Table 5.
Modeling disease models by hydrogels with vasculatures for drug screening.
| Hydrogel types | Cell sources | Organoid types | Vascular morphology/signals | Major results | Ref. |
|---|---|---|---|---|---|
| GelMA, alginate | HUVECs, cardiomyocytes | Cardiac tissues | Migration of HUVECs and formation of a layer of confluent endothelium | The generation of aligned myocardium; dose-dependent responses of DOX towards HUVECs and cardiomyocytes | [49] |
| GelMA, PEGDA, alginate, PEGOA | MCF-7 cells, HUVECs, HLECs | Blood and lymphatic vessel pair | Perfusable blood vessels and lymphatic vessel with one blinded end | Adjusting levels of DOX diffusion using different combinations of lymphatic and blood vessels; increased IC50 value of DOX in 3D model | [51] |
| Gelatin, fibrin | ECFC-ECs, multiple tumor cell types (MCF-7, MDA-MB-231, SW620, SW480, and MNT-1) | Vascularized microtumors | Appearance of vessel-like fragments and complete networks within 3 d and 7 d, respectively | Enhanced angiogenic sprouting and vascular leakage in the vascularized microtumors with the presence of tumor cells; significant differences in IC50 for oxaliplatin between micro-tumors and 2D cultures | [198] |
| Collagen | HUVECs | Vascular sprouting | Active and rapid migration of HUVECs into hydrogel with VEGF | Diffusion of VEGF (40 ng mL−1) for mimicking pro-angiogenic factors; determination of the bortezomib dosage for inhibiting the growth of vascular lumen without toxicity for HUVECs | [197] |
| GelMA | HUVECs, HepG2 | Nonalcoholic fatty liver disease | Promotion of vascularization by coculture of nonparenchymal cells and hepatocytes | Optimization for the ratio of HepG2 and HUVECs; the maintenance of steatosis stage for more than a week; lower levels of intracellular lipids using metformin and pioglitazone after 2 d compared with the group without drugs | [177] |
| GelMA, alginate | HUVECs, MDA-MB-231 | Breast tumor model | Elongate actin of HUVECs towards tumor cells compared with the HUVECs alone | Uniquely fabrication of microfiber-laden minispheroids; high cell viabilities of HUVECs and MDA-MB-231 cells | [120] |
| Collagen, gelatin | GMBs, HUVECs | Tumor tissue | Tow perfusable channels with HUVECs lining on the inner channel surface | 3D GBM model in vitro with hollow vascular channels in the chip for long-term culture and drug delivery; decreased metabolic activity of GBM cells in 3D cell spheroids after temozolomide treatment for 21 d; the shrinkage of tumor mass | [195] |
Abbreviations: 2D - two-dimension, 3D - three-dimension, DOX - doxorubicin, ECFC-ECs - human endothelial colony forming cell-derived ECs, GelMA - gelatin methacrylate, GMBs - glioblastoma multiforme cells, HepG2 - human hepatocellular carcinoma cells, HLECs - human lymphatic endothelial cells, HUVECs - human umbilical vein endothelial cells, IC50 - 50% inhibitory concentration, MCF-7 - human breast cancer cells, PEGDA - poly(ethylene glycol) diacrylate, PEGOA - eight-arm poly(ethylene glycol) acrylate, VEGF- vascular endothelial growth factors.