A proof-of-concept study on an injectable artificial ovary using xenogeneic ECM for fertility restoration

Abstract

The development of artificial ovaries presents a promising strategy for patients facing infertility due to chemotherapy or high metastatic potential cancers, where conventional ovarian tissue transplantation poses significant risks. Our study introduces an "injectable artificial ovary" leveraging a xenogeneic extracellular matrix (ECM) hydrogel derived from bovine ovarian tissue. The ECM hydrogel obtained from bovine ovaries and prepared through decellularization, milling, and digestion, is injectable and thermo-responsive, preserving the matrix structure without cytotoxicity. This innovative approach delivers a non-surgical alternative for fertility preservation by harnessing the bioactive and adaptable properties of ECM hydrogels to support ovarian follicle maturation and restore endocrine functions. In our results, the hydrogel demonstrated temperature-responsive gelation and biocompatibility, promoting follicle development and increasing 17β-Estradiol secretion. Such advancements highlight the potential for this technique to redefine fertility treatments and regenerative medicine. Notably, the in-situ development of ovarian follicles within the injected hydrogel preceded the successful ovulation after subcutaneous implantation. Our findings suggest that this approach could serve as a heterotopic artificial ovary, offering a promising solution for fertility preservation in patients with high metastasis risk cancers who cannot undergo conventional treatments. This strategy advances artificial ovary technologies, presenting new possibilities for reproductive health and fertility preservation interventions. 10 Artificial organ development encompasses various approaches. 11, 12 While electronic devices, such as artificial hearts and prosthetic limbs, have been commercialized, their relevance to tissue-based organ engineering, such as artificial ovaries, is