Quantification of mechanically-induced growth and remodeling in arteries

It is now unquestioned that cell-mediated vascular growth and remodeling (G&R) plays a key role in many physiological (e.g., normal vascular development) and pathophysiological processes (e.g., hypertension, arteriosclerosis, and the development of aneurysms), as well as the success (or failure) of many clinical interventions (e.g., vein grafts, synthetic vascular grafts, stents, and balloon angioplasty). Evidence from diverse investigations suggests that G&R correlates well with changes in mechanical stresses from their homeostatic values. We present a fundamentally new approach to modeling vascular G&R by considering a constrained mixture model for the adaptation of a cylindrical artery in response to a sustained alteration in flow, pressure, and axial extension. In addition, we perform a parametric study to investigate the relative roles of modeling variables and perform simulations in the setting of tissue-engineered blood vessels. Albeit a first step toward a comprehensive theory that accounts for changes in the 3-D distribution of stress within the arterial wall, including residual stress, and its relation to the mechanisms of mechanotransduction, using a 2-D rule-of-mixtures model for the stress response and first-order kinetics for the production and removal of the three primary load-bearing constituents within the wall, we illustrate capabilities of this model to test competing hypotheses. Findings suggest that biological constraints may result in sub-optimal adaptations, consistent with reported observations. Given the potential of such a model, there is a need for more data on the history of turnover of individual constituents and their individual material properties. Towards this end, we have developed a computer-controlled organ culture and biomechanical testing device designed for small caliber (50--5,000 micron) blood vessels. This device is capable of maintaining precise control of the luminal flow, pulsatile pressure, and axial load (or stretch) and performing intermittent biaxial (pressure-diameter and axial load-length) and functional tests to quantify adaptations in both mechanical behavior and cellular function. Device capabilities are demonstrated by culturing mouse carotid arteries for 4 days.