biostudies-literatureRichards CNational Heart Foundation of Australia (Heart Foundation)8267https://www.ebi.ac.uk/biostudies/studies/S-EPMC12432263biostudies-literatureUnknown16(1)Trophoblast organoids can provide crucial insights into mechanisms of placentation, however their potential is limited by highly variable extracellular matrices unable to reflect in vivo tissues. Here, we present a bioprinted placental organoid model, generated using the first trimester trophoblast cell line, ACH-3P, and a synthetic polyethylene glycol (PEG) matrix. Bioprinted or Matrigel-embedded organoids differentiate spontaneously from cytotrophoblasts into two major subtypes: extravillous trophoblasts (EVTs) and syncytiotrophoblasts (STBs). Bioprinted organoids are driven towards EVT differentiation and show close similarity with early human placenta or primary trophoblast organoids. Inflammation inhibits proliferation and STBs within bioprinted organoids, which aspirin or metformin (Nature communicationsMatrix directs trophoblast differentiation in a bioprinted organoid model of early placental development.PMC12432263106628Ghosh AMcGrath KCHansbro PMPadula MPMcClements LBannister AChen HVolkerling ABottomley ALRichards CGallego-Ortega DCole LO'Rourke MOwen GGorrie CAfalseMatrix directs trophoblast differentiation in a bioprinted organoid model of early placental development.Trophoblast organoids can provide crucial insights into mechanisms of placentation, however their potential is limited by highly variable extracellular matrices unable to reflect in vivo tissues. Here, we present a bioprinted placental organoid model, generated using the first trimester trophoblast cell line, ACH-3P, and a synthetic polyethylene glycol (PEG) matrix. Bioprinted or Matrigel-embedded organoids differentiate spontaneously from cytotrophoblasts into two major subtypes: extravillous trophoblasts (EVTs) and syncytiotrophoblasts (STBs). Bioprinted organoids are driven towards EVT differentiation and show close similarity with early human placenta or primary trophoblast organoids. Inflammation inhibits proliferation and STBs within bioprinted organoids, which aspirin or metformin (2025-01-01T00:00:00Z2025 Sep2026-06-02T08:46:40.832Z2026-04-16T03:13:00.807ZS-EPMC124322634094033710.1038/s41467-025-62996-0