Bioengineering of Ovarian Tissue for Fertility Restoration

Advances in bioengineering of ovarian tissue offer new avenues for fertility restoration in individuals facing ovarian insufficiency due to cancer treatment, genetic disorders or natural decline. Central to this effort is the recreation of the ovarian microenvironment to support follicle survival, growth and endocrine function. Strategies encompass decellularised scaffolds derived from native ovarian extracellular matrix, synthetic and hybrid hydrogels tailored to match biomechanical properties, and three-dimensional printed or electrospun matrices designed to optimise pore architecture and vascular integration. Stem cell–derived organoids and induced pluripotent stem cell approaches seek to replenish both germ and somatic cell lineages, enabling in vitro maturation and disease modelling. Injectable cell–laden constructs further promise minimally invasive delivery of hormone-producing cells for therapeutic hormone restoration. These complementary technologies interweave advances in biomaterials, tissue engineering and reproductive biology, and have demonstrated efficacy in preclinical models, achieving folliculogenesis, vascularisation and in some cases live births. The translation of these platforms holds global relevance for oncofertility, hormonal health and regenerative medicine, heralding a shift towards personalised and safe fertility preservation.

Research from Nature Portfolio

Recent studies have employed additive manufacturing to fabricate microporous hydrogel scaffolds with controlled pore geometry, demonstrating that scaffold architecture critically influences follicle survival and vascular integration, ultimately restoring ovarian function and enabling natural fertility in mouse models. Patterned electrospun fibrous scaffolds have likewise been shown to mimic the native fibrillar extracellular matrix, supporting the adhesion and spherical morphology of porcine follicles without impairing development. Foundational work with designer fibrin-based grafts encapsulating isolated primordial follicles has produced live births in a murine infertility model, underscoring the potential of biomaterial grafts for isolating follicle-based fertility preservation.

Bioengineering of Ovarian Tissue for Fertility Restoration publication trend

The graph below shows the total number of articles in bioengineering of ovarian tissue for fertility restoration across all publications each year (not limited to Nature Index journals).

Technical terms

Scaffold: A three-dimensional structure that provides mechanical support and a matrix for cell attachment and tissue formation.

Hydrogel: A water-swollen polymer network used as a biomaterial to mimic soft tissue environments.

Folliculogenesis: The maturation process of ovarian follicles from primordial to preovulatory stages.

Preantral follicle: An early developmental stage of the ovarian follicle before the formation of an antrum.

Organoid: A miniaturised and simplified three-dimensional tissue model grown in vitro from stem cells that recapitulates organ-specific functions.

Extracellular matrix (ECM): The complex network of proteins and polysaccharides that surround cells and provide structural and biochemical support.

Induced pluripotent stem cells (iPSCs): Somatic cells reprogrammed to an embryonic-like state capable of differentiating into various cell types.

PEGylation: The chemical modification of a molecule or surface with polyethylene glycol to enhance stability and biocompatibility.

Granulosa cell: Ovarian somatic cell type that surrounds the oocyte and produces sex steroids essential for follicle development.

Theca cell: Ovarian somatic cell layer external to granulosa cells that synthesises androgens used as precursors for oestrogen production.

References

1. A bioprosthetic ovary created using 3D printed microporous scaffolds restores ovarian function in sterilized mice. Nature Communications (2017).
2. Electrospun patterned porous scaffolds for the support of ovarian follicles growth: a feasibility study. Scientific Reports (2019).
3. Primordial Follicle Transplantation within Designer Biomaterial Grafts Produce Live Births in a Mouse Infertility Model. Scientific Reports (2015).
4. Mind the mechanical strength: tailoring a 3D matrix to encapsulate isolated human preantral follicles. Human Reproduction Open (2023).
5. Research advances in the construction of stem cell-derived ovarian organoids. Stem Cell Research & Therapy (2024).
6. Injectable Biomimetic Hydrogel Constructs for Cell-Based Menopausal Hormone Therapy with Reduced Breast Cancer Potential. Biomaterials Research (2024).