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

职业：了解局部组织缺陷对主动脉破裂的生物力学影响

• 批准号: 2340666
• 负责人: Matthew Bersi
• 金额: $ 57.49万
• 依托单位: Washington University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-07-01 至 2029-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2340666&HistoricalAwards=false
• 关键词: CAREER; Understanding; Biomechanical; Consequences; Local

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.

该学院早期职业发展（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，以促进失败或破裂等灾难性事件。当组织经受的载荷超过组织的强度时，发生机械失效。根据在体内的位置，软组织破裂可能对人体健康造成破坏性后果。然而，预测的位置和条件，促进软组织故障可能是具有挑战性的，因为所需的局部生物力学特性不能实现使用传统的实验方法。为了解决软组织生物力学中的这一长期挑战，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，试图通过实验来表征小鼠动脉中组织缺损的局部环境。实验结果将被用来通知主动脉破裂的计算模型。这项研究的成果和技术进步将适用于多个生理系统的软组织失效分析。这项工作将与一个专注于开放科学的教育平台相结合，可访问基于光学的机械测试技术，并为学生提供参与互动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损的生物力学后果，并使用创新的机械生物学，显微结构和机械测试方法表征导致主动脉破裂的因素。为了实现这一目标，空间生物测量将映射到全场生物力学测量，以开发组织缺损内和周围的局部结构-功能关系。具体的研究目标包括使用1）创伤诱导的主动脉损伤的离体模型和2）将告知3）软组织失效的基于颗粒的计算模型的胸部动脉病的体内模型对局部主动脉壁缺损和疲劳诱导的失效传播进行全面的生物力学评估。此外，教育推广计划将为来自不同背景，年龄和经验水平（K-6，大学和被监禁的成年人）的学生提供参与STEAM活动的机会，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，这一结合的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，同时向学生传授心血管健康和机械生物学的重要性。综合接触生物学，物理学和工程学将促进跨学科STEAM职业的兴趣，并提高生物医学劳动力的保留和多样性。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。