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

Abstract Cell‐lined luminal structures are crucial for nutrient transport, tissue barriers, and paracrine interactions. Modeling these structures is essential for developing accurate in vitro 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 technical complexity. To address these challenges, we have developed an array of 3D tissue constructs with luminal structures that overcome current limitations. The platform employs a sacrificial micromolding technique to generate arrays of luminal structures within extracellular matrix (ECM) 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, the platform presents a promising technology for multi‐organ modeling research and drug discovery applications.