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：
10033067
负责人：
CHRISTOPHER A SIEDLECKI
金额：
$ 65.11万
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/10033067
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.

项目摘要/摘要血栓形成和感染仍然是晚期血液发展和实施的重大障碍联系医疗设备。该应用的目的是创建和测试新颖的生物材料结合化学和表面纹理方法，以提高血流相容性。我们将发展小说，一氧化氮（NO） - 释放聚合物（PU）材料，地形范围从10秒到10 100纳米的纳米，并将在兔子体模型和高级台式测试中进行测试。这工作的中心假设指出血小板粘附/激活和细菌粘附受表面化学和表面物理特性。生物材料表面具有地形结合修饰，聚合物化学和主动分子释放，使血小板具有抗性根治性的粘附将提高这些材料在减少血小板方面的效率粘附/激活和细菌粘附/生物膜形成超出预期从体外和体内条件下的单个修饰策略中。为了检验这一假设，我们提出了3个特定目的，涉及在兔模型中测试导管的时期 7和28天。这些导管将基于我们发表的研究，显示了台式的成功通过实施亚微米纹理而无需释放来减少血小板和细菌的粘附。在AIM 2中，我们将开发更高级的纹理协议，其中包含从10 mint的功能尺寸简单地完成100纳米的纳米，也将不包含任何释放。我们还将开发一本小说基于多磷酸化学的材料在台式测试中表现出了有希望的结果，但需要改进，适合纹理，无需释放导管构型。最后，我们将执行这些材料的基础科学研究是为了确定使材料可能的特征在导管模型中取得成功，并告知生物材料社区有关的过程总体上，血小板粘附，生物膜形成和血液凝结。成功完成应用将提供一种新的方法来改善当前生物材料的生物相容性，改善患者护理和节省成本。