CAREER: Growth and Remodeling of the Uterine Cervix During Pregnancy

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This NSF Faculty Early Career Development (CAREER) Program award will characterize the biomechanical mechanisms that cause preterm birth (PTB) and will train the next generation of female engineers with educational activities geared towards Women's Health. Despite advances in prenatal care, the rate of PTB (birth before 37 weeks of gestation) in the United States remains high. This fact underscores how little is known about the causes of PTB, which is a leading cause of death in children under five. Researchers do know that the cervix, a cylindrical organ located at the base of the uterus, is a critical mechanical barrier to maintain the baby to full term. Then, at time of delivery the cervix is instructed by hormonal cues to remodel, soften, and dilate to become a safe passage for the baby. If this cervical tissue remodeling timing is off, PTB can occur due to premature cervical dilation. The understanding of this cervical remodeling process is limited because there are no engineering tools to characterize normal and abnormal cervical softening. To address this need, this study will measure the mechanical and biochemical property changes of the cervix under various hormonal cues and derive a set of equations that can predict the mechanical function of the cervix during pregnancy. This study will bring an improved understanding to the underlying causes of PTB related to cervical dysfunction, and will be an essential step toward the development of rational therapies to prevent PTB.This CAREER study will derive a constitutive material modeling framework for the growth and remodeling of the cervix during pregnancy. The main goal is to determine the driving factors that cause premature cervical remodeling and the mechanical dysfunction of the cervix. The modeling framework will be based on the evidence that levels of estrogen and progesterone play a key role in regulating cervical tissue composition during pregnancy. Cervical tissue will be modeled as a hydrated fiber composite porous material where the interstitial pore space allows for the growth and removal of solid mass. The associated material parameters will evolve as a function of hormone-mediated extracelluar matrix compositional state variables. Model functions will be based on mechanical and collagen characterization of gestation-timed cervical tissue samples taken from established mouse models of hormone-mediated normal, preterm, and disrupted cervical remodeling. These equations will be validated by assessing their predictive capability of the material response to loading and hormonally-driven tissue changes.