Damage-accumulation failure models are broadly used to examine tissue property changes caused by mechanical loading. However, damage accumulation models are purely phenomenological. The underlying justification in using this type of model is often that damage occurs to the extracellular fibers and/or cells which changes the fundamental mechanical behavior of the system. In this work, we seek to align damage accumulation models with microstructural models to predict alterations in the mechanical behavior of biological materials that arise from structural heterogeneity associated with nonuniform remodeling of tissues. Further, we seek to extend this multiscale model toward assessing catastrophic failure events such as cerebral aneurysm rupture. First, we demonstrate that a model made up of linear elastin and actin and nonlinear collagen fibers can replicate bot the pre-failure and failure tissue-scale mechanics of uniaxially-stretched cerebral aneurysms. Next, we investigate how mechanical heterogeneities, like those observed in cerebral aneurysms, influence fiber and tissue failure. Notably, we find that failure occurs and the interface between regions of high and low material stiffness, suggesting that spatial mechanical heterogeneity influences aneurysm failure behavior. This model system is a step toward linking structural changes in growth and remodeling to failure properties.
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