Combinatorial Approaches to Improved Blood-contacting Polymer Biomaterials

改进血液接触聚合物生物材料的组合方法

基本信息

批准号：
10237331
负责人：
CHRISTOPHER A SIEDLECKI
金额：
$ 65.16万
依托单位：
PENNSYLVANIA STATE UNIV HERSHEY MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-15 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10237331
关键词：
Address Adhesions Adsorption Affect Animal Model Animal Testing Anti-Bacterial Agents Architecture Area Bacteria Bacterial Adhesion Basic Science Biocompatible Materials Biological Blood Blood Platelets Blood coagulation Catheters Characteristics Chemical Structure Chemicals Chemistry Coagulation Process Communities Conscious Cost Savings Data Development Devices Dimensions Film Generations Goals Heart-Assist Devices Implant In Vitro Infection Materials Testing Medical Device Methods Microbial Biofilms Modeling Modification N-acetylpenicillamine Nitric Oxide Oryctolagus cuniculus Patient Care Pattern Plasma Polymer Chemistry Polymers Polyurethanes Process Property Proteins Protocols documentation Publishing Resistance S-nitro-N-acetylpenicillamine Science Series Surface Surface Properties Testing Texture Thinness Thrombosis Time Ursidae Family Work antimicrobial base biomaterial compatibility blood pump chemical function clinical development combinatorial design early phase clinical trial experimental study hemocompatibility improved in vivo mechanical properties microbial nano nanofabrication nanometer nanoscale novel novel strategies physical property polyphosphazene response submicron success

项目摘要

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.

项目概要/摘要血栓形成和感染仍然是先进血液技术开发和实施的重大障碍。该应用的目的是创建和测试新型生物材料。我们将结合化学和表面纹理方法来改善血液相容性。释放一氧化氮 (NO) 的聚合物 (PU) 材料，其形貌范围从 10 微米到数百纳米，并将在兔子导管模型和先进的台式测试中对其进行测试。该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细菌粘附的影响具有地形组合的生物材料表面。修饰、聚合物化学和活性分子释放赋予血小板抵抗力和细菌粘附将增加这些材料减少血小板的功效粘附/激活和细菌粘附/生物膜形成超出预期来自体外和体内条件下的单一修饰策略。为了检验这一假设，我们提出了 3 个具体目标，其中包括在兔子模型中测试导管一段时间这些导管将基于我们已发表的研究，显示在实验室中取得了成功。在目标 2 中，通过实施亚微米纹理化和 NO 释放来减少血小板和细菌粘附。我们将开发更先进的纹理协议，其中包含 10 微米的特征尺寸同时达到 100 纳米，并且还将包含 NO 释放，我们还将开发一种新型。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，但仍需要最后，我们将进行改进以适合导管配置中的纹理和 NO 释放。对这些材料进行基础科学研究，以确定这些材料可能的特性成功建立导管模型，并向生物材料界通报涉及的流程血小板粘附、生物膜形成和血液凝固总体上顺利完成。应用将为提高现有生物材料的生物相容性、改善患者护理并节省成本。