Scaffold-based biomaterials in ovarian tissue engineering

Abstract

The rapid evolution of reproductive tissue engineering has positioned biomaterials as key enabling tools for the development of artificial ovary technologies aimed at fertility preservation and ovarian function restoration. Conventional assisted reproductive technologies mainly target late-stage folliculogenesis and remain inadequate for conditions involving early follicle depletion, such as gonadotoxic cancer therapies and premature ovarian insufficiency. This systematic review, conducted in accordance with PRISMA 2020 guidelines, critically examines biomimetic scaffold strategies for ovarian tissue engineering, focusing on material composition, structural design, biofunctionality and translational relevance. A total of 137 studies were analysed, covering in vitro and in vivo applications of gel-like hydrogels, decellularized extracellular matrix-derived scaffolds, electrospun fibrous constructs and 3D-printed architectures. Natural and ECM-based materials provide tissue-specific biological cues but are limited by variability and mechanical instability, whereas synthetic scaffolds, particularly electrospun poly(ε-caprolactone), offer superior control over architecture, reproducibility and scalability, supporting follicle survival across multiple mammalian models. Overall, hybrid biomaterial strategies integrating biological activity with engineered scaffold tunability emerge as the most promising platforms for artificial ovary development, while standardization and translational validation remain key challenges.