Elastic Fiber Regeneration Potential During Postpartum Healing

这项工作将通过测量产后愈合过程中弹性纤维再生的潜力，以及这种潜力如何随母亲的年龄变化来推动科学进步。弹性纤维可以在怀孕期间再生，以适应成长中的胎儿。在产后康复期间，这也有利于母亲。然而，随着母亲年龄的增长，这些弹性纤维的再生能力可能会下降。这可能会导致并发症，如盆底疾病。该奖项将支持基础研究，以更好地了解女性生殖系统中弹性纤维再生在产后愈合期间和随年龄增长的变化。该奖项还将开发一种新的数学模型来描述弹性纤维再生如何控制组织功能。这些弹性纤维对大多数软生物组织的功能至关重要。因此，这个模型也可以用来更好地理解其他软组织的力学行为，这些软组织包括弹性纤维，如肺、血管或皮肤。此外，数学模型将告诉我们，我们通过研究产后愈合所获得的结果是否可以用于识别旨在治疗并最终预防因其他组织弹性纤维断裂而出现的医学问题的疗法。这个项目的研究成果将被纳入桌面棋盘游戏，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。弹性纤维对生物组织动态平衡至关重要，因为它们不仅提供弹性和回弹力，还可能在物理上捆绑生物组织中决定功能的细胞和其他蛋白质。先前的工作表明，产后愈合过程中弹性纤维的再生和重塑对维持生殖组织健康至关重要。产后愈合和衰老过程中弹性纤维的组成和与其他细胞和蛋白质的相对排列尚不清楚。因此，该奖项将决定弹性纤维如何决定衰老和产后愈合过程中生物组织微结构和机械功能的演变。特别是，弹性纤维相对于细胞和其他生物蛋白质的进化方向和相对排列将被量化并直接纳入新的数学模型，以更好地理解弹性纤维再生如何决定组织的收缩能力和功能。这将通过：1)建立和验证描述随着产妇年龄增加的阴道细胞外基质、力学和收缩能力的生物力学模型；以及2)确定产妇年龄对产后愈合期间弹性纤维再生和力学性能演变的影响。该奖项反映了NSF的法定使命，并通过使用基金会的智力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 work will promote the progress of science by measuring the potential of elastic fibers to regenerate during postpartum healing and how this potential varies with the age of the mother. Elastic fibers may regenerate during pregnancy to accommodate the growing fetus. This also benefits the mother during postpartum healing. However, the ability of these elastic fibers to regenerate may decrease as the mother ages. This may cause complications such as pelvic floor disorders. This award will support fundamental research to better understand how elastic fiber regeneration in the female reproductive system changes during postpartum healing and with aging. This award will also develop a new mathematical model to describe how elastic fiber regeneration controls tissue function. These elastic fibers are critical to the function of most soft biological tissues. Therefore, this model may also be used to better understand the mechanical behavior of other soft tissues that elastic fibers, such as the lungs, blood vessels, or skin. Further, the mathematical model will tell us if the results we learn by studying postpartum healing can be used to identify therapies that aim to treat, and ultimately prevent, medical problems that arise due to disrupted elastic fibers in other tissues. Research findings from this project will be incorporated into a tabletop board game, teaching modules for K-12 education, and into undergraduate and graduate biomedical engineering courses.Elastic fibers are critical for biological tissue homeostasis as they not only provide resilience and recoil but may also physically tether cells and other proteins within biological tissues that dictate function. Prior work suggests that regeneration and remodeling of elastic fibers during postpartum healing is critical to maintaining reproductive tissue health. Elastic fiber composition and relative arrangement to other cells and proteins during postpartum healing and aging is unknown. Therefore, this award will determine how elastic fibers dictate the evolving biological tissue microstructure and mechanical function during aging and postpartum healing. In particular, the evolving orientation and relative arrangement of elastic fibers with respect to cells and other biological proteins will be quantified and directly incorporated into a new mathematical model to better understand how elastic fiber regeneration dictates tissue contractility and function. This will be accomplished by: 1) Formulating and validating a biomechanical model that describes the vaginal extracellular matrix, mechanics, and contractility with increasing maternal age; and 2) Determining the effect of maternal age on elastic fiber regeneration and evolving mechanical properties during postpartum healing.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.