Table 1 Overview and characteristics of current BBB-on-chips models
From: In vitro modeling of the neurovascular unit: advances in the field
Date published | Microvessel/endothelial compartment size | Material and membrane | Biological coating | Endothelial cell type | Additional cells in co-culture (type) | Barrier permeability tracer | Permeability measurement (cm/s) | TEER (Ω cm2) | Shear stress (dyne/cm2) | Ref# |
|---|---|---|---|---|---|---|---|---|---|---|
2019 | Microfluidic device (200 μM width, 100 μM height) | PDMS | Human fibronectin (300 μg/ml) | Immortalized human cerebrovascular endothelial cells (hcmec\D3) | Astrocytes cultured in basolateral compartment | 10 kDa and 70 kDa FITC dextran | 10 kDa FITC dextran: 15 × 10−6 cm/s 70 kDa FITC dextran: 3.7 × 10−6 cm/s | NA | 2.73 | [143] |
2019 | 150 μM | PDMS | Collagen type IV and Fibronectin | BMECs derived from human iPSCs | N/A | Lucifer yellow, Alexa 647 conjugated 10 kDa dextran | Lucifer yellow: 5–6 × 10−7 Alexa 647 conjugated 10 kDa dextran: below detection limit | 2000–4000 | 1 | [144] |
2019 | (Two channels) 2 cm long and 1 mm wide; top and bottom channels were 1 and 0.2 mm high | PDMS), 2-channel, separated from a parallel vascular microchannel by a porous (2 μm diameter), polyethylene terephthalate (PET) membrane | Collagen type IV and fibronectin | iPS-BMVECs | Primary human pericytes and astrocytes | Fluorescent labeled of dextran tracers (3, 10, or 70 kDa) | 8.9, 1.1, and 0.24 × 10−8 cm/s for 3,10, and 70 kDa | 24,000a | 6 | [70] |
2019 | 150 μm | Collagen type 1 rat (hydrogel) | Collagen type IV and fibronectin | iPS-BMVECs | NA | Lucifer yellow, Rhodamine 123 (R123), and 10 kDa dextran | LY = 2.84 ± 0.41 × 10−7 cm/s R123 = 1.32 ± 0.16 × 10−7 cm/s The permeability of 10 kDa dextran in dhBMEC microvessels was below the detection limit | NA | 4 | [71] |
2019 | Cylindrical template rod (150 μm) | Collagen type 1 rat hydrogel | Collagen type IV and fibronectin | Human iPSC-ECs | Human iPSC-pericyte | Lucifer yellow, and 10 kDa dextran | LY = 4 × 10−7 cm/s The permeability of 10 kDa dextran was below the detection limit | NA | 4 | [145] |
2018 | Self orgnized less than 100 μm | Fibrin gel | Fibronectin | Human iPSC-ECs | Primary human pericytes and astrocytes | 40 and 10 kDa FTIC-dextrans | Of 8.9 × 10−8 cm/s and 2.2 × 10−7 cm/s for 40 kDa and 10 kDa FTICdextran, | NA | NA | [146] |
2017 | Microfluidic chip with fluidic channels (190 μM height and 920 μM width) | PDMS, hydrogel channel is 580 μM wide while the fluidic channel is 920 μM wide. Endothelial cells seeded in the fluid channels. Astrocyte and Neurons mixed in collagen-1 and perfused in the hydrogel channels | Poly-d-Lysine | HUVEC or hcmec\D3 | Primary cortical neuron from rat, primary astrocytes from rat | 10 kDa Oregon green 488 dextran, 70 kDa Texas red dextran | 10 kDa Oregon green 488 dextran in HUVEC: 7 × 10−5 cm/s 70 kDa Texas Red Dextran in HUVEC: 5 × 10−5 cm/s 10 kDa Oregon green 488 dextran in hcmec\D3: 1 × 10−5 cm/s 70 kDa Texas Red Dextran in hcmec\D3: 0.25 × 10−5 cm/s | NA | NA | [73] |
2017 | Microfluidic device (width 2 mm and height of 0.2, 0.6 and 1 mm) | PDMS with polyester membrane (0.4 μM) | Fibronectin solution | Immortalized mouse endothelial cells (Bend3) | Immortalized mouse pericytes adhering to polyester membrane on 2nd channel and mouse astrocyte type I clone on the bottom of 2nd channel | 10 kDa Oregon green 488 dextran 70 kDa Texas red dextran | Monoculture: HUVEC: 7 × 10−5 cm/s (10 kDa), 5 × 10−5 cm/s (70 kDa) hcmec\D3 | Single culture: ~ 134 Bi culture: ~ 260 Triculture: ~ 310 | NA | [147] |
2017 | (300 μm * 160μm) | Polycarbonate insert with 04 μm pore size | Collagen type IV and fibronectin | Human iPSC-ECs | Rat primary astrocytes | 4, 20 and 70 KDa FITC-dextrans | 4 kDa = 10−7 and 20 and 70 was close to10−8 cm/s | 2000–4000 | 0.25 | [72] |
2017 | 180 μm cylindrical rod | Collagen type I hydrogel in PDMS | Collagen | (hCMEC/D3) | Human astrocytes | 4 kDa FITC-dextran | 0.8 × 10−6 cm/s | 200-1000 | 0.5 | [148] |
2016 | PDMS with collagen hydrogel inside (1 mm * 1 mm) | Collagen type 1 rat | NA | Primary human endothelial cells | Primary human pericytes and astrocytes | 3 kDa fluorescent dextran | 2–4 × 10−6 cm/s | NA | 1 | [149] |
2016 | Two rectangular PDMS channels with 3.7 cm × 0.2 cm × 0.2 cm size | Polycarbonate membrane with a thickness of 23 μm and a pore size 0.45 μm | Rat tail collagen | hCMEC/D3 | NA | Sodium fluorescein (376 Da), 4 kDa FITC-dextran, f Evans blue-labeled albumin (67 kDa) | Sodium fluorescein = 1.57 × 10−6cm/s 4 kDa Dextran = 1.32 × 10−6 Evans blue = 0.15 × 10−6cm/s | 28 | 0.15 | [150] |
2016 | Two rectangular PDMS channels with 3.7 cm × 0.2 cm × 0.2 cm size | Polycarbonate membrane with a thickness of 23 μm and a pore size 0.45 μm | Rat tail collagen | Primary rat brain endothelial cells | Rat primary pericytes and astroglia | Sodium fluorescein (376 Da), 4 kDa FITC-dextran, f Evans blue-labeled albumin (67 kDa) | Sodium fluorescein = 1.15 × 10−6cm/s 4 kDa Dextran = 0.20 × 10−6 Evans blue = 0.04 × 10−6cm/s | 114.2 | 0.15 | [150] |
2015 | Microfluidic chip with vascular channel having 100 μM height | PDMS, 0.2 μM Polycarbonate membrane | Laminin | Primary hBMVEC | Primary astrocytes, and pericytes plus neurons differentiated from hiPSCs | 10 kDa and 70 kDa FITC Dextran | Not measured. Only absolute fluorescence measured | Custom built impedance measurement (~ 12,000a) | NA | [96] |
2015 | 3D printed vessels having 235 and 260 μM diameters | 3D co-printing Vero White Plus-FullCure 835 resin as main framework and poly-vinyl alcohol (PVA) as a dissolvable support material | Fibronectin | Bend3 cells | N/A | 40 kDa FITC dextran | 2.27 × 10−7 cm/s | NA | NA | [151] |
2015 | Rectangular PDMS channel (6.3 mm × 100 μm) | PDMS | Fibronectin | Neonatal rat brain capillary endothelial cells | Primary cultures of neonatal rat astrocytes | 10 and 70 kDa fluorescent dextran | 2.9 ± 1.0 × 10−6 | 150-180 | 3.8 × 10−3 | [152] |
2015 | Rectangular PDMS channel (1 mm × 150 μm) | PDMS | Collagen IV–fibronectin | bEnd3 | Immortalized mouse astrocyte C8D1A | 70 KDa dextran | 5.9 × 10−7 cm/s | NA | 5 | [153] |
2013 | Rectangular PDMS channel (200 μm × 100 μm) | PDMS | Fibronectin | Rat brain EC (RBE4 cells) | N/A | 3 and 5 KD FITC-dextran | Relative comparison only | NA | NA | [154] |
2013 | PDMS channel (100 μM × 500 μM) | PDMS | Fibronectin | Rat brain EC (RBE4 cells) | E18 rat cortical cells | 3 kDa Alexa fluor-dextran | Relative comparison only | NA | NA | [155] |
2012 | Rectangular PDMS channel with a length of 1 cm, a width of 500 μm and a depth of 100 μm | Polycarbonate membrane with a thickness of 10 μm and a pore size of 0.4 μm | Rat collagen type I | (hCMEC/D3) | N/A | N/A | N/A | 120 | 5.8 | [156] |
2011 | 11 hollow polypropylene fibers (600 ± 90 μM) inside a sealed chamber (the extraluminal space) accessible by ports | Polypropylene with transcapillary pores (2 to 4 μM) | Fibronectin | Normal adult human brain microvascular endothelial cells | Human adult astrocytes | Sucrose, phenytoin and diazepam | Sucrose: 3.16 × 10−6, phenytoin: 6.75 × 10−5, diazepam: 6.88 × 10−3 cm/s | ~ 500 on the 21st day | 4 | [157] |
2002 | 11 hollow polypropylene fibers (600 ± 90 μM) inside a sealed chamber (the extraluminal space) accessible by ports | Polypropylene hollow fiber apparatus with 12 μM pores | Fibronectin | Bovine aortic endothelial cells (BAEC) | Rat glial cell tumor line | N/A | N/A | 500 | NA | [90] |