Fabrication of Cell Spheroids for 3D Cell Culture and Biomedical Applications

The significance of 3D cell culture—i.e., the maintenance of cell characteristics by mimicking the natural environment—has been increasing, and various 3D cell culture methods have been proposed. 3D cell culture is a widely used cell spheroid culture method, which is a representative method of matrix-free 3D cell culture. In contrast with that in conventional 2D cell culture, cells aggregate in a spherical shape with abundant cell–cell and cell–matrix interactions that more closely resemble the in vivo environment in a 3D culture. In a cell spheroid culture, the viability and functionality of spheroids change based on the cell type and morphology, and their controllable characteristics differ depending on the fabrication method used. Moreover, the mass production and size controllability of spheroids are dependent on the fabrication method used; therefore, the spheroid utilization method is also different. In this review, representative cell spheroid fabrication methods are examined, and the possibility of standardization is discussed so that these methods can be widely used. In addition, the biomedical applications of spheroids and their potential for future development are explored.