ABSTRACT Successfully recapitulating functional tissue‐scale biological structures using additive manufacturing requires simultaneous scaling up to reach clinically relevant sizes and scaling down to incorporate internal vascular‐like features to support high cell viability. This work reports a new multiscale assembly method that integrates cell‐seeded hydrogel modules via gluing to create larger constructs. Scalability is based on an intuitive concept of stacking modules, which allows for a high degree of geometric freedom without the need for specialized equipment. Projection Stereolithography (PSLA) is used to print centimeter‐sized modules using gelatin methacryloyl aminoethyl methacrylate (GelMA‐AEMA). Each module (500 mm 3 ) contains two independent hollow features: seeding port‐arrays to facilitate cell seeding and branched channel networks to enable perfusion. New multi‐material bioreactors are developed, integrating a rigid core with a flexible skin featuring needle septa to yield a watertight seal, providing a sterile environment for perfusion culture. In parallel, a novel gluing strategy is developed, and its efficacy is demonstrated by perfusing dye through an 18‐module assembly. For cell‐seeding experiments, model stromal cells are seeded within a 2‐module assembly, followed by media perfusion. Through assembly of pre‐printed perfusable hydrogel modules, this work helps address key limitations of existing methods and advances development toward realizing large‐scale reproducible tissue constructs.
Geffert et al. (Mon,) studied this question.