Recapitulation of folliculogenesis to ovulation in a biomimetic micro-cavity ovary

Abstract Ovary disease is a major cause of female infertility and could disrupt the hormone balance, which may cause multi-organ disorders in the long-term effect. However, conventional artificial ovary techniques usually encapsulate follicles in 3D hydrogels and block the ovulation ability. In this study, we fabricated a biomimetic micro-cavity ovary by a microsphere-templated technique to recapitulate the ovulation process, where sacrificial gelatin microspheres were mixed with photo-crosslinkable gelatin methacryloyl (GelMA) to engineer an open cavity niche for follicle growth. The microcavity’s parameters were optimized to be suitable for follicle growth. With that, we showed that the micro-cavity ovary could support the follicle growth to antral stage and the ovulation of meiosis-matured oocytes out of the micro-cavity ovary without extra manipulation. The ovulated oocyte was characterized in a great quality. This technique would be of great advantage to be further applied in clinics that recover natural conception after in vivo transplantation of the biomimetic ovary.