ALL blood-wetted devices, without exaggeration, are susceptible to unintended thrombosis and bleeding ? with dire consequences. In spite of decades of clinical experience, basic research, and computational fluid dynamics modeling, it is still virtually impossible to avoid deleterious hematological effects without experimental trail-and-error. In fact, in recent years, the incidence of thromboembolic and hemorrhagic adverse events in ventricular assist devices (VADs) has increased, not decreased. The unfortunate consequence is an unacceptable rate of debilitating adverse events such as stroke and hemorrhage. This has motivated the PI and colleagues over the past two decades to develop an accurate, computational model to simulate the process of thrombus deposition on artificial surfaces. The computer simulation is unique in its ability to account for physical and biological phenomena on multiple-scales, including the trafficking of red blood cells and platelets in small spaces, synthesis and transport of chemical agonists, and several pathways for positive- and negative feedback of platelet adhesion to artificial surfaces. The current model has demonstrated excellent agreement with experimental observations in microfluidic channels and the HeartMate-2 blood pump. The objective of this competitive renewal is to continue improvement of the versatility of this model, and to demonstrate its translation to full-scale blood-wetted devices. The two Specific Aims of this study are: SA1, to improve the fidelity of the model by adding important mechanisms of platelet disaggregation, thrombolysis, and von Willebrand mediated platelet adhesion; and SA2, to demonstrate and further validate the performance of the model with contemporary blood pumps and oxygenators in clinical use. Successful completion of these aims will yield a comprehensive computational model for thrombosis in blood-wetted devices, which we believe will contribute to the inevitable paradigm shift in developing these devices: replacing trial-and-error with prescriptive quantitative methods. Combined with computer optimization, the use of this model will greatly accelerate development of safe and effective new devices, and will reduce the occurrence of adverse complications. We also envision that the models will also be used forensically to analyze thrombosis-related adverse events, and help guide management of anticoagulation therapy.

Public Health Relevance

Cardiovascular devices that are implanted today carry a risk of un-intended blood clotting, which may cause serious injury including stroke and bleeding. The purpose of this project is to create a computer simulation program that will predict when this might occur, and thereby help doctors adjust dosage of blood-thinners, and guide developers of these devices to produce more safe and effective devices.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL089456-09
Application #
9925233
Study Section
Bioengineering, Technology and Surgical Sciences Study Section (BTSS)
Program Officer
Qasba, Pankaj
Project Start
2018-05-01
Project End
2021-03-31
Budget Start
2020-04-01
Budget End
2021-03-31
Support Year
9
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Cornell University
Department
Engineering (All Types)
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Olia, Salim E; Wearden, Peter D; Maul, Timothy M et al. (2018) Preclinical performance of a pediatric mechanical circulatory support device: The PediaFlow ventricular assist device. J Thorac Cardiovasc Surg 156:1643-1651.e7
Blue Martin, A; Wu, Wei-Tao; Kameneva, Marina V et al. (2017) Development of a High-Throughput Magnetic Separation Device for Malaria-Infected Erythrocytes. Ann Biomed Eng 45:2888-2898
Wu, Wei-Tao; Jamiolkowski, Megan A; Wagner, William R et al. (2017) Multi-Constituent Simulation of Thrombus Deposition. Sci Rep 7:42720
Wu, Wei-Tao; Yang, Fang; Wu, Jingchun et al. (2016) High fidelity computational simulation of thrombus formation in Thoratec HeartMate II continuous flow ventricular assist device. Sci Rep 6:38025
Jamiolkowski, Megan A; Pedersen, Drake D; Wu, Wei-Tao et al. (2016) Visualization and analysis of biomaterial-centered thrombus formation within a defined crevice under flow. Biomaterials 96:72-83
Olia, Salim E; Maul, Timothy M; Antaki, James F et al. (2016) Mechanical blood trauma in assisted circulation: sublethal RBC damage preceding hemolysis. Int J Artif Organs 39:150-9
Wu, Wei-Tao; Martin, Andrea Blue; Gandini, Alberto et al. (2016) Design of microfluidic channels for magnetic separation of malaria-infected red blood cells. Microfluid Nanofluidics 20:
Wu, Wei-Tao; Yang, Fang; Antaki, James F et al. (2015) Study of blood flow in several benchmark micro-channels using a two-fluid approach. Int J Eng Sci 95:49-59
Yang, Fang; Kormos, Robert L; Antaki, James F (2015) High-speed visualization of disturbed pathlines in axial flow ventricular assist device under pulsatile conditions. J Thorac Cardiovasc Surg 150:938-44
Jamiolkowski, Megan A; Woolley, Joshua R; Kameneva, Marina V et al. (2015) Real time visualization and characterization of platelet deposition under flow onto clinically relevant opaque surfaces. J Biomed Mater Res A 103:1303-11

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