Combinatorial Approaches to Improved Blood-contacting Polymer Biomaterials

项目摘要/摘要 血栓形成和感染仍然是开发和实施先进血液系统的重要障碍。 接触医疗设备。该应用程序的目标是创建和测试新的生物材料， 结合化学和表面质地处理方法来改善血液相容性。我们将开发小说， 释放一氧化氮的聚合物(PU)材料，其形貌从10‘S微米到 S的纳米技术，并将在兔导管模型和先进的台式测试中测试这些设备。这个 这项工作的中心假设是 血小板黏附/活化和细菌黏附受到表面化学物质和细菌黏附的影响。 表面物理特性。具有组合地形的生物材料表面 具有抗血小板作用的修饰、聚合物化学和活性分子释放 细菌黏附将增加这些材料降低血小板的效果。 黏附/活化和细菌黏附/生物膜的形成超出预期 从体外和体内条件下的单一修饰策略。 为了验证这一假设，我们提出了三个具体目标，包括在兔模型中测试导尿管的周期 7天和28天。这些导尿管将基于我们发表的研究，显示台式电脑在 通过实施无释放的亚微米质地来减少血小板和细菌的粘连。在目标2中， 我们将开发更先进的纹理协议，包含从10微米S到微米的特征大小 到100‘S的纳米同步，还将并入无释药。我们还将开发一部小说 基于聚磷腈化学的材料，在台式测试中显示出有希望的结果，但需要 改进以适用于质地和导管配置中的无释放。最后，我们将开展 对这些材料进行基础科学研究，以确定使这些材料有可能 成功建立导管模型，并向生物材料社区通报涉及的过程 一般情况下，血小板黏附、生物膜形成和凝血。成功地完成这项工作 应用将为改善现有生物材料的生物相容性提供一种新的途径， 护理病人并节省成本。

Project Summary/Abstract Thrombosis and infection remain significant barriers to development and implementation of advanced blood- contacting medical devices. The objective of this application is to create and test novel biomaterials that combine chemical and surface texturing approaches to improve hemocompatibility. We will develop novel, Nitric Oxide (NO)-releasing polymer (PU) materials with topographies ranging in scale from 10’s of microns to 100’s of nanometers and will test these in a rabbit-catheter model and in advanced benchtop testing. The Central Hypothesis of the work states that Platelet adhesion/activation and bacterial adhesion are influenced by both surface chemical and surface physical properties. Biomaterial surfaces bearing a combination of topographic modification, polymer chemistry and active molecule release that impart resistance to platelet and bacterial adhesion will increase the efficacy of these materials in reducing platelet adhesion/activation and bacterial adhesion/biofilm formation beyond what would be expected from a single modification strategy under both in vitro and in vivo conditions. To test this hypothesis, we propose 3 specific aims that involve testing catheters in a rabbit model for periods of 7 and 28 days. These catheters will be based on our published studies showing benchtop success in reducing platelet and bacterial adhesion by implementation of sub-micron texturing with NO release. In Aim 2, we will develop more advanced texturing protocols that incorporate feature sizes ranging from 10’s of microns to 100’s of nanometers simultaneously, and will also incorporate NO release. We will also develop a novel material based on polyphosphazene chemistry that has shown promising results in benchtop testing but needs improvement to be suitable for texturing and NO release in a catheter configuration. Finally, we will carry out basic science studies on these materials in order to identify characteristics that make the materials likely to succeed in a catheter model as well as to inform the Biomaterials Community about processes involved in platelet adhesion, biofilm formation and blood coagulation in general. The successful completion of this application will provide a novel approach to improve the biocompatibility of current biomaterials, improve patient care and incur cost savings.