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

• 批准号: 10461019
• 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
• 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/10461019
• 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; 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

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。 接触医疗设备。该应用程序的目的是创建和测试新型生物材料 结合化学和表面纹理方法来改善血液相容性。我们将开发新颖、 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。这 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 表面物理性质。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 7天和28天。这些导管将基于我们已发表的研究，该研究表明在实验室中取得了成功 通过实施亚微米纹理并释放 NO，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，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，但仍需要 改进以适合导管结构中的纹理和 NO 释放。最后，我们将进行 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的一般情况。本次活动的顺利完成 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。