CAREER: Determining the Dynamic Role of Elastic Fibers in Cervovaginal Adaptations

该学院早期职业发展计划(CALEAR)项目将支持一项综合研究和教育计划，以确定弹性纤维在女性生殖系统软组织中的作用。弹性纤维存在于大多数柔软的生物组织中，对组织功能至关重要。弹性纤维的丧失可能会导致女性盆底严重的健康问题，并导致早产和盆腔器官脱垂。该项目将开发一种计算机模型，可以预测女性生殖系统软组织中的弹性纤维如何随着机械压力的变化而变化。这将有助于通过确定怀孕期间和其他改变组织机械压力的正常事件期间组织属性变化的原因来促进健康。这些知识和新的计算机建模工具也可以用来理解其他含有弹性纤维的软组织，如肺、血管、皮肤和消化系统在施加机械压力后会发生什么变化。这个项目的研究成果将被纳入手机游戏，K-12教育的教学模块，以及本科生和研究生的生物医学工程课程。一个经过实验验证的计算模型将被用来确定弹性纤维为什么以及如何影响生物组织中的机械生物学适应。这将通过：1)利用机械负荷组织培养系统，确定弹性纤维在宫颈阴道组织中随负荷变化而演变的双向机械特性和收缩能力的作用；2)建立描述宫颈阴道机械特性、收缩能力和细胞外基质组成的生物力学生长和重塑模型，描述有和没有受损弹性纤维的宫颈阴道机械特性、收缩和细胞外基质组成；以及3)通过预测宫颈阴道对机械负荷变化的适应的关键特征来验证该模型。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。

This Faculty Early Career Development Program (CAREER) project will support an integrated research and education program to determine the role of elastic fibers in the soft tissues of the female reproductive system. Elastic fibers are present in most soft biological tissues and are critical to tissue function. Loss of elastic fibers may contribute to significant health problems of the female pelvic floor and lead to preterm birth and pelvic organ prolapse. This project will develop a computer model that can predict how elastic fibers in the soft tissues of the female reproductive system change in response to mechanical pressure. This will help to advance health by determining causes for changes in the tissue properties during pregnancy and during other normal events that change tissue mechanical pressure. The knowledge and new computer modeling tools could also be used to understand how other soft tissues containing elastic fibers such as the lungs, blood vessels, skin, and the digestive system change as the result of applied mechanical pressure. Research findings from this project will be incorporated into a mobile telephone game, teaching modules for K-12 education and into undergraduate and graduate biomedical engineering courses.An experimentally-validated computational model will be used to determine why and how elastic fibers influence mechanobiological adaptations in biological tissues. This will be accomplished by: 1) Determining the role of elastic fibers in evolving biaxial mechanical properties and contractility in cervovaginal tissue in response to altered loads in situ using a mechanical loading tissue culture system; 2) Formulating a biomechanical growth and remodeling model that describes cervovaginal mechanical properties, contractility, and extracellular matrix composition with and without compromised elastic fibers; and 3) Validating the model by predicting the key features of cervovaginal adaptations in response to altered mechanical loading.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.