Table 2.
Comparison of advantages and disadvantages of scaffold-based models and cardiac spheroids.
| Advantage | Features of cardiac spheroids | Disadvantage |
|---|---|---|
| Uses only a small number of potentially costly cells per data point | Small size of multicellular aggregates | Methods like protein chemistry and RNA extraction need pooling of spheroids |
| No interference of scaffold proteins with the development of the microtissue or the outcome of assays | Made without additional scaffold proteins | Some ECM factors could improve survival and self-organization of the tissue |
| Spheroid is quickly formed and ready for drug treatment and analysis | Assembles spontaneously by gravity or on non-adhesive surface | Little control over the distribution of cell types or overall shape, may result in multiple spheroids |
| Manipulation by pipetting and sedimentation, no touching | Spheroids are floating in culture | Spheroids may get lost or stuck on surfaces in pipetting steps |
| Mimics thicker tissues (and tumors) | Larger spheroids develop zones of o2, PH, metabolites | Reduced viability, variable results, limited diffusion |
| Motion activity and calcium cycling correlates with cell viability and drug treatment | Show long-term spontaneous contractions | No direct force measurement, non-linear cell alignment |
| Miniaturized multi-well formats and compatible with plate readers | Spheroids can be cultured in single wells | - |
| Advantage | Features of scaffold-based models (EHT) | Disadvantage |
| Shape can be tailored for applications (screening, maturation, regen. Medicine) | Shape is determined by the scaffold/hydrogel mold | Uses large number of cells per tissue |
| Hydrogel can be adapted for organotypic functions and pathologies (vascularization, stiffness) | Made with scaffold biomaterial and ECM proteins | Limited diffusion, risk of breaking, unequal distribution of cells, potential interference with assays |
| Sensors can be integrated in microphysiological devices | Tissues attached to support structures | Manual steps necessary, small number of tissues of the same batch of cells |
| Mech. And electrical training, physiological function in disease models, force assessment | Linear alignment of muscle cells | - |
| Technology development toward tissue engineering applications | Training protocols show improved maturation of hiPSC-CM | - |