A fully coupled framework for in silico investigation of in-stent restenosis.

Finite element analysis (FEA) can be implemented along with Agent-based model (ABM) to investigate the biomechanical and mechanobiological mechanisms of pathophysiological processes. However, traditional ABM-FEA approaches are often partially coupled and lack the feedback responses from biological analysis. To overcome this problem, a fully coupled ABM-FEA framework is developed in this paper by linking the macro-scale and cell-scale modules bi-directionally. Numerical studies of the in-stent restenosis process are conducted using the proposed approach and comparisons are made between the two types of frameworks. A reduction in lumen loss rate, which is possibly caused by the time-varying stresses, is observed in the fully coupled simulations. The re-endothelialisation process is also simulated under different frameworks and the simulation results show strong inhibition of endothelial cells to vascular restenosis. The proposed method is proved to be effective to explain the biomechanical-mechanobiological coupling characteristics of the restenosis problem and can be utilized for stent design and optimization.