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

该学院早期职业发展计划（Career）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出现严重的健康问题，并导致早产和盆腔器官脱垂。该项目将开发一个计算机模型，可以预测女性生殖系统软组织中的弹性纤维如何响应机械压力而变化。这将有助于通过确定怀孕期间组织特性变化的原因和其他正常事件中改变组织机械压力的原因来促进健康。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，在施加机械压力的情况下是如何变化的。该项目的研究成果将被纳入手机游戏、K-12教育教学模块以及本科和研究生生物医学工程课程。一个经过实验验证的计算模型将用于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。这将通过以下方式实现：1)利用机械加载组织培养系统确定弹性纤维在响应改变的原位载荷时，在演变的双轴力学性能和宫颈阴道组织收缩性中的作用；2)建立生物力学生长和重塑模型，描述弹性纤维受损和不受损时颈阴道的力学特性、收缩性和细胞外基质组成；3)通过预测宫颈阴道适应改变机械负荷的关键特征来验证模型。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值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.