Bioengineering strategies and material innovations for artificial ovary construction: progress, challenges, and...

Artificial ovary (AO) construction is a promising approach for restoring fertility and endocrine function in patients with ovarian insufficiency caused by aging, gonadotoxic cancer treatments, or genetic and autoimmune disorders. Despite substantial experimental progress, the clinical readiness of available AO material platforms remains unclear. This review systematically evaluates biomaterials and construction strategies used in AO development, with emphasis on the relationship between material properties, biological performance, and translational potential. A total of 116 original studies published between 1990 and 2025 were analyzed using a tiered evidence framework (Tiers 0-5), ranging from material characterization to long-term endocrine restoration or live birth. Natural biomaterials generally support early follicular survival but are limited by mechanical instability and variability, whereas synthetic platforms offer improved reproducibility yet require biofunctionalization. Composite systems increasingly achieve advanced outcomes by addressing follicular expansion, vascularization, and immune compatibility. Key barriers to clinical translation include vascular integration, long-term function, GMP compliance, and regulatory feasibility. This review provides an evidence-based framework to guide clinically relevant AO development.