2026 Theses Doctoral

A Multiscale, Spatial Biomechanical Atlas of the Uterus in Pregnancy and Gynecologic Disease

Fodera, Daniella M.

The uterus is a mechanically dynamic, spatially heterogeneous organ that undergoes profound structural and functional transformations across the reproductive lifespan. Still, its biomechanical behavior remains poorly quantified across distinct tissue layers, throughout pregnancy, and within disease contexts. This dissertation establishes a multiscale, spatial biomechanical atlas of the uterus, integrating structural, compositional, and mechanical measurements across length scales, to reveal how physiologic and pathologic remodeling define and shape uterine mechanical behavior.

Micro-mechanical characterization of the human uterus across distinct tissue layers demonstrates that the uterine wall behaves as a mechanical gradient, from the innermost endometrium layer through the myometrium to the outermost perimetrium. In pregnancy, the uterine wall undergoes selective mechanical adaptations within the small strain regime; the endometrium/decidua becomes stiffer and less viscous, while the myometrium and perimetrium maintain values comparable to those in nonpregnancy. Further, a cross-species comparative analysis of uterine tissue layers between humans and non-human primates reveals marked similarities in the mechanical properties of the myometrium across gestation, with notable divergences observed for the endometrium/decidua and perimetrium layers.

In the context of gynecologic disease, uterine fibroids exhibited distinct mechanical and structural features relative to patient-matched myometrium tissues. At the microscale, fibroids were found to be stiffer and less permeable compared to the myometrium regardless of tumor size, with notable distinctions in collagen content and organization. Further, spatial maps of the uterine fibroid-myometrium interface revealed distinct mechanical transitions in stiffness and permeability, accompanied by circumferential alterations in myometrial fiber alignment surrounding the tumor. Under large deformation, fibroids were substantially stiffer and less extensible than the myometrium, but exhibited equivalent ultimate tensile strength and fracture toughness. Taken together, the uterus demonstrates fundamental biomechanical phenomena: time-dependence, anisotropy, nonlinearity, and tension-compression asymmetry.

Collectively, this dissertation offers the most comprehensive, spatially resolved, multiscale biomechanical characterization of the uterus to date across reproductive states and disease contexts. The resulting dataset offers a quantitative foundation for future research avenues in mechanobiology, computational modeling, biomaterial design, and translational research efforts aimed at improving women’s reproductive health.