Engineered Microsystems for Spheroid and Organoid Studies

Three-dimensional (3D) in vitro model systems such as spheroids and organoids provide an opportunity to extend our physiological understanding using recapitulated tissues that mimic physiological characteristics of in vivo microenvironments. Unlike two-dimensional (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. We highlight and discuss in detail 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. We also introduce a number of 3D in vitro models and their engineering principles. Finally, we summarize current limitations, and provide perspectives for future directions in guiding the development of 3D in vitro model systems using microengineering techniques.