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

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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.