Are there any disadvantages for 3D cultures?

3D cultures are generally the preferred technique for studying the normal physiology and biochemistry of cells. However, it does have a few disadvantages.

The major disadvantage of 3D cultures is that they are labor intensive and time consuming. 3D culture requires the separation of individual cells from spheroid structures by proteolytic degradation of single layers. This can take anywhere from several hours to a few days.

In addition, some matrices used in 3D cultures are made from animal origin components which may make implementation for clinical work difficult. Other matrices made from tissue, such as basement membrane extracts, can contain unknown or unwanted components like growth factors or viruses that can skew the studies. Still, other matrices allow for attachment but not efficient removal of the cells, making assay development difficult.