New Biomedical Interface Materials

描述（由申请人提供）： 目前的生物材料存在众所周知的问题，包括血栓形成、过度伤口愈合和感染。生物材料的表面或界面是决定这些宿主反应的最重要因素之一。拟议的研究集中在新的仿生界面材料，旨在提高主机的生物材料的反应，并基于中央的假设，控制空间放置的寡糖和/或细胞粘附肽的生物材料将促进编程的生物反应，最大限度地减少非特异性相互作用，并提高选择性细胞表面相互作用和剪切稳定的表面内皮化。建议的研究将集中在两个操作范例，“细胞表面糖萼”和“细胞外基质”（ECM），为仿生设计提供指导，并将具体研究集中在：（1）仿生材料，模拟糖萼的非粘附特性和抗凝血功能，旨在改善血液相容性;和（2）模拟ECM中粘附糖蛋白的仿生材料，其设计用于促进剪切稳定的内皮化。仿生材料在一系列临床相关的生物材料上进行表面诱导组装，并且由具有侧链寡糖、肽和疏水配体的表面活性剂聚合物组成。寡糖包括糖树枝状聚合物和瓶刷结构，其将提供致密的糖萼样界面。ECM样仿生材料结合了高亲和力的整合素结合肽和肝素蛋白聚糖结合肽，其特征在于光谱和显微技术，包括有助于定量表面配体密度和表面组装体纳米级成像的方法。将在明确定义的流动条件下通过光谱、显微镜和标记测量确定体外血液相容性。内皮细胞研究将包括使用共聚焦显微镜对肌动蛋白应力纤维和粘着斑蛋白的剪切依赖性分析。还将使用完善的猪动静脉分流模型确定血液相容性。从这些研究中，我们将确定的机制，在仿生界面的变化与血液相容性和剪切稳定内皮化。

DESCRIPTION (provided by applicant): Current biomaterials suffer from well-known problems including thrombosis, excessive wound healing, and infection. The surface, or interface, of a biomaterial is one of the most important factors that determine these host responses. The proposed studies focus on new biomimetic interface materials designed to improve host responses to biomaterials, and are based on the central hypothesis that controlled spatial placement of oligosaccharides and/or cell adhesion peptides on a biomaterial will facilitate programmed biological responses that minimize non-specific interactions, and enhance selective cell-surface interaction and shear stable surface endothelialization. Proposed research will be focused through two operational paradigms, 'cell surface glycocalyx' and 'extracellular matrix' (ECM), that provide guidance in biomimetic designs and focus specific research on: (1) Biomimetic materials that mimic the non-adhesive properties and anticoagulant function of a glycocalyx, designed to improve blood compatibility; and (2) biomimetic materials that mimic adhesive glycoproteins in the ECM designed to facilitate shear stable endothelialization. The biomimetic materials undergo surface-induced assembly on a range of clinically relevant biomaterials, and consist of surfactant polymers with pendant oligosaccharides, peptides, and hydrophobic ligands. The oligosaccharides include glycodendrimers and bottle-brush constructs that will provide a dense glycocalyx-like interface. ECM-like biomimetic materials incorporate high affinity integrin binding and heparin proteoglycan binding peptides, characterized by spectroscopic and microscopic techniques including methods to assist in the quantification of surface ligand densities and nanoscale imaging of surface assemblies. In vitro blood compatibility will be determined from spectroscopic, microscopic, and labeling measurements under well defined flow conditions. Endothelial cell studies will include shear-dependent analysis of actin stress fibers and focal adhesion proteins using confocal microscopy. Blood compatibility also will be determined using a well-established porcine a-v shunt model. From these studies, we shall determine the mechanisms by which alterations in the biomimetic interface correlates to blood compatibility and shear stable endothelialization.