Table 1.
Generation Methods | Advantages | Disadvantages | References | ||
---|---|---|---|---|---|
Traditional generation methods | Non-adhesive surface liquid covering (the microwell arrays method) | Easy to operate Low sheer stresses High yield Low cost |
Labor intensive Variation in MCSs size and shape Inability to stimulate cell-ECM interactions |
[7,21,22,23,24,25,26,27,28] | |
Hanging drop | Easy to operate Good size control Low sheer stresses Co-cultivation of multiple cells |
Labor intensive Low yield Difficulties in mass production Difficult to change the medium Difficult to transfer the spheroid |
[29,30,31,32] | ||
Rotating flask | Mass generation Easy to operate Long-term culture Dynamic microenvironment Co-cultivation of multiple cells |
High sheer stresses Variation in MCSs size and shape Inconvenient to observe the generation process of the spheroid Inability to stimulate cell-ECM interactions |
[33] | ||
External force | Rapid generation Good size control Co-cultivation of multiple cells |
Requiring professional equipment The potential impact of external forces on cells is unknown |
[10,34,35,36,37,38,39] | ||
Biomaterials (scaffolds) and microfluidic technology | Hydrogel (scaffold, cell sheets) | Natural polymers | Realistic microenvironment High yield Good size control Low sheer stresses Labor saving Aggregates of different shapes can be generated Co-cultivation of multiple cells |
Requiring professional equipment Higher requirements for operation Higher cost |
[40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74] |
Synthetic polymers | [75,76,77,78,79,80,81,82,83,84,85] | ||||
Microfluidic | Emulsion technology | Realistic microenvironment High yield Long-term culture Good size control Low sheer stresses High-throughput analysis Labor saving Dynamic microenvironment Generate aggregates of different shapes Co-cultivation of multiple cells Low reagent consumptionLow cell usage |
Requiring professional equipment Higher requirements for operation Higher cost |
[3,86,87,88,89,90,91,92,93] | |
Microwell and U-shaped microfluidic system | [6,12,23,94,95,96,97,98,99,100] |