3D Printed Solid‐Walled Zein Vascular Network With Long‐Term Perfusion Stability and Trans‐Wall Transport

ABSTRACT As in vitro tissue models, including organoids, become thicker and more complex, diffusion‐limited three‐dimensional (3D) culture increasingly fails to sustain long‐term viability, nutrient supply, and spatial microenvironmental regulation. Existing vascularization, perfusion, and chip‐based strategies still struggle to integrate complex 3D architecture, durable perfusion, mechanical integrity, and controlled trans‐wall exchange in thick constructs. Here, a fibril‐reinforced, 3D‐printed solid‐walled zein vascular interface is developed to couple long‐term perfusion stability with wall‐mediated mass transport. Homologous zein fibrils enable direct printing of branched perfusable conduits with tunable porous walls, avoiding sacrificial hollow‐channel templating while improving deformation resistance and preserving permeability during 30 days of continuous perfusion. Wall architecture establishes two application‐specific transport regimes. In a regulated‐exchange regime, the interface supports nutrient delivery in 33 × 21 × 11 mm cell‐laden constructs, maintaining long‐term survival and enhancing CD31 expression within a continuously perfused peri‐conduit microenvironment. In a high‐permeability regime, enlarged porous walls generate spatial transport gradients, distance‐dependent heterogeneity, and enhanced permeability and retention (EPR)‐relevant trans‐wall nanocarrier transport with peri‐conduit accumulation, enabling evaluation of photoresponsive liposomal delivery and polyaniline‐mediated photothermal responses. This zein platform integrates printable biomaterial architecture, perfusion durability, and tunable wall‐mediated transport for thick tissue support and EPR‐relevant therapeutic evaluation in advanced in vitro model systems.