Combinatorial Approaches to Improved Blood-contacting Polymer Biomaterials

项目概要/摘要 血栓形成和感染仍然是发展和实施先进血液系统的重大障碍。 接触医疗器械。本申请的目的是创造和测试新的生物材料， 结合联合收割机化学和表面纹理方法以改善血液相容性。我们将开发新的， 一氧化氮（NO）释放聚合物（PU）材料，其形貌尺度范围从几十微米到几十微米。 100的纳米，并将测试这些在兔子导管模型和先进的台式测试。的 这项工作的中心假设指出， 血小板粘附/活化和细菌粘附受表面化学和 表面物理性质生物材料表面承载着地形的组合 修饰、聚合物化学和活性分子释放， 并且细菌粘附将增加这些材料在减少血小板方面的功效 粘附/活化和细菌粘附/生物膜形成超出预期 在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3个具体的目标，包括在兔子模型中测试导管， 7和28天。这些导管将基于我们已发表的研究，这些研究表明， 通过实施具有NO释放的亚微米纹理化来减少血小板和细菌粘附。在目标2中， 我们将开发更先进的纹理协议，包括特征尺寸从10微米到100微米， 到100纳米的同时，也将纳入NO释放。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 改进以适合于在导管构造中纹理化和NO释放。最后，我们将执行 对这些材料进行基础科学研究，以确定使材料可能 在导管模型中取得成功，并向生物材料界通报 血小板粘附、生物膜形成和一般的血液凝固。成功完成本 本发明的应用将为改善现有生物材料的生物相容性、提高生物相容性和生物相容性提供新的途径。 患者护理和节省成本。

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.