Dear colleague,
Spheroids, as 3D cell aggregates, form naturally in low and ultra-low attachment surfaces. The purpose of their use is to "simulate" the physical structure and interactions of cells within tissues. An important characteristic of spheroids is the diverse layering of cells that occurs inside the spheroids due to the difference in bioavailability of oxygen and nutrients. Thus, in my opinion it is important to retain the structure of the natural forming spheroids (for example in some cases cancer cell spheroids contain a necrotic/hypoxic core/center).
However there are some applications that integrate both scaffolding technologies and cell spheroids but retain the structure of the spheroids (i have not used them so I don't know the details). Some of these applications utilize 3D scaffolds to control the size of the spheroids while others use scaffolds to enhance the microenvironment characteristics of their model.
The following article summarizes both Scaffold-free applications and Scaffolded Spheroid Applications:
Article The utility of biomedical scaffolds laden with spheroids in ...
Finally, there is also the application of cell-laden polymeric microspheres but that model does not involve spheroids.
Although I could not get into details I hope that was helpful.
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