Table 2.
Engineering techniques for stem cell spheroid formation.
| Formation method | Culture platform | Platform materials | Structure | Features | Stem cell(Derived species) | Ref. |
|---|---|---|---|---|---|---|
| Hanging drop | Lid of a Petri dish | PolystyreneSolution coating | Square wettable surface | Superhydrophobic patternwith wettable regions | Adipose-derived stem cells(human) | [126] |
| Automated microfluidic device | Water white glass substrates | Through-hole and well | 2.4-mm wells | BMSCs (mouse) | [127] | |
| Pressure-assisted network for droplet accumulation system | Polycarbonatesheet, polyethylene terephthalate | Through-hole well plate | Balanced control of the internal and surrounding pressure | MSCs | [128] | |
| Bio-inspired superhydrophobic substrate | Silicon (Si) | Vertically aligned nanowires | Length: 25 μm | ADSCs (Human) | [17] | |
| Cell printer | – | – | 2 nL or fewer than five cells | ESCs | [129] | |
| Hydrogel scaffold | Sponge-like hydrogel | Gellan gum, silk fibroin | Micropore structures | Porosity: 90 ± 0.7% Pore wall thickness: 6.6 μm | ADSCs (human) | [150] |
| Sandpaper-embossed microstructure | Tetronic-tyramine | Microstructure | Surface roughness from 100 to 200 μm | ADSCs (human) | [148] | |
| Porous microstructure | Poly(l-glutamic acid), polyethylene glycol | Porous microstructure | Pore size: 275–375 μm | ADSCs (human) | [149] | |
| 3D bioprinted matrix | Chitosan methacrylate and polyvinyl alcohol hybrid microparticle ink | Biomimetic microstructures | Scaffold pore size: 250 μm Particle size: 197 μm | BMSCs (rat) | [147] | |
| Microwells | Microstructure | Tet-TA polymer | lotus seedpod-inspired microwell | 200 or 400 μm in width with various depths | ADSCs (human) | [133] |
| Microstructure | Alginate | Hexagonal well array | 100-, 200-, and 400-μm wells | MSCs (mouse) | [134] | |
| Microstructure | PEG hydrogel | Inverted-pyramidal opening well | Diameter: 200 μm | MSCs (human) | [135] | |
| Microstructure | Agarose | Round-bottom microwells | Diameter: 2 mm | iPSCs (human) | [132] | |
| ESCs (human) | ||||||
| Microstructure | Collagen, Matrigel | Micro-honeycomb structures | 100- and 300-μm holes | ESCs (mouse) | [20] | |
| Spiner and rotational methods | Multi-trap acoustic levitation | PDMS, ultrasonic transducer | Cylindrical cavity | Diameter: 5 mm | ADSCs (human) | [139] |
| Height: 10 mm | ||||||
| Pellet culture with nanofiber | Poly(l-lactic acid) (PLLA) | Mineralized fragmented nanofiber | Diameter: 1–2.5 μm | ADSCs (human) | [247] | |
| Length: 60 μm | ||||||
| Pellet culture with nanofiber | Poly(l-lactic acid) (PLLA) | Fragmented nanofiber | Diameter: 400–800 nm | MSCs (human) | [248] | |
| Length: 50–100 μm | ||||||
| Pellet culture with nanofiber | Poly(l-lactic acid) (PLLA), platelet-derived growth | Fragmented nanofiber | Diameter: 5.4 μm | ADSCs (human) | [249] | |
| factor (PDGF), bio-mineral | Length: 100–150 μm | |||||
| Microfluidics | Hydrogel encapsulation | Poly(vinyl alcohol) (PVA) | Microcapsule | Smaller than 200 μm | BMSCs (human) | [162] |
| Droplet-microfluidic platform, micro anchors hole | Agarose | Encapsulation | Diameter: 680 μm | MSCs (human) | [18] | |
| Magnetic field | Magnetic nanoparticles | Iron oxide core (Fe3O4) coated in polydimethylamine | Nanoparticle | Diameter: 200 nm | BMSCs (human) | [15] |
| Magnetic nanoparticles | Iron salts | Nanoparticle | Diameter: 8 nm | ESCs (mouse) | [19] | |
| Magnetic nanoparticles | Gold and iron oxide nanoparticles crosslinked by poly-l-lysine | Nanoparticle | Size: 50 nm | Neural crest-derived mesenchymal stem cells (human) DPSCs (human) | [157] |