ABSTRACT The fabrication of native tissue‐like structures with gradual transitions in material properties, cell types, and growth factors remains a major challenge in biofabrication due to the lack of suitable methods. Mimicking the hierarchical organization of living tissues is essential for functional models, yet creating gradient, multimaterial architectures that ensure high cell viability and proper tissue maturation remains difficult. Here, we present a novel approach combining extrusion‐based 3D bioprinting with static mixing, using self‐designed digital light processing (DLP) printed mixing units to fabricate defined gradient structures. Two passive mixing geometries, sinusoidal and obstacle‐based, are designed and benchmarked against commercially available static mixers. A method for the evaluation of mixing performance is developed using dyed alginate solutions extruded with cavity pumps. The obstacle design achieved superior mixing compared to the sinusoidal and commercial counterparts. Biocompatibility is assessed with U87 and NIH3T3 cells extruded in polymer solutions of varying viscosities (gelAGE, PEG‐2‐SH, and Matrigel), demonstrating significantly enhanced cell viability in the self‐designed mixers. Graded constructs are produced and characterized via nanoindentation, confirming continuous stiffness gradients. Overall, this approach enables fabrication of gradient structures with enhanced mixing and cell viability, providing a robust, adaptable platform for advanced biofabrication.
Hofmann et al. (Mon,) studied this question.