Synthetic cell-based tissues for bottom-up assembly of artificial lymphatic organs

Abstract

Synthetic cells have emerged as novel biomimetic materials for studying fundamental cellular functions and enabling new therapeutic approaches. However, replicating the structure and function of complete tissues as self-organized 3D collectives has remained challenging. Here, we engineer lymph node-mimicking 3D lymphatic bottom-up tissues (lymphBUTs) with mechanical adaptability, metabolic activity, and hierarchical microstructural organization based on individual synthetic cells. We demonstrate that primary human immune cells spontaneously infiltrate and functionally integrate into these synthetic lymph nodes to form living tissue hybrids. By tuning the lymphBUT micro-organization and metabolic activity, we induce the ex vivo expansion of therapeutic CD8+ T cells with an IL-10+/IL-17+ regulatory phenotype. Our study highlights the functional integration of living and non-living matter, advancing synthetic cell engineering toward 3D tissue structures.