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. 2021 Jul 10;9:198–220. doi: 10.1016/j.bioactmat.2021.07.005

Table 4.

Angiogenesis/vasculogenesis on-a-chip.

Hydrogel types Cell sources Organoid types Vascular morphology/signals Major results Ref.
Fibrin HUVECs, lung FBs Microvascular Complex perfusable microvascular networks Diseased vessel diameter by adding VEGF or increasing fibrinogen concentration [123]
Fibrin HUVECs, lung FBs, pericytes, hGMCs Complex angiogenic sprouts and primary vessel network. Spatially controlled co-culture of HUVECs with different cell types Interconnected vasculogenic networks due to the co-culture of lung FBs; formation of a gradient of LF-secreted factors to induce angiogenic sprouting; simulation pericyte recruitment from interstitial tissue; mimicking of tumor vasculatures [181]
Fibrin HUVECs, hMSCs Microvascular networks Calculation of the size of microvascular networks, average vessel diameters, and length of branches for HUVECs only and co-culture condition Generation of a non-interconnected microvasculature with the addition of TGF-β1; promotion of functional networks with the addition of Ang-1; reduction of mean vessel diameter and increased number of network branches with the presence of mural cells [184]
Gelatin, fibrin HUVECs, hMSCs, hNDFs Osteogenic differentiation HUVEC-lined vascular channel The viability of hNDFs decreased at distance more than 1 mm from the embedded vasculature; differentiation of hMSCs to an osteogenic lineage [186]
Collagen HUVECs, NIH/3T3 Vasculature The confluent monolayers within the channels about 200 μm Two endothelialized tubules within a stromal compartment; generation of spatially defined VEGF, bFGF, and phorbol myristate acetate gradients; investigations of invasion depth and sprouting morphology induced by GF gradients [33]
PEGMA, PEGDA, GelMA, SPELA HUVECs, MC3T3 Microchannel networks 150–1000 μm diameters of microchannel using various dispensing capillaries Enhanced mass transport, differentiation, cellular viability within the constructs due to the presence of GelMA; proliferation of HUVECs at high GelMA concentration. [187]
Collagen, gelatin HUVECs, C2C12 cells Vascularized muscle bundle Microchannel at 500 μm in diameter Formation of robust HUVEC-junction in 24 h; immediate HUVEC-sprouting with a muscle fiber; longer length of vessel sprouting in vascularized muscle bundle compared with the group without muscle bindle. [188]

Abbreviations: bFGF - basic fibroblast growth factors, C2C12 cells - mouse myoblasts, FBs - fibroblasts, GelMA - gelatin methacrylate, hGMCs - human glioblastoma multiforme cells, hMSCs - human marrow mesenchymal stem cells, hNDFs - human neonatal dermal fibroblasts, HUVECs - human umbilical vein endothelial cells, MC3T3 - mouse embryonic osteoblasts precursor cells, NIH/3T3 - mouse embryonic fibroblasts, PEGDA - poly(ethylene glycol) diacrylate, PEGMA - poly(ethylene glycol) dimethacrylate, SPELA - lactide-chain-extended star polyethylene glycol.