Synthetic Cell-Based Tissues for Bottom-Up Assembly of Artificial Lymphatic Organs

This study introduces synthetic cell-based tissues, termed lymphatic bottom-up tissues (lymphBUTs), assembled from engineered synthetic cells to mimic the structure, mechanics, and function of lymphatic organs. The authors demonstrate that these millimeter-scale 3D tissues exhibit tunable stiffness, hierarchical microstructure, and metabolic activity, and can support infiltration, activation, and expansion of primary human T cells. Mechanical confinement and tissue architecture were shown to strongly influence T cell activation dynamics, phenotype, and cytokine secretion compared to conventional 2D and bead-based systems. The work establishes lymphBUTs as a versatile platform for immunotherapy research and bottom-up tissue engineering, integrating mechanical, biochemical, and metabolic cues in a controllable synthetic tissue model.