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

当生物材料与血液等生物流体接触时，蛋白质吸附迅速发生，并影响随后与细胞的相互作用，包括血小板、白细胞(白血球)和微生物。对于导管、支架、血管移植物、氧合器和血液透析器等医疗设备，这些反应可能导致血液凝结(血栓形成)、炎症或感染，最终导致设备故障。尽管取得了进展并不断努力，但要使大多数血液接触设备发挥作用，仍然需要抗凝剂和抗血小板药物，使用这些药物可能会导致严重的并发症。为了改善生物材料，可以应用表面改性来改变材料的物理、化学或生物特性。控制纳米级性质的物理修饰和生物功能化的组合可以影响蛋白质配体的呈现，从而控制细胞反应并减少不良反应。这项研究计划的长期目标是使用先进的表面改性方法来改进血液接触设备，以增强对蛋白质和细胞与多功能材料相互作用的了解。为了实现这一目标，我们在未来5年的短期目标是：(1)设计和表征微纳结构材料，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相结合，创建多功能材料，并确定白细胞和血小板的反应；以及(3)开发并应用先进的蛋白质和细胞分析方法，用于对多功能材料进行系统和动态测试的设备几何形状。该研究计划的成功将对生物材料领域以及其他领域产生重大影响，包括聚合物、表面和界面表征。它将增强对纳米尺度表面特征、蛋白质结构变化和细胞对表面的反应的基础理解，使研究人员能够更好地表征和控制改进的生物材料的相互作用。这些研究成果可以转化为组织工程、膜、生物传感器、微流体和纳米医学等广泛领域的材料开发。这项研究将通过解决由于血栓形成、炎症和感染而影响一系列设备功能的生物材料问题，使加拿大受益。这些并发症的经济负担很高，并导致严重的发病率和死亡率。因此，这项研究的成功具有重大的社会经济优势，包括降低医疗成本和改善健康结果。该计划将培训HQP，使其能够获得最先进的设备和方法，以提高生物医学工程跨学科和新兴领域的技能。

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.