NEW BIOMEDICAL INTERFACE MATERIALS

心血管生物材料面临着众所周知的相关问题 血栓形成和感染。对象的表面或界面 生物材料是决定其性能的最重要的因素之一 血液相容性，或其支持生长和正常的能力 内皮细胞(EC)的功能。拟议的研究将集中于 新的接口材料旨在提高宿主对 生物材料。目标是开发新的仿生材料 基于非共价物理力的中心假设 由细胞的糖基化所产生的主要决定因素 被吸附的蛋白质的吸附和功能状态，这控制着 随后的细胞和分子相互作用。为了检验这一假设， 我们打算研究：(1)仿生材料模仿非 EC糖萼的粘附性和抗凝血功能 用于实现血液相容性的设计；以及(2)仿生材料 在细胞外基质(ECM)中模拟粘附性糖蛋白 旨在促进内皮化。仿生材料是 设计成在一系列临床上进行不可逆转的组装- 相关生物材料，由表面活性聚合物和悬挂物组成 低聚糖、寡肽和疏水配体。表面 修饰将通过光谱和物理手段来表征 方法和原子力显微镜，将允许纳米级成像 以及分子间作用力的检验。类EC抗凝剂 功能将通过悬挂的肝素低聚糖和 血栓调节蛋白衍生的生物活性寡肽。的影响 界面性质和血液的仿生修饰 兼容性将通过光谱、显微和 蛋白质和血小板-表面相互作用的标记测量 明确的动态流动条件。类ECM仿生材料 将结合来自EC结合的生物活性寡肽 纤维连接蛋白中的蛋白质和肝素结合寡肽。这个 人内皮细胞的黏附、生长、迁移和剪切稳定性 在生理剪应力下使用层流系统测定。 将通过分析肌动蛋白应力来研究细胞-表面的相互作用 纤维和焦点黏附蛋白的共聚焦显微镜观察。从这些 研究，我们将确定改变的机制，在 界面性质对黏附血浆蛋白和血小板的影响 相互作用，以及这与血液相容性或 内皮化。如果成功，这项研究将导致高度 有效的仿生材料结合了蛋白质抗性和 抗凝功能；或促进稳定的内皮化。

Cardiovascular biomaterials suffer from well-known problems associated with thrombosis and infection. The surface, or interface, of a biomaterial is one of the most important factors that determines its blood compatibility, or its ability to support growth and normal function of endothelial cells (EC). The proposed studies will focus on new interface materials designed to improve the host response to biomaterials. The objectives are to develop new biomimetic materials based on the central hypothesis that non-covalent physical forces created by a cell's glycocalyx provides the major determining factor in the adsorption and functional state of adsorbed proteins, that controls subsequent cell and molecular interactions. To test this hypothesis, we propose to investigate: (1) Biomimetic materials that mimick non- adhesive properties and anticoagulant functions of EC glycocalyx designed to achieve blood compatibility; and (2) biomimetic materials that mimick adhesive glycoproteins in the extracellular matrix (ECM) designed to facilitate endothelization. The biomimetic materials are designed to undergo irreversible assembly on a range of clinically- relevant biomaterials, and consist of surfactant polymers with pendant oligosaccharides, oligopeptides, and hydrophobic ligands. Surface modifications will be characterized by spectroscopic and physical methods, and atomic force microscopy that will permit nanoscale imaging and examination of intermolecular forces. EC-like anticoagulant functions will be achieved through pendant heparin oligosaccharides and bioactive oligopeptides derived from thrombomodulin. The effect of biomimetic modifications on interfacial properties and blood compatibility will be determined from spectroscopic, microscopic, and labeling measurements of protein and platelet-surface interactions under well-defined dynamic flow conditions. ECM-like biomimetic materials will incorporate bioactive oligopeptides derived from EC binding proteins and heparin binding oligopeptides from fibronectin. The adhesion, growth, migration, and shear stability of human ECs will be determined using a laminar flow system at physiologic shear stresses. Cell-surface interactions will be studied by analysis of actin stress fibers and focal adhesion proteins using confocal microscopy. From these studies, we shall determine the mechanisms by which alteration in interfacial properties affects adhesive plasma protein and platelet interactions, and how this correlates to blood compatibility or endothelization. If successful, this research will lead to highly effective biomimetic materials that combine protein resistance and anticoagulant functions; or facilitate stable endothelization.