NANO STRUCTURED BIOMIMETIC BIOMATERIALS

描述：（改编自研究者摘要）在发育中 据了解，三维力是至关重要的 在组织分化中起重要作用。 体外研究表明 作用在单个细胞上的微机械力 对它们的表型分化很重要。 由于内皮细胞在 由内皮下的纳米-微米结构支持 细胞外基质（ECM），作用于细胞外基质的微机械力， 这些细胞也必须在这种纳米尺度下发挥作用。 调查角色 这些微机械力是困难的，因为ECM不仅 结构复杂，但也含有多种蛋白质和其它生物活性物质 选民。 这项建议的主要目的是审查 使用3-D合成聚合物复制品对细胞行为的ECM形貌 这个高度复杂的表面。 复制品是用一种类似蜡的东西制作的 铸造技术提供高分子精度。 因为它们可以 完全合成，这允许实验分离的 结构机械的生化影响作用于细胞。 它 假设复制ECM的3D人造血管假体 纳米尺度将有助于改善细胞分化， 内皮化假体的抗血栓性质。 第一个目标 是系统地研究血管中的ECM解剖变异， 内皮细胞上的机械应力变化很大， 包括不同直径的动脉和静脉，流动条件（剪切， 脉动性、湍流）和顺应性。 这将提供深入了解 基质形态的体内作用，并可用于指导选择 适用于不同血管生物材料的基质形态 应用. 解剖学研究将使用ECM复制品，因为这些复制品允许 精细结构的大分子水平分析，同时还保留了 精细结构与大体血管解剖结构的定位，不像 常规显微镜方法。 这也将允许研究ECM 例如，在停滞和湍流区域中的形态， 分叉 这些研究的第二个方面将检查内皮细胞 细胞粘附到不同形态的基质复制品上，在两种静态 和剪切条件。 评估将检查细胞的机械方面 粘附（细胞骨架结构，整合素受体表达和 位置），以及表型分化、基因表达和 抗血栓形成特性（cFOS，各种mRNA，前列环素产生， 血小板相互作用），以阐明基质形态的相对作用 和剪切应力对内皮细胞行为的影响。

DESCRIPTION: (Adapted from investigator's abstract) In developmental biology it is understood that three-dimensional forces are critically important in tissue differentiation. In vitro investigations now suggest that micro-mechanical forces acting upon individual cells are equally as important for their phenotypic differentiation. Since endothelial cells in vivo are supported by the nanometer-micron structure of the subendothelial extracellular matrix (ECM), the micro- mechanical forces which act upon these cells must also be exerted at this nanoscale. Investigating the role of these micro-mechanical forces is difficult since ECMs are not only structurally complex but also contain multiple proteins and other bioactive constituents. The central aim of this proposal is to examine the effect of ECM topography on cell behavior using 3-D synthetic polymeric replicas of this highly complex surface. Replicas are produced using a lost-wax-like casting technique providing macromolecular accuracy. Since they may be entirely synthetic, this permits experimental separation of the structural-mechanical from the biochemical influences acting upon cells. It hypothesized that 3-D synthetic vascular prosthetics which replicate the ECM nano- scale will be useful in improving cellular differentiation and hence the antithrombotic properties of endothelialized prosthetics. The first aim is to systematically investigate ECM anatomical variations in vessels which vary greatly in the mechanical stresses placed upon endothelial cells, including arteries and veins of differing diameters, flow conditions (shear, pulsatility, turbulence) and compliance. This will provide insight into the in vivo role of matrix morphology and can serve to guide choices for the appropriate matrix morphology for different vascular biomaterial applications. Anatomical studies will use ECM replicas since these permit macromolecular level analysis of fine structure while also preserving the orientation of fine structure with gross vascular anatomy, unlike conventional microscopic methods. This will also permit study of ECM morphology in, for example, regions of stasis and turbulence at bifurcations. The second aspect of these studies will examine endothelial cells adherent to matrix replicas of differing morphology, under both static and shear conditions. Evaluations will examine mechanical aspects of cell adhesion (cytoskeletal structure, integrin receptor expression and location), and markers of phenotypic differentiation, gene expression, and antithrombotic properties (cFOS, various mRNAs, prostacyclin production, platelet interaction) to elucidate the relative role of matrix morphology and shear stresses on endothelial cell behavior.