Shaping soft hydrogels into 3D, multiscale, perfusable models using multimodal printing

Abstract Despite technological advances, the fabrication of multiscale, multi-material, and topologically complex 3D structures using soft hydrogel biomaterials remains a challenge due to the inherent trade-offs between print size/resolution, biomaterial properties, and design complexity. In this work, we combine additive (macroscale) digital light projection (DLP) mode with subtractive (microscale) two-photon ablation (TPA) mode with multi-material exchange capability. We identify ideal hydrogel formulations that are compatible with both DLP and TPA modes of processing. Technical challenges related to multimodal fabrication such as alignment of multiscale topologies to facilitate seamless media perfusion, soft–hard multi-material printing to facilitate handling of mechanically weak hydrogel constructs, and hydrogel swelling during printing, were resolved. To highlight the novelty of this hybrid platform, we fabricated centimeter-scale hydrogel constructs with embedded microscale perfusable topologies that cannot be achieved by isolated use of either DLP or TPA modes. This includes simpler microfluidic chips with independently perfusable microchannels to more complex 3D constructs with embedded, multiscale fluidic circuits that mimic the alveoli-capillary interface, or microfluidic chips with endothelialized microchannels. The unique ability of this multimodal platform to mimic in vivo -like multiscale complexities is the first step towards the development of next-generation organ-on-chips.