The investigators proposes to study platelet responses to high shear stresses via coordinated, mechanistic studies involving in vitro bioengineering experiments combined with biocomputational simulations. One of the main innovations of the project is that pathophysiologically relevant shear exposure times and magnitudes will be studied, in contrast to the vast majority of prior platelet function studies that employed time exposures on the order of seconds to minutes. A microfabricated experimental platform is to be developed to investigate blood damage in dynamic fluidflowing environments with mechanical stresses of magnitude and duration typical of cardiovascular devices and occlusive arterial disease. Another innovation of this project is the use of computational fluid dynamics (CFD) in conjunction with experiments to jointly provide complete fluid dynamic information for blood damage analysis. This reliance upon CFD to provide such vital information is unique among platelet function studies performed to date.
Biomedical devices are frequently employed to repair or replace various elements of the cardiovascular system. Prosthetic heart valves, vascular grafts, circulatory assist devices, and hemodialysis systems are in wide clinical use, often saving or extending the lives of patients with otherwise hopeless medical conditions. This project will provide a deeper understanding of the interactions of blood flow with the dynamics of blood damage may yield new insights into the mechanisms of blood damage and, thus, enable further progress in the design, evaluation, and improvement of cardiovascular devices as well as provide direction for new preventative clinical therapies. The outcomes of this project will impact FDA (U.S. Food and Drug Administration) submission packages by providing guidelines and validated models of blood damage to better evaluate the efficacy and performance of future devices. In addition, the project has a substantive educational impact through the involvement of undergraduate and graduate students with this research. The biomechanics of blood damage will be taught in bioengineering classroom settings, and graduate students will experience cross-disciplinary training via laboratory visits between the computational and experimental facilities involved in this project.
