Bioelectronic material may help to reveal new information behind infertility

During a woman’s reproductive years, ovarian follicles containing an immature egg are recruited monthly for growth and development while others stay on reserve for years or even decades, yet researchers aren’t clear how this selection is made. More information about this selection process could lead to new understanding of infertility in women due to polycystic ovary syndrome (PCOS) or developing new fertility options for patients experiencing infertility due to cancer treatment and aging and to potential treatments.

With a five-year, $630,000 CAREER Award from the National Science Foundation, Alexandra Rutz, assistant professor of biomedical engineering in the McKelvey School of Engineering at Washington University in St. Louis, plans to take a mechanobiology approach to shed light on this process by investigating how the dynamic stiffness of the microenvironment of ovarian follicles determines which are selected for growth.

CAREER awards support junior faculty who model the role of teacher-scholar through outstanding research, excellence in education and the integration of education and research within the context of the mission of their organization. At least one-third of current McKelvey Engineering faculty have received the award.

Rutz and her team plan to use electronically conducting polymers to create 3D bioelectronic scaffolds that change stiffness in response to applied electricity. This biomaterial platform is expected to show how stiffness in the ovarian microenvironment results in changes to follicle growth rates and cell signaling pathways, said Rutz, who is collaborating with Farners Amargant i Riera, assistant professor of obstetrics & gynecology at WashU Medicine. Amargant i Riera studies mechanisms, like mechanical cues, that define the egg quality of follicles. The two researchers are also working together on a Collaboration Initiation Grant from the Center for Women's Health Engineering. 

“We are looking to determine whether the dynamic stiffness programming can control follicle growth rates using 3D-printed microporous scaffolds,” Rutz said. “We plan to create a novel tool for mechanobiology and to be the first researchers to investigate the effects of controllable dynamic stiffness in ovarian biology.” 

Ovarian tissue has a stiff outer layer where the resting follicles are generally found and a softer inner layer where the growing follicles are found. Patients with PCOS have stiffer tissue, often resulting in fertility issues.

“My lab will develop a stimulus-responsive biomaterial to deliver an external input,” Rutz explained. “In our case, that's going to be an electrical stimulation. and it will cause a stiffness change in the material — going from soft to stiff or stiff to soft — and then we will investigate how that changes the follicle.”

Rutz said the small, gentle electrical potentials will be safe for the cells, and the biggest hurdle will be developing the platform. She and members of her lab will rely on their previous work using 3D scaffolds in culture. 

Rutz has several invention disclosures and patent applications on file with the Office of Technology Management, including on this work.

In addition to the research, the project will include outreach activities and curricula in women’s health biomaterials engineering for teachers of middle and high school students. Rutz also plans to develop learning modules for undergraduate students, both for the classroom and in her lab, as well as to mentor students in summer research programs at WashU.

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