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. 2022 Apr 4;19:50–74. doi: 10.1016/j.bioactmat.2022.03.039

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]