Session: Rising Stars of Mechanical Engineering Celebration & Showcase

Paper Number: 148076

148076 - Computational Models of Soft Tissue Growth and Remodeling During Pregnancy 

Introduction: Pregnancy subjects the maternal body to significant changes. For example, the maternal heart works harder to support the mother and the growing fetus, increasing cardiac output by 45%; the uterus grows by increasing its mass 15-fold and its cavity volume 1000-fold. Maternal soft tissues grow and remodel to meet this increased physiological demand. Timely growth and remodeling (G&R) and mechanical function of maternal soft tissues are critical for a healthy pregnancy. The uterus must remain relaxed as it grows and stretches to prevent a preterm birth. The maternal heart grows by 30-40% in mass and volume to meet the cardiovascular demand, but sometimes, this growth is pathological and can lead to heart failure towards the end of pregnancy or in the postpartum period.

Contributions: Approximately 10,000 babies are born daily in the United States – yet our basic scientific knowledge of pregnancy is limited. Pregnancy research falls decades behind other well-studied fields like cardiovascular science or orthopedics. Critical questions surrounding normal and complicated pregnancies remain unanswered. As a result, preterm birth and maternal mortality rates continue to rise, and heart problems remain the number one cause of pregnancy-related deaths. Therefore, my research focuses on understanding the mechanisms that drive maternal soft tissue growth, remodeling, and mechanical function. Specifically, we combine rigorous engineering mechanics with computational systems biology to study the interactions between mechanical and biological signaling that affect maternal soft tissue biomechanics and mechanobiology during pregnancy and postpartum. 

Methodology and results: My lab focuses on the maternal cardiovascular system and the uterus. Here, we highlight some of our latest work and accomplishments.

Cardiac growth during pregnancy: I previously built a multiscale cardiac growth model that simulates hormonal and hemodynamic changes during pregnancy to predict heart growth during pregnancy in rats. This model couples a cell-signaling network model of cardiomyocyte (heart muscle cell) growth to an organ-level cardiac growth model. The signaling model simulates hormonal and cell-level stretch changes, while the cardiac growth model simulates ventricular growth (change in unloaded geometry) and hemodynamic changes. My initial work demonstrated this model can predict heart growth during an uncomplicated rat pregnancy. We recently tested the breadth of our model and showed it could capture additional heart growth associated with hypertensive pregnancies in rats. We have also demonstrated that allometrically scaling the compartmental model can correctly predict heart growth in pregnant mice and humans with uncomplicated pregnancies. Further, incorporating mouse-specific anatomy and physiology in the model is sufficient for predicting animal-specific heart growth, suggesting the exciting precision-medicine potential of our model. 

Uterine growth and remodeling during pregnancy: Previously, we quantified cervical remodeling and demonstrated a 4-order magnitude decrease in stiffness during an 18-day mouse gestation. In contrast, our planar biaxial tensile tests on the mouse uterus demonstrate that while the toe region of the stress-strain curves increases significantly during pregnancy, the maximum stiffness in the linear region does not change with gestation. We also developed a method to connect in vivo mechanical states with the ex vivo data by tracking and defining unloaded and in situ stretches. In parallel, we are creating an innovative finite element model of uterine growth and remodeling of the mouse uterus. Specifically, we account for remodeling (change in active and passive and active mechanical properties), growth (change in unloaded geometry), and deformations due to pup growth. Our preliminary analysis of this model shows that passive remodeling, rather than growth, affects how much the uterus can contract at the end of pregnancy.

 

Presenting Author: Kyoko Yoshida University of Minnesota

Presenting Author Biography: Dr. Kyoko Yoshida, Ph.D., is an Assistant Professor in the Department of Biomedical Engineering at the University of Minnesota. She previously completed her postdoctoral training at the University of Virginia. She obtained her Ph.D. in Mechanical Engineering from Columbia University as an NSF Graduate Research Fellow and her B.S. in Mechanical Engineering from the University of Notre Dame. Her research focuses on the growth and remodeling biomechanics of soft tissues, including the cervix, uterus, and heart. Specifically, she uses computational and experimental approaches to understand how mechanical and hormonal signaling interact to control maternal soft tissue adaptations during pregnancy to support both mother and baby for a healthy pregnancy. Her research is supported by the NSF CAREER and the American Heart Association's Career Development Award.

Authors:

Kyoko Yoshida University of Minnesota