Structural modeling of ascending thoracic aortic wall tissue indicates locally elevated biomechanical stresses in regions of collagen fiber disruption

Biomechanical behavior of the ascending thoracic aortic (ATA) wall tissue is primarily governed by the fibrous components of the extracellular matrix (ECM). Microstructural features of the ECM fiber network can give rise to... [ view full abstract ]

Biomechanical behavior of the ascending thoracic aortic (ATA) wall tissue is primarily governed by the fibrous components of the extracellular matrix (ECM). Microstructural features of the ECM fiber network can give rise to regions of focal mechanical stress that in turn may influence structural and functional remodeling of the ECM through mechanosensitive pathways in the vascular smooth muscle cells. To quantify such local heterogeneities of the wall stress, we developed a micro-structural finite element model of the lamellar unit of the ATA media. Our computational model includes multiphoton imaging-derived collagen fiber network explicitly embedded within the non-fibrous matrix and surrounded by two elastic lamellae. A custom nonlinear finite element code was utilized to simulate the biomechanical response of the model. Free parameters of our model were collagen fiber recruitment stretch and elastic moduli of collagen and elastic fibers. These parameters were estimated by regressing model mechanical response against experimental uniaxial stress-strain data, and were found to be in the range reported in the literature. The model revealed that the tissue stress was homogeneous at lower stretch level, but became highly heterogeneous after collagen fiber recruitment at higher stretch. We found a negative correlation between local fiber density and average matrix stress. Interestingly, fiber disruptions, commonly observed in the aortic media of ATA aneurysmal patients with bicuspid aortic valve, gave rise to very high stress concentrations (almost twice the average matrix stress) in the surrounding ECM. These stress hotspots may mediate structural remodeling of the ECM potentially altering tissue mechanical properties.