Accessible Biofabrication of Anatomically Inspired Hollow and Branched Hydrogel Constructs by Soft Templating (Sof-T)

Biofabrication has significant potential to advance medicine and research by creating complex and anatomically accurate engineered tissues for implantation or in vitro modeling. However, a persisting challenge of the current biofabrication methods, such as hydrogel-based bioprinting, is to find an efficient, affordable, and reproducible method for the generation of hollow and branched geometries. This is critical for the recapitulation of anatomically realistic structures representative of cardiovascular, respiratory, and other organ systems. Existing bioprinting approaches require complex, multi-step processes and expensive specialized equipment, limiting accessibility and extending fabrication time. Here, we present an alternative 'sacrificial' method for the rapid and accessible creation of hollow and/or branched hydrogel constructs, which we term 'soft templating' (Sof-T). Sof-T utilizes ionic diffusion from a 3D-printed water-soluble polymer to crosslink surface-adsorbed hydrogels followed by the dissolution of the polymer, thus leaving behind the anatomically patterned hydrogels. Using this technique, we readily generated: (1) vascular-like bifurcated aortic conduits, with or without aneurysmal deformities; (2) upper and lower (branched) trachea models; and scale-reduced (3) human hearts and (4) bladders. Overall, Sof-T offers a simple, rapid, and cost-effective strategy for fabricating relatively complex, hollow hydrogel architectures, broadening the access to anatomically relevant constructs for biomedical research and translational and/or educational applications.