CAREER: Understanding the Biomechanical Consequences of Local Tissue Defects on Aortic Rupture

Washington University, Saint Louis MO

Investigators

Abstract

This Faculty Early Career Development (CAREER) grant will support research that investigates how defects and damage alter the local biomechanical environment of soft tissues to promote catastrophic events such as failure or rupture. Mechanical failure occurs when the loads experienced by a tissue exceed the tissue’s strength. Depending on the location in the body, soft tissue rupture can have devastating consequences for human health. However, predicting the location and conditions that promote soft tissue failure can be challenging since the required local biomechanical characterizations cannot be realized using traditional experimental approaches. To address this longstanding challenge in soft tissue biomechanics, this work will leverage pioneering optics-based mechanical testing and imaging approaches, to attempt to experimentally characterize the local environment of tissue defects in mouse arteries. Experimental findings will be used to inform a computational model of aortic rupture. Outcomes and technological advances stemming from this research will be applicable to failure analysis in soft tissues from multiple physiological systems. This work will be integrated with an educational platform focused on open-science, accessibility to optics-based mechanical testing technologies, and opportunities for students to participate in interactive STEAM educational activities. The goal of this research is to better understand the biomechanical consequence of localized aortic wall defects and characterize the factors that contribute to aortic rupture using innovative mechanobiological, microstructural, and mechanical testing approaches. To accomplish this goal, spatial biological measurements will be mapped onto full-field biomechanical measurements to develop local structure-function relationships in and around tissue defects. Specific research objectives include a comprehensive biomechanical assessment of local aortic wall defects and fatigue-induced failure propagation using 1) ex vivo model of trauma-induced aortic damage and 2) in vivo model of thoracic aortopathy that will inform 3) particle-based computational model of soft tissue failure. Additionally, an educational outreach program will provide opportunities for students from diverse backgrounds, ages, and levels of experience (K-6, university, and incarcerated adults) to participate in STEAM activities including new optics- and physics-based coursework and hands-on demonstrations related to optics and mirrors, material structure and function, and cardiovascular health. Together, this combined research and educational plan will advance the field’s understanding of local soft tissue rupture mechanisms while teaching students about the importance of cardiovascular health and mechanobiology. The integrated exposure to biology, physics, and engineering will promote interest in interdisciplinary STEAM careers and enhance retention and diversity in the biomedical workforce. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.