3D Printed Ovaries that Work are Now Science Fact not Science Fiction
An all-female team of researchers at Northwestern University Feinberg School of Medicine and McCormick School of Engineering recently made history by successfully using 3-dimensional (3-D) printing to bioengineer functional prosthetic ovaries which were implanted in mice and allowed ovulation and impregnation to take place. This breakthrough shows promise for eventual use in humans in the treatment of infertility.
The collaboration of several experts was required to design, engineer, and overcome structural and biological compatibility issues in order to build a true bioprosthesis. “The goal,” said Teresa K. Woodruff, a reproductive scientist and director of the Women’s Health Research Institute at Feinberg, “was to restore fertility and endocrine health to young cancer patients who have been sterilized by their cancer treatment.”
The two biggest hurdles the teams faced were determining what biological material would have the tensile strength and rigidity to withstand manipulation and surgical implantation within a live mammal, and what geometric structure would be the best architecture for the scaffolding or “skeleton” of the ovary which would house the delicate mouse egg follicles and ensure survival.
What is unique about this research is the architecture of the scaffold and the material, or “ink,” the scientists are using, said Ramille Shah, assistant professor of materials science and engineering at McCormick and of surgery at Feinberg.
The most viable biologic material or “ink” to use in the 3-D printing process proved to be a hydrogel designed by breaking down collagen which is the fibrous extracellular protein matrix underlying most of the structures of the body. “The great advantage of using gelatin over collagen is that is much easier to process but still has the same bioactivity as collagen,” said Alexandra Rutz, PhD and former biomedical engineering graduate fellow in Shah’s Tissue Engineering and Additive Manufacturing (TEAM) lab at the Simpson Querrey Institute.
The next hurdle was to theorize and build a porous and layered geometric pattern or weave which would make up the scaffolding or structure of the bioprosthetic and provide dimensionality. The pores would need to naturally interact with the mouse tissues and circulation, and, would house the different cell types. This differentiation of cell structure would boost hormonal function and enable a viable and functional organ.
Rutz, who is now a Whitaker International Postdoctoral Scholar at École Des Mines De Saint-Étienne in Gardanne, France explained, ““3-D printing is done by depositing filaments. You can control the distance between those filaments, as well as the advancing angle between layers, and that would give us different pore sizes and different pore geometries.””
The two teams are the first scientists to successfully imagine and orchestrate a self-supported functional geometric structure as well as engineer an appropriate biogel from which to build the 3-dimensional design. The geometric design directly affected whether or not the ovarian follicles, organized hormone-producing support cells surrounding an immature egg cell, would survive in the ovary.
“Without a 3-D platform”, said Shah, “we wouldn’t have been able to demonstrate that scaffold architecture makes a difference in follicle survival.”
Impact on Future Human Bioengineering
Monica Laronda, co-lead author of this study and a former post-doctoral fellow in the Woodruff lab, said, “The purpose of this scaffold is to recapitulate how an ovary would function. We’re thinking big picture, meaning every stage of the girl’s life, so puberty through adulthood to a natural menopause.”
Laronda, who is now an assistant professor at the Stanley Manne Children’s Research Institute at the Ann & Robert H. Lurie Children’s Hospital believes this research will have a significant impact on future developments in soft tissue regenerative medicine and will provide hope in restoring fertility to many women who have been unable to conceive.