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. 2021 Aug 5;8(19):2100798. doi: 10.1002/advs.202100798

Table 2.

Summary of case studies for microfluidic‐based vascularization strategies

Vascularization method Organ/tissue model Vessel caliber (d)/channel size (h × w) Channel shape Chip composition Cellular composition Perfusion parameters Duration of in vitro study In vivo evaluation/drug testing Refs.
Soft lithography Liver 100 µm × 1 mm Rectangular, straight PDMS; PE (polyester) membrane LSECs, HCs, KCs, HSCs (all primary from mouse) 0.1 or 0.5 dynes cm−2, syringe pump 1 day No/No [ 73 ]
BBB
  • Vascular channel: 800 µm, vascular network: <50 µm

  • 35–100 µm

Rectangular, straight
  • PDMS; fibrin hydrogel

  • PDMS; fibrin‐hyaluronic acid

  • HUVECs, lung fibroblasts, rat cortex neural cells

  • Brain microvascular ECs; HUVECs; pericytes; astrocytes

7 days No/No [ 66 , 88 ]
Kidney 0.2 × 1 mm (vascular), 1 × 1 mm (urinary) Rectangular, straight PDMS (chip, membrane) Glomerular ECs; hIPS‐derived podocytes 0.017 dynes cm−2 (vascular), 0.0007 dynes cm−2 (urinary), peristaltic pump 8 days No/Yes [ 64 ]
Intestine 0.15 × 1 mm Rectangular, straight PDMS (chip, membrane) Capillary ECs or lymphatic microvascular ECs, Caco‐2 intestinal epithelial cells, immune cells 0.02 dynes cm−2 >7 days No/Yes [ 70 ]
Multiorgan (100 × 500 µm) to 40 µm Rectangular, curved PDMS Dermal microvascular ECs 10–40 dynes cm−2, on‐chip micropump Up to 4 weeks No/No [ 78 ]
Templating Liver
  • 300 µm (main channel)

  • 100–1000 µm

  • Circular, straight

  • Circular, curved, branched

  • Collagen I

  • GelMA

  • HUVECs; hepatocytes (HepG2); MSCs

  • HUVECs, hepatocytes (HepG2)

  • 10−1 dynes cm−2, peristaltic pump

  • 50 µL h−1, syringe pump

  • 8 days

  • 7 days

  • No/No

  • No/Yes

[ 19 , 103 ]
Skin
  • 520 µm

  • 100–250 µm

  • Circular

  • Rectangular, curved, branched

  • Collagen I

  • Collagen I

  • HUVECs, dermal fibroblasts, epidermal keratinocytes

  • HUVECs, iPSC‐derived ECs, dermal fibroblasts, keratinocytes

  • 2–3 mL h−1, peristaltic pump

  • Syringe pump

  • 10 days

  • 21 days for cornification, 2 days at ALI

  • No/Yes

  • Yes/No

[ 74 , 94 ]
Heart 100–500 µm Circular Fibrin matrix Neonatal rat heart cells mix 20 µL h−1, syringe pump 21 days No/No [ 93 ]
3D bioprinting Urothelial/vascular tissue a) ≈700 µm (inner), ≈1 mm (outer) Circular, multilayer, flexible Bioink: PEGOA + GelMA Urothelial: human urothelial cells + human bladder SMCs; vascular: HUVECs + human SMCs 14–21 days No/No [ 104 ]
Kidney 200 µm Circular, colocalized Gelatin + fibrin ECM; bioink: pluronic F127 + PEO Glomerular microvascular ECs; proximal tubule epithelial cells 0.3 dynes cm−2 18 days No/Yes [ 75 ]
Heart 500 µm (200–900 µm) Circular, hierarchical, multibranched Agarose hydrogel, PCL network Rat cardomiocytes Syringe pump 5 days Yes/No [ 99 ]
Vasculature a) 1.5 × 3 mm Rectangular, straight PMMA case, GelMA Aortic ECs; aortic SMCs; fibroblasts 100 µL h−1, peristaltic pump 7 days No/No [ 105 ]
Alternative strategies LbL Liver/heart 100 × 50 to 100 µm Rectangular, straight POMaC, fibrin gel/Matrigel for parenchyma Liver: HUVECs + hESC‐derived hepatocytes + hMSCs; heart: HUVECs + hESC‐derived CMs + hMSCs 0.6 dynes cm−2, bioreactor 7 days Yes/Yes [ 69 , 100 ]
Laser‐based <10 µm Tortuous, dense PEGDA Mouse brain ECs 10 µL min−1 11 days No/No [ 101 ]
Explanted vessels Brain 120 µm Circular, physiological PDMS ECs, SMCs 0.5 µL min−1, no external pump No/Yes [ 102 ]
a)

Bioinks containing cells.