Table 1.

Main advantages and disadvantages of the main pre-clinical tissue models.

Pre-Clinical Model	Main Advantages	Main Disadvantages
2D cell cultures	Simple to use	Limited or altered cell–cell and cell–extracellular matrix (ECM) interactions
	Cheap	Altered cell morphology, proliferation, and differentiation
	Standard	Overestimated drugs response
		Lack of metabolic gradients
		Oversimplified
Animal models	High complexity	Time-consuming, laborious, expensive
		Species-specific responses
		Ethical issues
3D cellular spheroids	Cheap	Lack of surrounding ECM
	Metabolic gradients	Susceptibility to physical deterioration
	Proper cell–cell interactions
	In vivo-like cell morphology and proliferation
3D hydrogel-based tissue models	Surrounding ECM with tunable properties	Batch-to-batch variability
	Reproduction of key mechanical and biochemical features of human tissues	Difficult to monitor cell activity with traditional tools
	Proper cell–cell and cell–ECM interactions