传播和外展活动，这些展览将为科学和社交媒体课程提供案例研究材料； 3）招募和导师的女性和代表性不足的少数群体研究生和本科生从事研究活动。