Using a 3D printer, Dr Laronda and colleagues designed a scaffold made of gelatin, a derivative of collagen. They developed several pocket-type designs for the scaffolds. Drawing on human models, they tested several different architectures.
“We found that the follicles preferred more contact points, that they want room in order to grow from a small size up to 20 mm, but they also like to feel stuck,” said Dr Laronda. “So, the sphere itself is maintained so those support cells are surrounded by the oocyte and maintaining those necessary connections, yet the other cells are anchoring the scaffold and spreading and really filling this in, which is the ideal way to engineer an organ. You want the native cells to be taking over.”
Once they developed the structure, the researchers implanted the ovary bioprosthesis with green fluorescent protein follicles in mice whose ovaries were removed. Results showed that these transplant recipients gave birth to live pups. These pups expressed the green fluorescence, indicating that the eggs that were released, fertilized, and implanted into the uterus came exclusively from the transplanted prosthesis.
Moreover, data showed that the mice were able to support the pups via lactation until weaning, and vaginal histology indicated that their estrous cycle was restored after implantation.
Dr Laronda noted that studies in larger animal models are in development to evaluate potential side effects of implantation such as inflammation or transplant rejection. Clinical grade techniques and a clinical grade scaffold are also being developed. The use of a 3D printer to create the bioprosthesis allows the researchers to scale up the model and use various materials, she explained.
“I hope that I’ve shown that we are moving toward an answer for that young girl who has preserved her ovary in hopes of restoring her fertility and hormone function as after she has survived her disease,” Dr Laronda concluded.
- Laronda M, Rutz AL, Xiao S, Whelan KA, Shah RN, Woodruff TK. LB-OR1-1: A 3D Printed Ovarian Bioprosthesis Restores Estrous Cyclicity and Supports Natural Ovulation, Live Birth and Lactation. Presented at: ENDO 2016; April 1-4, 2016; Boston, MA.