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

这项教师早期职业发展（Career）资助将支持研究缺陷和损伤如何改变软组织的局部生物力学环境，以促进诸如失败或破裂之类的灾难性事件。当组织承受的载荷超过组织的强度时，就会发生机械故障。软组织破裂会对人体健康造成毁灭性的后果，这取决于软组织在体内的位置。然而，由于使用传统的实验方法无法实现所需的局部生物力学特征，因此预测促进软组织衰竭的位置和条件可能具有挑战性。为了解决软组织生物力学中这一长期存在的挑战，这项工作将利用开创性的基于光学的机械测试和成像方法，试图通过实验表征小鼠动脉组织缺陷的局部环境。实验结果将用于主动脉破裂的计算模型。本研究的成果和技术进步将适用于多种生理系统软组织的失效分析。这项工作将与一个教育平台整合在一起，该平台专注于开放科学，可访问基于光学的机械测试技术，并为学生提供参与交互式STEAM教育活动的机会。本研究的目的是更好地了解局部主动脉壁缺陷的生物力学后果，并利用创新的力学生物学、微观结构和力学测试方法来表征导致主动脉破裂的因素。为了实现这一目标，空间生物学测量将被映射到全场生物力学测量中，以发展组织缺陷内部和周围的局部结构功能关系。具体的研究目标包括利用1)创伤性主动脉损伤的离体模型和2)胸腔主动脉病变的体内模型对局部主动脉壁缺陷和疲劳引起的衰竭传播进行全面的生物力学评估，这将为3)基于颗粒的软组织衰竭计算模型提供信息。此外，教育推广计划将为来自不同背景，年龄和经验水平的学生（K-6，大学和监禁的成年人）提供机会，参与STEAM活动，包括新的光学和物理课程，以及与光学和镜子，材料结构和功能以及心血管健康相关的实践演示。总之，这一联合研究和教育计划将促进该领域对局部软组织破裂机制的理解，同时教授学生心血管健康和机械生物学的重要性。生物、物理和工程的综合暴露将促进对跨学科STEAM职业的兴趣，并提高生物医学劳动力的保留率和多样性。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.