Microfluidic Techniques for Next‐Generation Organoid Systems

Abstract Organoids are 3D multicellular structures derived from pluripotent stem cells (PSCs) or adult stem cells (ASCs), which have attracted increasing interest in the fields of drug screening, cell therapy, and regenerative medicine. Despite considerable success in culturing organoids with native microanatomy, challenges to achieving a physiologically relevant microenvironment remain. Complex dynamic feedback between cells and the extracellular matrix and uncontrollable mechano‐physiological cues hamper the further study of organoid systems. Innovative engineering approaches are needed to produce, control, and analyze organoids and their microenvironment. Organoids‐on‐a‐chip, inspired by organs‐on‐a‐chip, presents a major technological breakthrough in providing physiologically relevant environmental parameters. Organoids cultured on a chip recapitulate the anatomical and physiological features of organs during development and disease. In this review, the authors examine how microfluidic approaches integrate biomaterials, microscale technology, and stem cell biology to construct a biomimetic microenvironment that is suitable for building high‐fidelity human organ structures in vitro. Applying engineering techniques in organoids‐on‐a‐chip, such as genome editing and omics analysis, can greatly contribute to a better understanding of molecular pathogenesis. Moreover, the next‐generation organoid culture system may integrate multiple organoids in a single chip device to explore multi‐organoid platforms to fulfill the goal of building 3D organotypic models.