PECASE: Advancing Treatment of Pelvic Floor Disorders through Discoveries in Elasticity and Viscoelasticity of Uterosacral and Cardinal Ligaments

1150397盆底疾病（PFDs），如尿失禁、大便失禁和盆腔器官脱垂，是美国影响三分之一成年妇女的主要公共卫生问题。这些疾病是由盆腔器官及其支撑肌肉和结缔组织的结构和机械改变决定的，主要发生在怀孕、阴道分娩和衰老期间。就直接保健费用、生产力损失和生活质量下降而言，PFDs造成的国家成本负担令人震惊。预计到2050年，随着美国老龄化人口的增加，这一数字将急剧上升。新的研究预测，受PFDs影响的成年女性人数将从2010年的2810万增加到2050年的4380万。令人担忧的费用负担和预计的PFDs高发病率强调了工程和科学研究的迫切需要，从而开发新的治疗策略。这个CAREER项目旨在确定支撑子宫和阴道的两大韧带的弹性和粘弹性特性：子宫骶韧带（USLs）和枢机韧带（CLs）。我们将对usl和CLs进行严格的力学实验，以全面表征其作为子宫和阴道支撑结构的重要作用。机械测试将结合同步加速器x射线衍射成像，以前所未有的细节揭示usl和CLs的胶原微观结构。实验结果将用于为usl和CLs开发可靠的基于结构的本构模型，并评估其预测能力。这些模型将在非线性积分表示理论中推导，该理论包含准线性粘弹性和改进的叠加原理，并且有可能成功捕获usl和CLs力学响应中的预期非线性。知识价值。该项目将通过提供关于usl和CLs结构和力学特性的新知识，潜在地改变女性pfd的手术重建方法和术后康复方案。目前，usl和CLs要么是临时调整，要么是用合成胶带代替，以增强子宫和阴道的悬浮。这项创新研究对于建立以科学为基础的pfd治疗指南和具体方案至关重要，最终为数百万患有这些疾病的成年妇女提供更好的护理。PI具有独特的分析技能和实验能力，使她特别有资格进行拟议的研究。阿贡国家实验室的生物物理协作访问小组将为PI提供必要的专业知识和使用同步加速器x射线设备的培训。通过与沃尔特里德陆军医疗中心妇产科的合作，PI将随时了解女性骨盆医学和重建手术方面的挑战，并为pfd的护理和管理做出第一手贡献。更广泛的影响。在这个项目中，研究和教育被无缝地整合在一起，以提高学生的课程，并增加科学和工程领域代表性不足群体的参与。教育项目在弗吉尼亚理工大学和该地区的社区之间建立了新的伙伴关系，增加了PI所在机构在该州社会和教育活动中的领导作用。本科生和研究生将参与该项目拟议的研究和教育部分。将开设一门新的研究生课程——生物系统的非线性力学，并对本科课程进行重大修订，以包括实验生物力学的实验时间。互动式迷你讲座辅以生物力学的动手活动，以非科学家可以理解的形式准备，旨在丰富布莱克斯堡中学的科学课程，并吸引西弗吉尼亚州科学博物馆的游客。夏令营和指导将提供给有残疾的高中生，以促进他们向大学的过渡。将为工程专业的女教师组织午餐和小组会议，以创造一个支持性的环境和指导关系。这些研究和教育工作的结果将在网上传播，发表在同行评议的期刊上，并在国家和国际会议上发表。

1150397De VitaPelvic floor disorders (PFDs) such as urinary incontinence, fecal incontinence, and pelvic organ prolapse represent a major public health concern in the United States affecting one third of adult women. These disorders are determined by structural and mechanical alterations of the pelvic organs, their supporting muscles and connective tissues that occur mainly during pregnancy, vaginal delivery, and aging. The national cost burden imposed by PFDs is alarming in terms of direct health care costs, lost productivity, and decreased quality of life. It is projected to increase dramatically by 2050 with the increase in the aging population in the United States. New research forecasts that the number of adult women affected by PFDs will increase from to 28.1 million in 2010 to 43.8 million in 2050. The alarming cost burden and projected high incidence of PFDs emphasize the critical need for research in engineering and science that leads to the development of new treatment strategies. This CAREER project aims at determining the elastic and viscoelastic properties of two major ligaments supporting the uterus and vagina: the uterosacral ligaments (USLs) and cardinal ligaments (CLs). Rigorous mechanical experiments will be performed on USLs and CLs to completely characterize their important role as supportive structures of the uterus and vagina. Mechanical testing will be then coupled with synchrotron X-ray diffraction imaging in order to reveal the collagenous micro-structure of USLs and CLs with unprecedented details. The results of the experiments will be used to develop reliable structurally-based constitutive models for USLs and CLs and assess their predictive capabilities. These models will be derived within a nonlinear integral representation theory, which encompasses the quasi-linear viscoelasticity and the modified superposition principle, and has the potential to successfully capture expected nonlinearities in the mechanical response of the USLs and CLs.Intellectual Merit. This project will potentially transform surgical reconstruction methods and post-operative rehabilitation protocols for female PFDs by offering new knowledge about the structural and mechanical properties of USLs and CLs. Currently, the USLs and CLs are either adjusted in ad-hoc manner or replaced using synthetic tapes for enhancing the suspension of the uterus and vagina. This innovative research will be crucial in establishing science-based guidelines and specific protocols for the treatment of PFDs ultimately providing better care for millions of adult women afflicted by these disorders. The PI has a unique blend of analytical skills and experimental prowess that makes her especially qualified to conduct the proposed research. The Biophysics Collaborative Access Team at the Argonne National Laboratory will provide the PI with the necessary expertise and training to use the synchrotron X-ray facilities. Through the collaboration with the Department of Obstetrics and Gynecology at the Walter Reed Army Medical Center, the PI will keep herself abreast of the challenges in female pelvic medicine and reconstructive surgery and contribute firsthand to the care and management of PFDs.Broader Impact. In this project, research and education are seamlessly integrated to enhance the students' curriculum and increase the participation of underrepresented groups in science and engineering. The education program creates new partnerships between Virginia Tech and the community in the region, increasing the leadership role of the PI's home institution in the state's societal and educational initiatives. Undergraduate and graduate students will participate in the proposed research and education components of the project. A new graduate course on nonlinear mechanics of biological systems will be developed and an undergraduate course will be significantly revised to include laboratory hours in experimental biomechanics. Interactive mini-lectures complemented with hands-on activities in biomechanics, prepared in formats understandable by non-scientists, are proposed to enrich the science curriculum at the Blacksburg Middle School and engage the visitors of the Science Museum of Western Virginia. Summer camps and mentorship will be offered to high school students with disabilities in order to facilitate their transition to college. Lunch and group meetings for women faculty in engineering will be organized to create a supportive environment and mentoring relationships. The findings of these research and education efforts will be disseminated on the web, published in peer-reviewed journals, and presented at national and international conferences.