Artificial ovary systems for fertility preservation: Current advances, bioengineering strategies, and translational...

Ovarian insufficiency is a significant cause of infertility and endocrine problems in women, especially after premature ovarian failure or gonadotoxic cancer treatments. Traditional fertility preservation methods, such as oocyte and ovarian tissue cryopreservation, are still limited by follicular loss, ischemic injury, and the risk of reintroducing malignant cells. To address these issues, researchers have been developing the artificial ovary, a bioengineered system designed to mimic the natural ovarian environment and restore hormonal and reproductive functions. This review aimed to critically examine current evidence and recent advances in the development of artificial ovaries. A structured literature search was conducted across PubMed, Scopus, and Web of Science covering the period 2020-2025, using the following keywords: "artificial ovary," "ovarian tissue engineering," "folliculogenesis in vitro," "bioprinting," and "reproductive biomaterials." Although a broader body of literature exists in this area, approximately 100 publications were initially identified. From these, 65 peer-reviewed articles were selected for detailed analysis based on predefined inclusion criteria, including direct relevance to artificial ovary development, experimental or translational significance, transparent methodology, and outcomes related to follicle viability or endocrine function. The results were divided into three main areas: cellular components granulosa, theca, and stem cell- derived ovarian cells; biomaterials and scaffolds natural materials like collagen, fibrin, alginate, and decellularised extracellular matrix (ECM), as well as synthetic matrices such as PEG (Polyethene glycol), PLGA (poly lactic- co- glycolic acid), and PVA (polyvinyl alcohol); and emerging bioengineering techniques-3 D bioprinting, microfluidic "ovary- on- a- chip" systems, and organoid culture models. The studies reviewed show promising results in follicle survival, hormone secretion, and partial folliculogenesis, though complete oocyte maturation and functional vascularisation remain significant challenges. Ultimately, the field of artificial ovary is a pioneering, rapidly advancing area that integrates tissue engineering and reproductive medicine. Ongoing interdisciplinary collaboration and long-term preclinical studies are vital for translating this technology into clinical practice for fertility preservation and hormonal restoration.