TABLE 2.
Representative MPS placental models.
| Model | Main application | Microfluidic setup and flow parameters | Model and contribution to placental relevance |
|---|---|---|---|
| Placenta-on-chip __ (Cao et al., 2024) |
Model of transport and toxicology (nanoparticle (NP) exposure-related fetal risk) | - Setup: Transwell® plate with porous membrane culture inserts, common lower (fetal) channel - Flow: Rocking platform (10 rpm, ±8° tilt angle, bidirectional flow) |
- Model: Human trophoblast stem cells (hTSCs) differentiated into STs, and human umbilical vein endothelial cells (HUVECs) on either side of a membrane. Addition of differentiated THP-1 monocytes to the hTSC side - Relevance: Model mimicked placenta villi structural architecture and barrier function. hTSCs differentiated into syncytiotrophoblasts (STB) under continuous fluid flow; Captured inflammatory response |
| Placenta-on-chip __ (Lermant et al., 2024) |
Barrier integrity for transport assays | - Setup: OrganoPlate® (Mimetas) in CO2 incubator - Flow: Programmable rocking platform (7° tilt angle, 8-min cycles, bidirectional flow) |
- Model: On-chip differentiation of hiPSC cells into trophoblasts - Relevance: 3-D tubule development; Structural barrier formed under flow in direct contact with an ECM gel in the absence of a physical barrier, allows environment interactions |
| Placenta-on-chip __ (Vidal et al., 2024) |
Drugs and pollutants affecting pre-term birth (endocrine- disrupting compounds, e.g., bisphenols, and pollutants, e.g., cigarette smoke extract) | - Setup: PDMS chip made by soft lithography. Seven channels with lateral microchannel connections - Flow: Hydrostatic pressure; Gradients made using volume differentials, from 2:1 to 1.2:1, inlets: outlet; Unidirectional |
- Model: Endothelial cells (PVECs, HUVECs) and primary cells (placental trophoblasts differentiated into STs, decidua, and placental stroma) in interconnected channels to create multiple interfaces (2nd trimester mimic); Addition of THP-1 macrophages in the stromal chamber - Relevance: Improved placental architecture, multicellular interactions; Captured CT invasion, endocrine production, barrier function and inflammatory response to oxidative stress |
| Placental barrier and FMi-on-chip __ (Safarzadeh et al., 2024) |
Model pregnancy pathology and preclinical drug trial platform | - Setup: PDMS chip fabrication by soft lithography; Seven channels with lateral microchannel connections - Flow: Hydrostatic pressure. Reservoir differentials used for gradients; Unidirectional flow |
- Model: Primary human fetal membrane cells (amnion epithelial, amnion mesenchymal and chorion trophoblast), decidua cells, BeWo cells to mimic placental trophoblasts (differentiated into STs), and HUVECs in interconnected channels - Relevance: Maintained intercellular interactions, interfaces, in utero layer thicknesses; Enabled dynamic molecular diffusion; Captured inflammatory response |
| Placental barrier-on-chip __ (Abostait et al., 2022) |
Model of trophoblast differentiation and NP uptake (impact of flow, shear stress and trophoblast syncytialization on NP uptake) | - Setup: ibidi chip (μSlide I0.4 Luer) - Flow: Pressure- driven flow controller (Elveflow); Flow rate 22.9 μL/min, shear stress 0.025 dyn/cm2 Microvilli formation used 0.014 dyn/cm2; Unidirectional flow |
- Model: Single channel cultured with BeWo cells; Comparison of static and in-flow conditions - Relevance: Flow promoted syncytialization and microvilli formation; Flow dynamics and degree of trophoblast syncytialization affect cell uptake of liposomes |
| Placental syncytium-on-chip __ (Delon et al., 2025) |
Model of trophoblast differentiation (comparison of chemically versus mechanically induced syncytialization) | - Setup: Membrane- integrated recirculating organ-on-chip (MIROoC; patent pending); PET membrane between 2 stacked channels - Flow: Rocking platform (15° tilt angle, 0.3–6 rpm); Flow rate 1.5–27.5 μL/min, shear stress 0.023–0.75 dyn/cm2; Bi- and unidirectional flow |
- Model: BeWo cell line differentiated into STs and HUVEC cultures on either side of a permeable membrane; Comparison of static and in-flow conditions - Relevance: Physiologically relevant placental syncytium-on-chip without need for chemical (forskolin)-induced differentiation; BeWo cells differentiated into STs with flow (wall shear stress 0.1 dyn/cm2); Captured cell fusion, polarization, barrier function, human chorionic gonadotropin secretion, and expression of key transporters |
| Placenta-on-chip __ (Jeong et al., 2024) |
Model of early pregnancy in hypoxic environment (placenta development, trophoblast invasion) | - Setup: PDMS chip made by soft lithography; Two channels, connected by microchannels. In hypoxia chamber (2% oxygen) - Flow: Sustained perfusion not reported; Medium replaced every 12 h |
- Model: Human first-trimester cytotrophoblast (HTR-8/SVneo) cell line, HUVECs lining a lumen of collagen I gel in an interconnected channel - Relevance: Improved geometry. Multi-channel 3-D model, including a vascular lumen of round cross-section; Captures tight junction formation in vessel structure, barrier function, trophoblast invasion and oxygen tension |
| Placenta-on-chip __ (Ghorbanpour et al., 2023) |
Model of placentation in preeclampsia conditions for biomarker discovery and drug screening | - Setup: AIM Biotech chip with 3 laterally-aligned channels, made of COP thermoplastic - Flow: Interstitial flow using hydrostatic pressure gradients (volume differential of 2:1, top:bottom inlets); Medium changed every 24 h |
- Model: First trimester trophoblast cell line (ACH-3P) in one side channel, HUVECs in collagen I gel in the interconnected central channel - Relevance: Representative model of the early placenta; Captures trophoblast migration and invasion and hallmarks of vascular dysfunction in preeclampsia, including upregulation of anti-angiogenesis and inflammatory- related proteins, and impaired vascular network development |
| Placental barrier-on-chip __ (Rabussier et al., 2023) |
Model of placentation in preeclampsia and hypoxia conditions for drug transport and screening | - Setup: OrganoPlate® 3-lane 40 (Mimetas) in a low oxygen (1%) CO2 incubator - Flow: Programmable rocking platform (7° tilt angle, 8-min cycles, bidirectional flow) |
- Model: BeWo cells differentiated into STs, and HUVECs in the outer channels, separated by central collagen I/IV layer - Relevance: Captures functional syncytium with barrier properties, polarization, secretion of relevant extracellular membrane components, thinning of the maternal-fetal space, hormone secretion, and transporter function; Captures preeclampsia features of reduced barrier function, hormonal secretion, brush border formation and increased nuclei count; Suitable for assay standardization |
| Implantation-on-chip __ (Park et al., 2022) |
Model of FMi for trophoblast invasion and spiral artery remodeling during implantation and early pregnancy | - Setup: PDMS chip fabricated by soft lithography; Three laterally-aligned channels including a central channel for a capillary-pinned hydrogel barrier - Flow: Intentionally kept static to mimic occluded maternal vessels due to trophoblast plugs in the first trimester; Compatible with perfusion if needed |
- Model: Primary extravillous trophoblasts (EVTs) isolated from first-trimester tissue, and uterine ECs in outer channels, connected via a collagen I channel ± decidualized primary stromal cells (DSCs) and/or uterine NK cells - Relevance: Improved 3-D microarchitecture, relative spatial arrangement of maternal and fetal elements, and maintenance of cell proliferative ability; Captures critical aspects of human implantation and early placentation such as migration of early trophoblasts towards maternal spiral arteries |
| Placenta-on-chip __ (Lee et al., 2016) |
Model FMi for molecular transport and exchange studies | - Setup: PDMS chip made by soft lithography; Two stacked channels separated by a vitrified collagen membrane - Flow: continuous withdrawal of medium at 30 μL/h using a syringe pump |
- Model: HUVECs, JEG-3 trophoblast cell line cultured on either side of a membrane - Relevance: Improved structural and functional features of FMi including co-culture, compartmentalization, dimensionality, barrier formation; Captures glucose permeability and transport |
| Placental organoid-on-chip __ (Wang et al., 2025b) |
Model placental physiology, placenta-related gestational diseases and viral infection | - Setup: polycarbonate KabellyInsert™ chip resembling a transwell plate modified for basal channel flow and culture inserts with porous PET membranes - Flow: Rocking platform for vascular channel perfusion using gravity-driven flow (2 rpm, 6-s cycle; bidirectional) |
- Model: hTSC-derived trophoblast organoids or EVT organoids made from hTSC aggregates embedded in Matrigel in the transwell insert, with HUVEC cells cultured on the membrane underside - Relevance: Improved structural and functional features of human early hemochorial placenta, including trophoblast epithelium layer and intravillous fetal capillaries, long-term trophoblast proliferation, differentiation, and viability; Captures dynamic transport in a paracrine manner, activation of innate immune-related signaling pathways and immunomodulatory factor secretion |