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

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.