Microfluidic engineering of immune-competent organs-on-chips and their applications

The emerging field of biomimetic microfluidics is advancing the engineering of immune-competent Organs-on-Chips. These systems overcome the constraints of conventional models by using precise microengineering to regulate cellular composition, three-dimensional extracellular matrix architecture, and dynamic biophysical signals. This review summarizes the core design principles, integrating microfluidics, tissue engineering, and biomaterials, that facilitate the reconstitution of physiological and immune-relevant pathological niches. We examine how such tunable control is utilized to model specific immune contexts, including tumor microenvironments for immunotherapy screening, inflammatory processes in barrier organs, and autoimmune disorders. The integration of these chips with patient-derived organoids and multi-omics technologies is emphasized, illustrating how this combined approach provides new mechanistic insights into human immunology. Finally, we consider the translational prospects of these platforms in promoting personalized immuno-medicine and accelerating immunotherapeutic development, while also addressing ongoing challenges in standardization and the incorporation of greater biological complexity.