SCREENING PLATELETS INTERACTIONS WITH SURFACE GRADIENTS

筛选血小板与表面梯度的相互作用

基本信息

批准号：
7629738
负责人：
VLADIMIR HLADY
金额：
$ 21.77万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
1990
资助国家：
美国
起止时间：
1990-04-01 至 2011-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7629738
关键词：
Adhesions Affinity Binding Binding Proteins Biocompatible Materials Blood Blood Platelets Blood Proteins Charge Chemistry Databases Deposition Development Elements Engineering Environment Etiology Event Fibrinogen Fibronectins Friction Funding Grant Image Immune response In Situ Knowledge Lead Length Manuscripts Maps Measures Mediating Membrane Proteins Methodology Modeling Molecular Molecular Structure Muscle Rigidity Organism Outcome Paper Pattern Phase Plasma Plasma Proteins Platelet Activation Polymers Positioning Attribute Progress Reports Property Protein Binding Proteins PubMed Publishing Reaction Research Research Personnel Resolution Resources Science Screening procedure Serum Serum Albumin Solutions Structure Surface Surface Properties Techniques Testing Time base biomaterial compatibility biomaterial interface density design electrical potential interfacial nano nanometer nanoscale novel physical state programs protein distribution research study skills tool

项目摘要

DESCRIPTION (provided by applicant): SCREENING PLATELETS INTERACTIONS WITH SURFACE GRADIENTS Most biomaterials become coated with a protein layer within seconds after being exposed to a protein-containing environment such as blood. It is generally accepted that the protein layer build-up at the biomaterial - host interface is largely responsible for the host's reactions to the biomaterial. We propose designing new types of surface gradients to understand how different combinations of surface parameters mediate ad-layers of blood proteins and subsequent platelet interactions. We anticipate that the knowledge gained in the proposed research will lead us closer to truly hemocompatible biomaterials. The general aims of the proposed research are to: engineer new biomaterial interfaces with controlled surface gradients of selected molecular parameters, and use them to test for platelet adhesion and activation after they've acquired a protein layer from blood. We propose to design the following spatial gradients: - gradient of hydrophobic and hydrophilic nano-domains, - gradient of surface charges and dipoles, and - gradient of surface density of hydrophilic polymers with different chain rigidity. We will study the effects that each of the gradient parameters have on: (i) affinity towards adsorbing proteins from blood plasma or serum, (ii) distribution, dynamics and mobility of adsorbed blood proteins, and (iii) adhesion and activation of platelets. The use of spatially controlled molecular gradients will enable us to rapidly pre-screen the effect(s) that a given magnitude and the combination of surface properties has on blood protein binding and platelet adhesion and activation. The pre-screening phase will be followed by a transposition of a particular local gradient region at which we found minimal platelet adhesion into a uniform, non-gradient version of the same surface molecular structure which will be re- tested for the same effect. The novelty in our approach is in the parallelism that is built-in in the molecular gradient approach. By using gradients of several key surface parameters and correlating their local chemistry and microstructure with the extent of local platelet adhesion and activation after blood protein deposition (all measured under otherwise identical experimental conditions) we expect to obtain information about which critical parameters are required for engineering biomaterial interfaces that resist platelet adhesion and activation.

描述（由申请人提供）：筛选血小板与表面梯度的相互作用大多数生物材料在暴露于含蛋白质的环境（如血液）后，在几秒钟内覆盖了蛋白质层。人们普遍认为，生物材料的蛋白质层堆积 - 宿主界面在很大程度上是宿主对生物材料的反应的主要原因。我们建议设计新型的表面梯度，以了解表面参数的不同组合如何介导血蛋白的广告层和随后的血小板相互作用。我们预计拟议的研究中获得的知识将使我们更接近真正的血液相容性生物材料。拟议研究的一般目的是：工程师的新生物材料界面具有选定分子参数的受控表面梯度，并在它们从血液中获取蛋白质层后使用它们来测试血小板粘附和激活。我们建议设计以下空间梯度： - 疏水和亲水性纳米域的梯度， - 表面电荷和偶极子的梯度，以及 - 具有不同链条刚度的亲水性聚合物的表面密度梯度。我们将研究每个梯度参数对：（i）对吸附血浆或血清吸附蛋白的亲和力，（ii）吸附的血液蛋白的分布，动力学和迁移率，以及（iii）血浆的粘附和激活。使用空间控制的分子梯度将使我们能够快速预屏幕效果，即给定的幅度和表面特性对血液蛋白结合以及血小板粘附和激活的结合。筛查阶段将在特定的局部梯度区域进行换位，在该区域中，我们发现血小板粘附到同一表面分子结构的均匀，非梯度版本，以相同的效果进行重新测试。我们方法中的新颖性是在分子梯度方法内置的并行性中。通过使用几个关键表面参数的梯度，并将其局部化学和微观结构与血液蛋白沉积后局部血小板粘附和激活的程度相关联（所有这些都在相同的实验条件下测量），我们希望获得有关抗骨骼粘附和激活的工程生物材料界面所需的关键参数的信息。