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    Dorian G. Luijkx, et al. *Monochorionic Twinning in Bioengineered Human Embryo Model*, Advanced Materials (2024). DOI: 10.1002/adma.202313306

    https://onlinelibrary.wiley.com/doi/pdf/10.1002/adma.202313306

    **Abstract**

    Monochorionic twinning of human embryos increases the risk of complications during pregnancy. The
    rarity of such twinning events, combined with ethical constraints in human embryo research, makes
    investigating the mechanisms behind twinning practically infeasible. As a result, there is a significant
    knowledge gap regarding the origins and early phenotypic presentation of monochorionic twin
    embryos.

    In this study, a microthermoformed-based microwell screening platform is used to identify
    conditions that efficiently induce monochorionic twins in human stem cell-based blastocyst models, termed ‘twin blastoids’. These twin blastoids contain a cystic GATA3+ trophectoderm-like epithelium encasing two distinct inner cell masses (ICMs).

    Morphological and morphokinetic analyses reveal that twinning occurs during the cavitation phase via splitting of the OCT4+ pluripotent core. Notably, each ICM in twin blastoids contains its own NR2F2+ polar trophectoderm-like region, ready for implantation.

    This is functionally tested in a microfluidic chip-based implantation assay with epithelial endometrium cells. Under defined flow regimes, twin blastoids show increased adhesion capacity compared to singleton blastoids, suggestive of increased implantation potential.

    In conclusion, the development of technology enabling large-scale formation of twin blastoids, coupled with high sensitivity readout capabilities, presents an unprecedented opportunity for systematically exploring monochorionic twin formation and its impact on embryonic development.

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