NEW BIOMEDICAL INTERFACE MATERIALS

心血管生物材料遭受与心血管疾病相关的众所周知的问题。 血栓和感染 表面或界面， 生物材料是决定其性能的最重要因素之一 血液相容性，或其支持生长和正常发育的能力 内皮细胞（EC）的功能。拟议的研究将侧重于 新的界面材料，旨在改善主机响应， 生物材料。 目的是开发新型仿生材料 基于非共价物理力 由细胞的糖萼产生的蛋白质是决定 被吸附蛋白质的吸附和功能状态， 随后细胞和分子相互作用。 为了验证这个假设， 我们打算研究：（1）仿生材料， EC糖萼的粘附特性和抗凝功能 旨在实现血液相容性;和（2）仿生材料 模拟细胞外基质（ECM）中的粘附糖蛋白 旨在促进内皮化。 仿生材料是 设计用于在一系列临床上- 相关的生物材料，并由表面活性剂聚合物与悬垂 寡糖、寡肽和疏水配体。 表面 修饰将通过光谱和物理表征来表征。 方法和原子力显微镜，将允许纳米成像 和分子间力的研究。 EC样抗凝剂 功能将通过悬垂肝素寡糖实现， 衍生自血栓调节蛋白的生物活性寡肽。 的影响 仿生改性对界面性质和血液的影响 相容性将从光谱、显微镜和 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 将掺入衍生自EC结合的生物活性寡肽 来自纤连蛋白的蛋白质和肝素结合寡肽。 的 粘附、生长、迁移和剪切稳定性将是 使用层流系统在生理剪切应力下测定。 细胞表面的相互作用将通过分析肌动蛋白应力来研究 纤维和粘着斑蛋白的表达。从这些 研究，我们将确定改变的机制， 界面性质影响粘附血浆蛋白和血小板 相互作用，以及这与血液相容性或 内皮化 如果成功的话，这项研究将导致 有效的仿生材料，其结合了联合收割机蛋白质抗性和 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.