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Table 3 Organ-on-a-chip for modeling the pathophysiology of female reproductive system diseases

From: Organ-on-a-chip: future of female reproductive pathophysiological models

Model category

Cell types

Culture environment

Device characteristics

Culture characteristics

Significance

Year/Reference

Placenta-on-a-Chip

λ HUVECs

λ BeWo

λ Medium: HUVECs: ECM medium; BeWo: DMEM/F-12 medium;

λ Temperature: 37 °C; CO2: 5%

λ The upper and lower layers with microchannels: 1.5 cm×1.5 mm×400 μm

λ Transparent semipermeable membrane: 0.4 μm pores

λ Device material: PDMS

λ Fabrication method: soft lithography technology

λ Flow rate: 10 µl/h

λ Coating: 0.1 mg/mL Collagen I

Placental inflammation model

2018/ [114]

Placenta-on-a-Chip

λ HUVECs

λ BeWo

λ Medium: HUVECs: endothelial cell growth medium; BeWo: Ham’s F-12 K nutrient mixture + 10% FBS + 40 mg/mL gentamicin

λ Temperature: 37 °C; CO2: 5%

λ Three channels: 300 μm wide and 220 μm high

λ Device material: PDMS

λ Fabrication method: soft lithography technology

λ Flow rate: /

λ Coating: ECM gel

Placental inflammation model

2022/ [115]

Amnion membrane organ-on-chip

λ hiPSC

λ Medium: mTesR1 medium

λ Temperature: 37 °C; CO2: 5%

λ Two parallel medium channels: 1 × 0.5 × 1.4mm3

λ The middle matrix channel: 1 × 0.2 × 1.4mm3

λ Device material: PDMS

λ Fabrication method: soft lithography technology

λ Flow rate: 1 µl/h

λ Coating: Matrigel

Amniotic inflammation model

2020/ [122]

Amnion membrane organ-on-chip

λ Primary AECs

λ Primary AMCs

λ Medium: AECs: Ham’s F-12/DMEM + 10% FBS + 10 ng/ml EGF + 2 mM L-glutamine + 100 U/ml penicillin G + 100 mg/ml streptomycin; AMCs: complete DMEM-F12 medium + 5% FBS + 100 U/ml penicillin G + 100 mg/ml streptomycin

λ Temperature: 37 °C; CO2: 5%

λ The first layer: 5 μm deep

λ The second layer: 500 μm thick

λ Device material: PDMS

λ Fabrication method: soft lithography technology

λ Flow rate: /

λ Coating: type IV collagen matrigel

Oxidative stress model

2019/ [116]

Amnion membrane organ-on-chip

λ AECs

λ Decidual cells

λ Medium: AECs: Ditto; Decidual cells: Ham’s F-12/DMEM + 5% FBS + 10 ng/mL EGF + 100 U/ml penicillin G + 100 mg/ml streptomycin

λ Temperature: 37 °C; CO2: 5%

λ Two microfluidic chambers: 4.75 mm×6.2 mm

λ A semipermeable polycarbonate membrane

λ Device material: PDMS

λ Fabrication method: soft lithography technology

λ Flow rate: /

λ Coating: Matrigel

Oxidative stress model

2020/ [117]

Feto-maternal interface organ-on-chip

λ AECs

λ Decidua cells

λ CTs

λ AMCs

λ Medium: AECs: Ditto; Decidual cells: Ditto; CTs: Ham’s F12/DMEM + 10% FBS + 100 U/mL penicillin G + 100 mg/mL streptomycin; AMCs: DMEM-F12 medium + 5% FBS + 100U/mL penicillin G + 100 mg/mL streptomycin

λ Temperature: 37 °C; CO2: 5%

λ Chamber 1: decidual cells, 250 μm in height, 3000 μm in width

λ Chamber 2: fetal CTs and CMCs, 250 μm in height, 2000 μm in width

λ Chamber 3: AMCs, 250 μm in height, 2000 μm in width

λ Chamber 4: AECs, 250 μm in height, 600 μm in width

λ Device material: PDMS

λ Fabrication method: soft lithography technology

λ Flow rate: /

λ Coating: type IV collagen

Maternal infection model

2020/ [118]

Feto-maternal interface organ-on-chip

λ Ditto

λ Ditto

λ Ditto

λ Ditto

Environmental toxin exposure model at the feto-maternal interface

2022/ [119]

Feto-maternal interface organ-on-chip

λ hFM_AEC

λ hFM_DEC

λ hFM_CTC

λ hFM_AMC

λ Medium: hFM_AEC: KSFM + 30 µg/mL bovine pituitary extract + 0.1 ng/mL EGF + 0.4 mM CaCl2 + 0.5 mg/mL primocin; hFM_DEC: DMEM/F-12 + 10%FBS + 10% penicillin/streptomycin + 10% amphotericin B; hFM_CTC: DMEM/F-12 + 0.20% FBS + 0.01 mM β-mercaptoethanol + 0.5% penicillin/streptomycin + 0.3% BSA + 1× ITS-X + 2 µM CHIR99021 + 0.05 µM A83-01 + 1.5 µg/mL L-ascorbic acid + 50 ng/mL EGF + 0.08 mM VPA + 1×Revitacell; hFM_AMC: DMEM/F-12 + 5% FBS + 10% penicillin/streptomycin + 10% amphotericin B

λ Temperature: 37 °C; CO2: 5%

λ Ditto

λ Ditto

Oxidative stress model at the feto-maternal interface

2023/ [120]

Amniotic fluid organ-on-a-chip

λ Amniotic fluid

λ Human fetal brain cell

λ Medium: Human fetal brain cell: ATCC-formulated Eagle’s Minimum Essential Medium + 10% FBS

λ Temperature: 37 °C; CO2: 5%

λ The first microchannel layer: 600 × 30 × 5µm3

λ The second cell culture chamber layer: 500 μm deep

λ Device material: PDMS

λ Fabrication method: soft lithography technology

λ Flow rate: /

λ Coating: type IV collagen

Fetal neuroinflammation model

2022/ [121]

OvCa-Chip

λ A2780

λ HUVECs

λ /

λ The top tumor channel: 400 μm wide, 100 μm high

λ The bottom vascular channel: 400 μm wide, 100 μm high; 20 mm long

λ Device material: PDMS

λ Fabrication method: soft lithography technology

λ Flow rate: 0.5 µL/min

λ Coating: collagen-fibronectin

Ovarian cancer-vascular-blood model

2020/ [19]

OvCa-Chip

λ HOMECs

λ A2780

λ Medium: HOMECs: RPMI 1640 + 100 U/ml penicillin + 100 µg/ml streptomycin; A2780: RPMI 1640 + 100 U/ml penicillin + 100 µg/ml streptomycin

λ Temperature: 37 °C; CO2: 5%

λ The top portion of the device was changed from a single microchannel (1 mm×1 mm×100 μm) to three parallel microchannels

λ Each micropillar: 250 × 100 × 100µm3

λ Device material: PDMS

λ Fabrication method: soft lithography technology

λ Flow rate: /

λ Coating: collagen I

Ovarian tumor microenvironment chip

2021/ [128]

Endometriosis organ-on-a-chip

λ ESCs

λ HPMCs

λ Medium: ESCs: DMEM + 10% FBS + 2000 u penicillin + streptomycin + glutamine; HPMCs: complete medium

λ Temperature: 37 °C; CO2: 5%

λ The microchannels: 1.5 cm×300 μm×300 μm

λ Device material: PDMS

λ Fabrication method: /

λ Flow rate: /

λ Coating: /

Pathological model of peritoneal endometriosis

2012/ [14]

Endometriosis organ-on-a-chip

λ 12Z cells

λ Medium: DMEM-F12 medium

λ Temperature: 37 °C; CO2: 5%

λ Device features: /

λ Device material: PDMS

λ Fabrication method: soft lithography technology

λ Flow rate: /

λ Coating: collagen hydrogel

Organotypic organ-on-a-chip luminal model for endometriosis

2023/ [137]

  1. Notes: AMCs, amnion mesenchymal cells; AECs, amnion epithelial cells; FBS, fetal bovine serum; EGF, epidermal growth factor; CTs, chorion trophoblasts; hFM_AEC, human amnion epithelial cells; hFM_DEC, human maternal decidual cells; hFM_CTC, human chorion trophoblast cells; hFM_AMC, human amnion mesenchymal cells; ESCs, Endometrial stromal cells; HPMCs, Human peritoneum mesothelial cells.