ATPS-enabled single-step printing of chemically and mechanically on-demand tunable perfusable channels in ejectable constructs

Abstract 3D bioprinting approaches offer highly versatile solutions to replicate living tissue and organ structures. While current bioprinting approaches can generate desired shapes and spatially determined patterns, the material selection for embedded bioprinting has remained limited, as it has relied on the use of viscous, shear-thinning, or liquid-like solid materials to create shape controlled constructs, which could then be modified downstream via multi-step processes. We here explore aqueous two-phase system stabilized 3D bioprinting of low viscous materials in combination with supramolecular complexation to fabricate intricate, perfusable engineered constructs that are both mechanically and chemically tunable in a single-step manner. To this end, we introduce Dex-TAB as a highly versatile backbone, that allows for mechanical and chemical tuning during as well as after printing. To showcase the printability as well as spatial chemical modification and mechanical tunability of this material, ejectability, and local/gradual or bulk functionalized interconnected tube shaped constructs were generated. Subsequently, we demonstrated that these functionalized channels could be printed directly into a syringe containing crosslinkable polymer solution, which upon ejection forms pre-patterned perfusable constructs. In short, we report that ATPS enabled low viscous 3D bioprinting can produce highly functional and even potentially minimally invasive injectable yet functionalized and perfusable constructs, which offers opportunities to advance various biofabrication applications.