Cell spheroids as a versatile research platform: formation mechanisms, high throughput production, characterization
Monize Caiado Decarli1,2, Robson Amaral3, Diogo Peres Dos Santos4
1Department of Engineering of Materials and of Bioprocesses, School of Chemical Engineering, University of Campinas, Av. Albert Einstein, 500, 13083-852 Campinas, SP, Brazil.
Biofabrication
|February 16, 2021
Summary
Three-dimensional (3D) cell culture using spheroids offers a powerful in vitro model for studying tissues and tumors. This review details engineering methods for uniform spheroid generation and highlights applications in drug screening and tissue engineering.
Area of Science:
- Biotechnology
- Tissue Engineering
- Cell Biology
Background:
- Three-dimensional (3D) cell culture closely mimics in vivo tissue and tumor microenvironments.
- Spheroids are attractive 3D models for reproducible cell structures and tissue engineering.
Purpose of the Study:
- To review engineering processes for obtaining uniform 3D cell spheroids.
- To compare dynamic and static culture methods, considering mass transfer and shear stress.
- To discuss computational modeling and characterization techniques for spheroid systems.
Main Methods:
- Focus on non-cell-adhesive hydrogel-based methods and dynamic bioreactor cultures.
- Comparison of dynamic versus static culture techniques.
- Review of spheroid characterization methods.
Main Results:
- Engineering approaches enable uniform 3D cell spheroid production.
- Identified bottlenecks in morphological analysis, cell quantification, viability, gene expression, and metabolic behavior.
- Detailed examination of various spheroid characterization techniques.
Conclusions:
- 3D cell spheroids are versatile tools for in vitro studies.
- Applications span drug screening, pathology development, tissue engineering, biofabrication, and high-throughput platforms.


