TITLE: ARTERIAL MECHANICS CONSIDERING MULTI-SCALE STRUCTURAL INHOMOGENEITY IN THE EXTRACELLULAR MATRIX.
ABSTRACT: Elastic and collagen fibers are the major extracellular matrix (ECM) constituents of the arterial wall. Elastic fibers in the medial layer form concentric layers of elastic lamellae, together with smooth muscles cells and collagen fibers, organizing into a lamellar unit that is considered as a functional unit of the arterial wall. The ECM fiber networks in the arterial wall are highly inhomogeneous. The objective of this work is to advance the current understanding of multi-scale ECM mechanics and the important role of structural inhomogeneity using a coupled experimental and modeling approach that integrates mechanical characterization, advanced optical imaging, and computational modeling.
Our study revealed the existence of microstructural inhomogeneity in the arterial wall at inter- and intra- lamellar structural levels. At the inter-lamellar level, we showed that there is a transmural variation in the orientation distribution of elastic fibers through the arterial wall. Consideration of such structural inhomogeneity improved the fitting and predicting capability of a structural-based constitutive model in dictating the nonlinear anisotropic mechanical behavior of the arterial wall. Our study on the micromechanics of elastic lamellae showed that structural inhomogeneity is important in maintaining tissue homeostasis. Specifically, the higher lamellar
unfolding in the inner lamellar layers compensates the larger strain experienced at the inner surface of the arterial wall, and plays an important role in maintaining a more evenly distributed stretching/stress in the lamellar layers. While the aforementioned structural inhomogeneities are important for maintaining arterial function and tissue homeostasis, structural inhomogeneity in fiber diameters, density, orientation distribution can also lead to large variations in local fiber stresses as well as in local ECM mechanical properties. At the intra-lamellar level, using a discrete fiber network (DFN) model, we showed that fiber-fiber interactions play an important role in fiber strain and kinematics upon tissue deformation. Finally, by studying the dissection properties of arterial media through peeling tests, we discovered that the propagation process of aortic dissection is governed by an avalanche-like cascade failure of the inhomogenously distributed inter-lamellar collagen fibers. This power-law behavior in the arterial wall provides new understandings of the biomechanics of aortic dissection. This thesis research revealed that there are complex interplays between the structure and mechanics of ECM, which need to be considered in advancing the current understanding of multi-scale ECM mechanics and arterial remodeling in pathological conditions.
COMMITTEE: ADVISOR Professor Katherine Yanhang Zhang, ME/BME/MSE; CHAIR Professor Xin Zhang, ME/ECE/BME/MSE; Professor Bela Suki, BME/MSE; Professor Elise Morgan, ME/MSE/BME; Professor Chiara Bellini, Bioengineering, Northeastern University