Microphysiological Systems of Lymphatics and Immune Organs

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Microphysiological systems (MPS) that incorporate engineered blood vasculatures have enabled new opportunities to study human physiology and disease, offering platforms for drug development, tissue modeling, and regenerative medicine. However, most human tissues also contain an equally complex yet underrepresented secondary vascular network, the lymphatic system. Lymphatics play indispensable roles in interstitial fluid drainage, immune cell trafficking, and antigen presentation, and are central to the pathophysiology of diseases such as lymphedema, chronic inflammation, and cancer metastasis. Despite their critical biological functions, lymphatic vessels and associated immune structures, such as lymph nodes, remain absent from current in vitro models. Integrating lymphatics into biomaterials-based MPS is essential for capturing the dynamic interplay between fluid transport, immune surveillance, and tissue homeostasis. This review surveys recent progress in engineering lymphatic microenvironments and immune organoids within biomaterials-based MPS, emphasizing innovative strategies to recreate the biochemical and biophysical complexity of native lymphatic tissues. Advances are highlighted in tunable extracellular matrix platforms, humanized cell sourcing, and precision fabrication techniques, including perfusable, modular, and scalable models. The integration of lymphatic compon

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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