Integrated applications of microfluidics, organoids, and 3D bioprinting in in vitro 3D biomimetic models

Biomedical research has long faced challenges in accurately replicating human organ microenvironments and overcoming interspecies biological differences, thereby limiting the in-depth understanding of physiopathological mechanisms and hindering the development of cutting-edge therapeutic approaches. Recently, novel technologies such as organoids, microfluidics, and three-dimensional (3D) bioprinting offer promising solutions, fostering innovation, and accelerating progress in biomedical science. However, none of these technologies alone can serve as a fully representative preclinical model, underscoring the need for integrated approaches. This review provides a comprehensive overview of various strategies combining microfluidics, organoids, and 3D bioprinting to develop more physiologically relevant preclinical models. After briefly introducing each technology, we examine the advantages of their pairwise integrations and discuss their prospects for drug research, disease modeling, and beyond. In addition, we explore the potential of combining all three technologies, including the emerging concept of 4D culture systems, which incorporate the temporal dimension to better mimic dynamic biological processes. We anticipate that these integrated models will propel significant advances in biomedical research and contribute to the transformation of future healthcare.

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