Engineered surfaces for the control of protein and cell interactions and improved biomedical materials

用于控制蛋白质和细胞相互作用的工程表面以及改进的生物医学材料

• 批准号: RGPIN-2022-05258
• 负责人: Sask, Kyla
• 金额: $ 1.89万
• 依托单位: McMaster University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=758268
• 关键词: Engineered; surfaces; control; protein; cell

When biomaterials come in contact with biological fluids such as blood, protein adsorption occurs rapidly and influences subsequent interactions with cells, including platelets, leukocytes (white blood cells), and microbes. For medical devices such as catheters, stents, vascular grafts, oxygenators and hemodialyzers, these responses can lead to blood clotting (thrombosis), inflammation or infection, and ultimately failure of the device. Despite progress and ongoing efforts, for most blood contacting devices to function, anticoagulant and antiplatelet drugs are still required, and their use can lead to serious complications. In order to improve biomaterials, surface modifications can be applied to alter the physical, chemical or biological properties of the material. A combination of physical modifications to control nanoscale properties along with biofunctionalization can influence protein ligand presentation, allowing control of cell response and reduction of adverse reactions. The long-term goal of this research program is to achieve an enhanced understanding of protein and cell interactions with multifunctional materials using advanced surface modification methods for improved blood contacting devices. To pursue this goal, in the next 5 years, our short-term objectives are: (1) Design and characterize micro- and nano-structured materials to control protein structural changes and identify mechanisms leading to leukocyte and platelet response; (2) Create multifunctional materials by combining physical surface modifications with bioactive functionalizations and determine leukocyte and platelet response; and (3) Develop and apply advanced protein and cell analysis methods to device geometries for systematic and dynamic testing of multifunctional materials. The success of the proposed research program will significantly impact the biomaterials field, and others including polymers, surfaces and interfacial characterization. It will provide an enhanced fundamental understanding of nanoscale surface features, protein structural changes and cellular responses with surfaces, allowing researchers to better characterize and control interactions for improved biomaterials. The research findings can be translated to material development in a breadth of areas including tissue engineering, membranes, biosensors, microfluidics and nanomedicine. This research will benefit Canada by addressing problems with biomaterials that impact the functioning of a range of devices due to thrombosis, inflammation and infection. The financial burden of these complications is high along with the significant morbidity and mortality that results. The success of this research therefore has significant socio-economic advantages including decreased healthcare costs and improved health outcomes. This program will train HQP with access to state-of-the-art equipment and methods to enhance skills in interdisciplinary and emerging areas of biomedical engineering.

当生物材料与血液等生物液接触时，蛋白质吸附会迅速发生，并影响随后与细胞的相互作用，包括血小板，白细胞（白细胞）和微生物。对于医疗器械，例如导管，支架，血管移植物，氧合和血液聚会器，这些反应会导致血液凝结（血栓形成），炎症或感染以及最终导致设备失败。尽管进步和持续的努力，对于大多数血液接触设备的功能，仍需要抗凝药和抗血小板药物，并且它们的使用可能导致严重的并发症。为了改善生物材料，可以使用表面修饰来改变材料的物理，化学或生物学特性。对控制纳米级特性以及生物功能化的物理修饰的结合可以影响蛋白质配体的表现，从而可以控制细胞反应和减少不良反应。 该研究计划的长期目标是通过使用先进的表面修饰方法来增强对蛋白质和细胞相互作用的了解，以改善血液接触装置。为了实现这一目标，在接下来的5年中，我们的短期目标是：（1）设计和表征微型和纳米结构的材料，以控制蛋白质结构变化并确定导致白细胞和血小板反应的机制； （2）通过将物理表面修饰与生物活性功能化结合并确定白细胞和血小板反应来创建多功能材料； （3）将高级蛋白质和细胞分析方法开发到设备几何形状，以进行多功能材料的系统和动态测试。拟议的研究计划的成功将显着影响生物材料领域，以及其他包括聚合物，表面和界面表征。它将提供对纳米级表面特征，蛋白质结构变化以及与表面的细胞反应的增强基本了解，从而使研究人员能够更好地表征和控制改善生物材料的相互作用。研究发现可以转化为在组织工程，膜，生物传感器，微流体和纳米医学等地区的广度上的材料发展。这项研究将通过解决因血栓形成，炎症和感染而影响一系列设备功能的生物材料问题，从而使加拿大受益。这些并发症的财务负担很高，以及导致的大量发病率和死亡率。因此，这项研究的成功具有显着的社会经济优势，包括降低医疗保健成本和改善健康成果。该计划将培训HQP，以获取最先进的设备和方法，以增强生物医学工程跨学科和新兴领域的技能。