CAREER: Bioelectronically programmable scaffolds for controlling ovarian follicle growth dynamics

About This Grant

The functional cells in female ovaries are follicles, which are spherical aggregates of cells containing an immature egg. Follicles cannot be replenished, so the total number declines as some follicles are selected for growth every month. The remaining follicles remain dormant to preserve reproductive function over several decades. The mechanisms that determine which follicles are selected for growth and which remain dormant is poorly understood. A better understanding of these mechanisms could inform new treatments for infertility caused by polycystic ovary syndrome, cancer treatments, or aging. Studies suggest that changes in the stiffness of the follicle microenvironment may trigger follicle growth. The goal of this CAREER project is to investigate how dynamic stiffness influences follicle growth to interrogate this relationship. The project will use a new bioelectronic material that changes stiffness in response to an applied electric potential to modulate, study, and optimize mechanobiological functions of ovarian follicles. The project will support grade 6-12 outreach activities and curricula in biomaterials engineering as well as undergraduate learning modules, all to support increased participation in STEM fields. This CAREER project will investigate how dynamic stiffness of the microenvironment of ovarian follicles influences their growth characteristics. Extracellular matrix stiffness spatially varies in the ovaries and these different regions are associated with different follicle growth phenotypes. It is hypothesized that when follicles observe a decreased stiffness, cell signaling pathways are disrupted and dormant follicles are activated to a growing state. However, there are no material systems available that can present defined mechanical stimuli to follicles in a cytocompatible fashion. The goal of this proposal is to develop a biomaterial platform to investigate how microenvironment stiffness dynamics result in changes to follicle growth rates and the corresponding cell signaling pathways. Conducting polymers will be used to develop 3D bioelectronic scaffolds that change matrix stiffness in response to an applied electrical potential. The research objectives include (1) to define processing-property-function relationships of conducting polymers to optimize the stiffness range to match the ovarian microenvironment, (2) to determine cell signaling changes of ovarian cells in response to dynamic matrix stiffness in 2D culture, and (3) to determine if dynamic stiffness programs can control follicle growth rates using 3D printed microporous scaffolds. The outcome of this project will be a novel tool for the field of mechanobiology. 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.