March 18
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12:00 PM
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1:00 PM
Engineering Biomimetic Materials for Female Reproductive and Gynecologic Health
Samantha Zambuto, PhD
T32 Postdoctoral Fellow
Washington University School of Medicine
Washington University in St. Louis
Abstract:
Female reproductive and gynecologic health are historically understudied fields that would significantly benefit from engineering expertise due to the unique biomechanical environment in the female reproductive tract and the dynamic tissue changes orchestrated throughout the menstrual cycle by sex hormones. With the synergistic techniques of tissue engineering, biomaterials science, biomechanics, and reproductive biology, we engineer models of the female reproductive system, including the endometrium, decidua, and vagina, to study pregnancy-related disorders and birth injuries. We use these tissue engineering models to understand cell-cell interactions, cell-matrix interactions, and hormone dynamics in the context of early pregnancy and vaginal tearing during childbirth. To mimic, instruct, and define the cellular microenvironment in the female reproductive tract, we use gelatin methacryloyl (GelMA) hydrogels. Derived from gelatin, GelMA hydrogels are biomimetic, biocompatible, and bioactive. Functionalization of gelatin into GelMA renders GelMA stability under physiological temperatures as well as enhanced tunability of mechanical properties. We fabricated a library of GelMA hydrogels and composites that capture a range of biomechanical properties specifically designed to mimic tissue biomechanical properties. We then construct GelMA hydrogel composites by combining GelMA hydrogels with other materials, including electrospun fibers and hyaluronic acid methacrylate. We perform sophisticated material characterization with spherical nanoindentation and define the effects of biomechanical properties on cellular behavior and the effect of cells on hydrogel mechanical properties. We demonstrated that GelMA hydrogel platforms are adaptable for studying dynamic endometrial processes, including endometrial angiogenesis, hormone responsiveness (e.g., decidualization of endometrial stromal cells), epithelial monolayer formation in a stratified tissue model, and trophoblast invasion. We also established a three-dimensional model of the vaginal epithelium by incorporating primary human vaginal epithelial cells in gelatin-elastin fiber composites impregnated with GelMA hydrogels. Our ongoing studies seek to advance these existing model systems into complex, three-dimensional tissue mimics of the endometrium and vagina for not only basic science purposes but also for regenerative medicine applications.
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