Mechanical and structural features of the extracellular matrix profoundly affect arterial physiology and pathophysiology. The growth and remodeling (G&R) framework is widely used to describe production, degradation, and reorganization of the matrix proteins that affect arterial homeostasis, but most modeling efforts are focused on describing the acute events, not the long-term remodeling due to aging. We have performed planar biaxial mechanical testing, constitutive modeling, and histological analysis of the intramural structure in >500 human femoropopliteal arteries (FPA) 12 to 99 years old. These data were used to develop a constrained-mixture framework that accounts for the production and removal of arterial load-bearing constituents such as the elastin, collagen, smooth muscle cells, and the ground substance, and recognizes that each of these constituents has a different natural stress-free configuration that evolves with age. Kinematics of G&R deformations due to aging were described at the constituent and tissue levels, and the production and degradation functions for collagen and smooth muscle cells were simplified, given their turnover rates. Linear strain energy functions were used to describe the mechanical behavior of elastin and ground substance, and the exponential Fung-type strain energy functions were utilized to model collagen and smooth muscle cells by accounting for the stiffening of the collagen with age. The proposed framework was able to describe non-linear direction-dependent stiffening of human FPAs due to aging, and allowed to determine arterial residual and physiologic stress-stretch states across the entire lifespan. These data may inform future studies of FPA physiology and pathophysiology, and help design arterial repair devices to improve clinical outcomes of lower extremity interventions and reconstructions.

A Microstructurally-Motivated Growth and Remodeling Framework to Describe Aging of Human Femoropopliteal Arteries

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