Multiscale modeling of thrombosis by finite element (FE) and dissipative particle dynamics (DPD) in the large arteries

To better understand the mechanisms leading to the formation and growth of mural thrombi on biomateriats, we have developed a comprehensive model of platelet-mediated thrombogenesis including platelet activation, platelet transport in flowing blood, effects of artificial surfaces, kinetics and mechanics of platelet-platelet and platelet surface adhesion. We used a multiscale procedure to couple a mesoscale discrete particle model and a macroscale continuum finite element (FE) model of blood flow. A dissipative particle dynamics (DPD) method treats the blood (i.e., colloidal-composed medium) as a group of meso-scale particles interacting through conservative, dissipative and random forces. The entire blood flow domain is divided into a local domain and a global domain. Blood flow in the local domain is modeled with both DPD and FE method, while blood flow in the global domain is modeled by the FE method only. The boundary conditions for the DPD model at the local-global domain boundary are based on the following two assumptions: a) the number of particles is preserved in the local domain (periodic boundary conditions), and b) at the local-global domain boundary particle velocities are equal to the continuum FE velocities. DPD method for blood plasma and platelets are discretized into Voronoy cells and treated as mesoscopic size particles. The vessel walls are considered rigid. Aggregation and adhesion of activated platelets are modeled by considering attractive forces generated from von Willebrand factor at the blood vessel wall. The values of the effective spring constants characterize the bond stiffness of the aggregation/adhesion interaction. To test this model, we simulated the platelet deposition in a perfusion chamber. By matching the simulation results to the experiments, the effective platelet aggregatiodadhesion spring constants were determined and were found to be within reasonable ranges. We conclude that our new multiscale FE-DPD analysis provides the capability of simulating the time-dependent adhesion of platelets in the large arteries. This model offers a new tool that gives an insight into the process of thrombosis in a wide range of biomaterials and complex blood flows.