LEAP-HI: Coordinated Advances in Reproductive Engineering for Health Research (CARE4HeR)

这个领先的美国繁荣、健康和基础设施工程(LEAP-HI)健康生殖工程协调进展(CARE4HeR)项目的总体目标是通过整合实验、理论和计算力学中的新颖和变革性方法来解决与怀孕和分娩相关的令人震惊的医疗挑战。怀孕和分娩可能对许多妇女、儿童和家庭的健康、健康和生活质量产生悲剧性和破坏性的影响。美国的孕产妇死亡率正在上升，而其他发达国家的与怀孕有关的死亡人数却在下降。早产非常普遍：在美国，每年有50万名婴儿早产。在美国，复杂的阴道分娩占每年分娩总数的16%，是盆底疾病发展的主要风险因素。这些疾病影响了25%的女性，不仅导致身体上的痛苦，还会导致社交孤立、抑郁、焦虑和性功能障碍。存在很大的种族和族裔差异，非裔美国人的产妇死亡率和早产率较高。尽管几个因素无疑起了作用，但妊娠期间生殖组织机械功能的改变显著地导致了与妊娠和分娩相关的并发症：(A)大多数产妇的分娩损伤是由于组织过度拉伸，(B)自发早产是由于组织结构完整性的丧失，以及(C)盆底疾病是由于组织支持的损害。在小鼠模型中，将使用最先进的实验方法来描述子宫、宫颈和阴道之间迷人的机械相互作用，无论是在体内还是在体外。其中包括数字图像相关的双轴充气测试、多光子显微镜、生物化学、三维超声和高精度磁共振成像技术。将开发一种新的本构框架来描述实验观察到的生殖器官的力学性能，包括怀孕和产后的显著重塑。将使用新的实验数据创建并验证高保真和稳健的有限元模型，以研究女性盆腔系统在怀孕和分娩期间的解剖复杂功能，为女性健康提供一种新的、非侵入性的风险检测方法。PIS将通过组织研讨会和会议，担任同行评议期刊特刊的客座编辑，以及出版各种类型的科学出版物，促进和促进工程和医疗专业人员之间充满活力的互动。这个CARE4HeR项目将支持为高中、本科生和研究生，特别是来自种族和少数民族的学生创造创新研究和独特的教育机会。这一CARE4HeR项目将打破生殖生物力学方面现有的竖井，简化研究操作，加快妇女生殖健康领域的进步和创新。新的资源，从尖端的实验方法到新的本构模型和高保真模拟工具，将被创造出来，可供工程和医学界使用，以满足美国妇女迫切的生殖健康需求。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The overall goal of this Leading Engineering for America's Prosperity, Health, and Infrastructure (LEAP-HI) Coordinated Advances in Reproductive Engineering for Health Research (CARE4HeR) project is to address the alarming healthcare challenges associated with pregnancy and childbirth by integrating novel and transformative approaches in experimental, theoretical, and computational mechanics. Pregnancy and childbirth can have tragic and devastating effects on the health, wellness, and quality of life of many women, children, and families. The maternal mortality rate in the United States (US) is rising, even as other developed countries experience a decline in pregnancy-related deaths. Preterm birth is very common: 500,000 babies are born preterm every year in the US. Complicated vaginal deliveries make up 16 percent of all childbirths in the US annually, and they represent primary risk factors for the development of pelvic floor disorders. These disorders affect 25 percent of all women, leading to not only physical pain but also social isolation, depression, anxiety, and sexual dysfunction. Large racial and ethnic disparities exist, with higher rates in maternal mortality and preterm birth among African Americans. Although several factors undoubtedly play a role, alterations of the mechanical function of reproductive tissues throughout pregnancy significantly contribute to pregnancy-related and childbirth-related complications: (a) most maternal birth injuries are due to excessive tissue stretching, (b) spontaneous preterm birth is attributed to loss of tissue structural integrity, and (c) pelvic floor disorders develop as a result of compromised tissue support.State-of-the-art experimental methods will be employed to characterize the fascinating mechanical interplay of the uterus, cervix, and vagina, both in vivo and ex vivo, in the murine model. These include biaxial inflation testing with digital image correlation, multiphoton microscopy, biochemistry, three-dimensional ultrasound, and high-precision magnetic resonance imaging techniques. A new constitutive framework will be developed to describe the experimentally-observed mechanical properties of reproductive organs, including the remarkable remodeling during pregnancy and postpartum. High-fidelity and robust finite element models will be created and validated using the new experimental data to study the anatomically complex function of the female pelvic system during pregnancy and parturition, offering a new, non-invasive risk detection method for women's health. The PIs will facilitate and nurture vibrant interactions among researchers in engineering and healthcare professionals by organizing symposia and conference sessions, serving as guest-editors for special issues in peer-reviewed journals, and publishing various types of scientific publications. This CARE4HeR project will support the creation of innovative research and unique educational opportunities for high school, undergraduate, and graduate students, especially from racial and ethnic minorities. This CARE4HeR project will break down the existing silos in reproductive biomechanics, streamlining research operations and accelerating progress and innovation in women’s reproductive health. New resources, ranging from cutting-edge experimental methodologies to novel constitutive models and high-fidelity simulation tools, will be created that can be used by both the engineering and medical communities to address the urgent US women’s reproductive health needs.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.