Multiplexed Luminal Tissue Constructs with Reconfigurable Barriers for Dynamic Modeling of Multi‐Tissue Interactions

Cell-lined luminal structures are crucial for nutrient transport, tissue barriers, and paracrine interactions. Modeling these structures is essential for developing accurate <i>in vitro</i> models, but conventional systems struggle with their geometrical complexity. While recent microengineering and self-assembly platforms have shown promise, they face limitations in throughput, equipment compatibility, and operational complexity. To address these challenges, we have developed an array of three-dimensional tissue constructs with luminal structures that overcome current limitations. Our platform employs a sacrificial micromolding technique to generate arrays of luminal structures within extracellular matrix hydrogels in a single process, improving throughput. We also incorporate a reconfigurable oil barrier between tissue compartments, enabling dynamic modeling of multi-tissue interactions. This approach reduces fabrication complexity, increases robustness, and offers high flexibility in arranging multi-tissue constructs. The platform allows formation of multiple luminal structures and tissue configurations, discrete compartmentalization for parallel experiments, and reconfiguration of the oil barrier to study physiological multi-tissue interactions. By facilitating complex microtissue cultures and multi-tissue experiments on a single device, our platform presents a promising technology for multi-organ modeling research and drug discovery applications.