Coupled Finite Element–Agent-Based Models for the Simulation of Vascular Growth and Remodeling

Abstract Agent-based models (ABMs) are increasingly used to simulate biological systems, for example, to model the growth of cells in various tissues. Individual agents are defined such that they obey simple rules governed by their internal state and external environment. An ABM can then combine the individual behavior of numerous agents, and the interactions between agents, to predict the collective behavior of the agents in a model system, such as a tissue or organ. From this, complex behavior can be simulated and stochastic methods employed to predict emergent behavior. In this chapter, an ABM coupled with a finite element (FE) model is presented and used to predict in-stent restenosis in an artery wall after stent implantation. The ABM features two cell types: vascular smooth muscle cells and endothelial cells whose behaviors are interdependent. The rule set for cell–cell interactions is presented, including derivation from experimental and clinical data in the literature, along with details of the implementation methods. Cell behavior is principally governed by the mechanical environment in the model whereby a nonlinear FE model of stent deployment is coupled to the domain of the ABM. Challenges with model calibration and validation are discussed, along with potential future applications of this modeling approach to areas such as vascular tissue engineering and remodeling.