This chapter will provide an overview on scaffold-free 3D models focusing on aggregates, spheroids, and organoids. While often used synonymously, the differences are presented as well as the origin and advancement until the current date. Moreover, the advantages that scaffold-free systems offer and their limitations are discussed as well as fields of applications ranging from stem cell expansion, pharmacological high-throughput tumor drug screening for personalized medicine, to human-on-a-chip systems facilitating the systemic investigation of drug metabolization reducing animal experiments by considering multiple organ functions within one setup. Furthermore, approaches and requirements for the generation and cultivation strategies are outlined.
