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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：
10680549
负责人：
CHRISTOPHER A SIEDLECKI
金额：
$ 64.35万
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/10680549
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 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 Science Series Surface Surface Properties Testing Texture Thinness Thrombosis Time Work antimicrobial biomaterial compatibility blood pump chemical stability clinical development combinatorial design early phase clinical trial experimental study hemocompatibility improved in vivo manufacture mechanical properties medical implant microbial nano nanometer 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.

项目总结/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。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Surfaces modified with small molecules that interfere with nucleotide signaling reduce Staphylococcus epidermidis biofilm and increase the efficacy of ciprofloxacin.

DOI：
10.1016/j.colsurfb.2023.113345
发表时间：
2023-05
期刊：
Colloids and surfaces. B, Biointerfaces
影响因子：
0
作者：
Li-Chong Xu;Alyssa Ochetto;Chen Chen-Chen;Dongxiao Sun;H. Allcock;C. Siedlecki
通讯作者：
Li-Chong Xu;Alyssa Ochetto;Chen Chen-Chen;Dongxiao Sun;H. Allcock;C. Siedlecki

Crosslinkable fluorophenoxy-substituted poly[bis(octafluoropentoxy) phosphazene] biomaterials with improved antimicrobial effect and hemocompatibility.

DOI：
10.1002/jbm.b.35252
发表时间：
2023-08
期刊：
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS
影响因子：
3.4
作者：
Alwine, Shelby;Chen, Chen;Shen, Lihui;Allcock, Harry R.;Siedlecki, Christopher A.;Xu, Li-Chong
通讯作者：
Xu, Li-Chong

In vitro evaluation of blood plasma coagulation responses to four medical-grade polyurethane polymers.

DOI：
10.1177/08853282231191410
发表时间：
2023-08
期刊：
JOURNAL OF BIOMATERIALS APPLICATIONS
影响因子：
2.9
作者：
Nguyen, Lan;Xu, Li-Chong;Yeager, Eric;Weiss, William J.;Siedlecki, Christopher A.
通讯作者：
Siedlecki, Christopher A.

Nucleotide Messenger Signaling of Staphylococci in Responding to Nitric Oxide - Releasing Biomaterials.