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

1150397De VitaPelvic底病(PFD)，如尿失禁、大便失禁和盆腔器官脱垂，在美国是一个主要的公共卫生问题，影响到三分之一的成年女性。这些疾病是由盆腔器官、其支持肌肉和结缔组织的结构和机械变化确定的，这些变化主要发生在怀孕、阴道分娩和衰老期间。从直接医疗保健成本、生产力损失和生活质量下降等方面来看，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，这一数字将大幅增加。新的研究预测，受人格障碍影响的成年女性人数将从2010年的2810万人增加到2050年的4380万人。令人震惊的费用负担和预计的PFDs高发病率突出表明，迫切需要在工程和科学方面进行研究，从而制定新的治疗战略。这一职业项目旨在确定支撑子宫和阴道的两种主要韧带的弹性和粘弹性特性：子宫骶部韧带(USL)和主要韧带(CLS)。将对USL和CLS进行严格的机械实验，以完全表征它们作为子宫和阴道支撑性结构的重要作用。随后，力学测试将与同步辐射X射线衍射成像相结合，以前所未有的细节揭示USLs和CLS的胶原蛋白微结构。实验结果将被用来开发基于结构的可靠的超低层和超低层本构模型，并评估它们的预测能力。这些模型将在包含拟线性粘弹性和修正的叠加原理的非线性积分表示理论中推导出来，并且有可能成功地捕捉到超大规模集成电路和超大规模集成电路的机械响应中预期的非线性。该项目将通过提供有关USL和CLS的结构和机械特性的新知识，潜在地改变女性PFDs的外科重建方法和术后康复方案。目前，USLS和CLS要么以特殊方式进行调整，要么使用合成胶带替代，以增强子宫和阴道的悬浮性。这项创新研究将对建立以科学为基础的指导方针和治疗产后功能障碍的具体方案至关重要，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拥有分析技能和实验能力的独特结合，这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学协作访问小组将为PI提供使用同步加速器X射线设施所需的专业知识和培训。通过与沃尔特里德陆军医学中心妇产科的合作，PI将与女性骨盆内科和重建外科的挑战保持同步，并为PFD的护理和管理做出第一手贡献。在这个项目中，研究和教育无缝地结合在一起，以加强学生的课程，并增加未被充分代表的群体在科学和工程领域的参与。该教育计划在弗吉尼亚理工大学和该地区的社区之间建立了新的合作伙伴关系，增加了该协会的总部机构在该州社会和教育倡议中的领导作用。本科生和研究生将参与该项目的拟议研究和教育部分。将开发一门关于生物系统非线性力学的新研究生课程，并对一门本科课程进行重大修订，将实验生物力学的实验时间纳入其中。为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参观者，建议以非科学家可以理解的形式准备互动迷你讲座，并辅之以生物力学方面的动手活动。将为残疾高中生提供夏令营和辅导，以帮助他们过渡到大学。将为工程学女教员组织午餐和小组会议，以创造一个相互支持的环境和指导关系。这些研究和教育工作的结果将在网上传播，在同行评议的期刊上发表，并在国家和国际会议上介绍。

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.