NANO STRUCTURED BIOMIMETIC BIOMATERIALS

纳米结构仿生生物材料

• 批准号: 2750520
• 负责人: Steven L. Goodman
• 金额: $ 10.34万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-01 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2750520
• 关键词: artery; biomaterial development /preparation; cardiovascular prosthesis; cell adhesion; cell differentiation; extracellular matrix; gene expression; homeostasis; mechanical stress; phenotype; surface property; synthetic protein; tissue /cell culture; vascular endothelium; veins

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.

描述：(改编自调查人员摘要)在开发中 生物学上，三维力被认为是至关重要的 在组织分化中很重要。目前的体外研究表明 作用在单个细胞上的微机械作用力与 对它们的表型分化很重要。由于内皮细胞在 活体是由内皮下的纳米-微米结构支撑的 细胞外基质(ECM)，作用于其上的微机械作用力 这些细胞也必须在这个纳米尺度上发挥作用。调查这一角色 这些微机械作用力是困难的，因为ECM不仅是 结构复杂，但还含有多种蛋白质和其他生物活性 选民。这项建议的中心目标是审查 使用3-D合成聚合物复制品的ECM拓扑学研究细胞行为 这个高度复杂的表面。复制品是用失落的蜡样制作的 提供大分子精确度的铸造技术。因为他们可能是 完全人工合成，这允许在实验中分离 结构--来自作用于细胞的生化影响的机械。它 假设复制ECM的3-D合成血管假体 纳米尺度将有助于改善细胞分化，因此 内皮化假体的抗血栓特性。第一个目标 是系统地研究ECM在血管中的解剖变异 在施加给内皮细胞的机械应力上有很大的差异， 包括不同直径、不同流动条件(剪切、 脉动性、湍流)和顺应性。这将使您能够深入了解 体内基质形态的作用，并可用于指导选择 不同血管生物材料适宜的基质形态 申请。解剖研究将使用ECM复制品，因为这些允许 精细结构的大分子水平分析，同时也保留了 与大体血管解剖不同的是，精细结构的定向 传统的显微镜方法。这也将允许对ECM的研究 例如，停滞区和湍流区的形态 分叉。这些研究的第二个方面将检查内皮细胞 细胞附着在不同形态的基质复制品上，在两种静态条件下 和剪切条件。评估将检查电池的机械方面 黏附(细胞骨架结构、整合素受体表达和 位置)，以及表型分化的标记、基因表达和 抗血栓特性(CFO、各种RNA、前列环素产生、 血小板相互作用)来阐明基质形态的相对作用 以及剪切力对内皮细胞行为的影响。