Table 1 Comparison table of different organoid and spheroid production methods
Extracellular Matrix Scaffold | Spinning Bioreactor | Hanging-Drop | Low-adherent Substrates | Magnetic Levitation | Bioprinted | Micropatterning | Microfluidic | |
|---|---|---|---|---|---|---|---|---|
3D Culture Yield | Organoid | Organoid and Spheroid | Spheroid | Spheroid | Spheroid | Organoid | Spheroid | Organoid |
Description | Stem cells are placed in Matrigel (or ECM mix) and maintained in culture | Suspension cultures placed within spinner flasks or bioreactors with high-viscosity reagents | Cells are suspended in media droplet, within droplet cells aggregate at the air–liquid interface | Cell seeded onto low-adherent/hydrophilic substrates to form cell aggregates | Nanoparticles ingested by cells, cells are placed in a low-adherent substrate, and a magnet lid is used to aggregate the cells | Additive manufacture of ECM, cytokines, & cells | Microcontact printing and soft-lithography patterning of ECM | Micron-sized structures to hold 3D culture and incorporation of microsensors |
Challenges | Lack of reproducibility with natural ECM; synthetic ECM requires upregulating reagents | Generates large & heterogenous spheroids; imposes shear forces on cells | Media change is difficult; costly if robotics is involved; droplets <50 µL | Not adaptable to all cell types; heterogenous | Nanoparticles can be toxic and expensive | Selection of bioink with desired characteristics | Poor reproducibility if not automated, lack of patterning efficiency, requires expensive equipment | Low cell recovery can limit post-cell analysis |
Advantage | Reproduces microenvironment; can observe cell adhesion and migration | Vessel size allows for a wide range of model sizes to be generated | Consistent; works with small cell population; no need for ECM; array production | Does not require ECM; cost-effective | Increased growth rates; no requirement of media or ECM | Allows for complex & organized structures; the use of multiple cell types | Allows for structure control; array production | Allows for nutrient delivery; averts necrosis; constricts model size; replicates microenvironment, array production |
Complexity | Moderate | Moderate | Simple | Simple | Simple | Moderate | Moderate | Moderate |
Throughput | Moderate | High | High | High | High | High | High | High |
Cost/organoid batch | $700-80022 | $241 | $2047 | $20052 | $2069 | $1.5017 | $~195 | |
Volume holding organoid/organoids | ~550 µL | 45 mL | <50 µL | 10 mL | 1 mL | 40 µL | 100 µL | 50 µL |
Cell/organ type | Mouse and human prostate; human ovarian, human and mouse hepatocytes; lung cancer22,23,24 | Breast Cancer41 | 3D gastrointestinal model (epithelial and stromal cells)47 | Mesenchymal stem cells52 | Cardiovascular organoids62 |
