Mechanical and structural contributions of extracellular matrix constituents to vascular mechanics
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Elastic and collagen fibers are the major load-bearing extracellular matrix (ECM) constituents of the vascular wall. Elastic fibers accommodate repeated cycles of extension and recoil that occur during pulsatile blood flow at lower levels of strain, whereas the recruitment of collagen fibers at higher levels of strain leads to nonlinear stiffening that protects blood vessels from overextension. Glycosaminoglycans (GAGs) provide a structural basis for multiple biological functions, such as the organization of ECM and the regulation of cell growth factors. There exists a complex interdependence of ECM compositional, structural, and mechanical properties. The overall goal of the research is to study the biomechanical and structural roles of different ECM constituents in vascular mechanics through coupled mechanical testing, advanced optical imaging, and microstructure-based constitutive modeling. Arteries function differently than veins in the circulatory system, however in several treatment options veins are subjected to sudden elevated arterial pressure. Our study improves the understanding of elastin and collagen fiber contribution to ECM mechanics of different vessel types. Our research demonstrates that ECM fiber distribution, recruitment, and content each play an important role in vascular function, and the important structural and functional differences between arteries and veins that should be taken into account when considering treatment options. While elastin and collagen have received extensive consideration, little is known about the biomechanical roles of GAGs in blood vessels. The mechanics of tissue with low GAG content can be indirectly affected by the interaction of GAGs with collagen fibers, which is one of the primary contributors to arterial mechanics. Our study suggests that that the interaction between GAGs and other ECM constituents plays an important role in the mechanics of the arterial wall, and GAGs should be considered in addition to elastic and collagen fibers when studying arterial function. A structure-based constitutive model was then developed to successfully predict arterial mechanics considering the contribution of GAGs to fiber recruitment. Building upon previous research, ongoing work is presented to study the fundamental yet clinically relevant structural-mechanical behavior of arterial ECM in diabetes using an integrated experimental and modeling approach.