In-silico Vascular Growth and Remodeling Insights From Coupling Biology and Mechanics

Vascular growth and remodeling is a complex multi-step process, during which the vasculature attempts to maintain homeostasis in the blood vascular system by changing its micro and macrostructure in response to alterations in its bio-chemo-mechanical environment. A better understanding of this process is imperative to identifying better treatments for cardiovascular diseases, developing tissue-engineered constructs, and advancing our knowledge of tumor angiogenesis. However, despite being the focus of research for the past three decades and the wealth of information at our hands, a holistic theory, that can connect the microscale alterations in the cellular behavior to the macroscale changes in the geometry and composition of the blood vessels, seems yet elusive. Computational models have been a valuable tool in this regard. But, the utility of these models has remained limited, as the majority of existing models either focus on the biology or the mechanics and, naturally, cannot capture the emergent aspects of these complex processes. This work presents a novel Agent Based

• Finite Element Analysis modeling framework that allows us to study vascular adaptation in response to changes in the mechanobiological stimuli. We studied the arterial wall under normal conditions and during perturbations in biochemomechanical stimuli and proved the stability of the model. In the last step, we utilized the model to study the effects of various loading modes (uniaxial, biaxial, and equibiaxial) and serum concentration on the formation and alignment of collagen fibers in Tissue Engineered Vascular Grafts. We showed that biaxial loading is crucial for the physiological alignment of collagen fibers and serum concentration does not affect the alignment of the fibers but can affect the growth and remodeling speed.