Hybrid discrete-continuum multiscale model of tissue growth and remodeling.

Tissue growth and remodeling (G&R) is often central to disease etiology and progression, so understanding G&R is essential for understanding disease and developing effective therapies. While the state-of-the-art in this regard is animal and cellular models, recent advances in computational tools offer another avenue to investigate G&R. A major challenge for computational models is bridging from the cellular scale (at which changes are actually occurring) to the macroscopic, geometric-scale (at which physiological consequences arise). Thus, many computational models simplify one scale or another in the name of computational tractability. In this work, we develop a discrete-continuum modeling scheme for analyzing G&R, in which we apply changes directly to the discrete cell and extracellular matrix (ECM) architecture and pass those changes up to a finite-element macroscale geometry. We demonstrate the use of the model in three case-study scenarios: the media of a thick-walled artery, and the media and adventitia of a thick-walled artery, and chronic dissection of an arterial wall. We analyze each case in terms of the new and insightful data that can be gathered from this technique, and we compare our results from this model to several others. STATEMENT OF SIGNIFICANCE: This work is significant in that it provides a framework for combining discrete, microstructural- and cellular-scale models to the growth and remodeling of large tissue structures (such as the aorta). It is a significant advance in that it couples the microscopic remodeling with an existing macroscopic finite element model, making it relatively easy to use for a wide range of conceptual models. It has the potential to improve understanding of many growth and remodeling processes, such as organ formation during development and aneurysm formation, growth, and rupture.