Engineered Microsystems for Spheroid and Organoid Studies

3D in vitro model systems such as spheroids and organoids provide an opportunity to extend the physiological understanding using recapitulated tissues that mimic physiological characteristics of in vivo microenvironments. Unlike 2D systems, 3D in vitro systems can bridge the gap between inadequate 2D cultures and the in vivo environments, providing novel insights on complex physiological mechanisms at various scales of organization, ranging from the cellular, tissue‐, to organ‐levels. To satisfy the ever‐increasing need for highly complex and sophisticated systems, many 3D in vitro models with advanced microengineering techniques have been developed to answer diverse physiological questions. This review summarizes recent advances in engineered microsystems for the development of 3D in vitro model systems. The relationship between the underlying physics behind the microengineering techniques, and their ability to recapitulate distinct 3D cellular structures and functions of diverse types of tissues and organs are highlighted and discussed in detail. A number of 3D in vitro models and their engineering principles are also introduced. Finally, current limitations are summarized, and perspectives for future directions in guiding the development of 3D in vitro model systems using microengineering techniques are provided. 3D in vitro models including spheroids and organoids provide an opportunity to extend the physiological understanding of in vivo microenvironments. In this review, engineered microsystems are categorized into four types: microwell‐, centrifugation‐, liquid drop‐, and microchannel‐based culture systems. The five mechanical principles that can uniquely influence the formation of 3D cellular structures are also recapitulated.