Programming Delayed Dissolution Into Sacrificial Bioinks For Dynamic Temporal Control of Architecture within 3D-Bioprinted Constructs

Abstract

Sacrificial printing allows introduction of architectural cues within engineered tissue constructs. This strategy adopts the use of a 3D-printed sacrificial ink that is embedded within a bulk hydrogel which is subsequently dissolved to leave open-channels. However, current conventional sacrificial inks do not recapitulate the dynamic nature of tissue development, such as the temporal presentation of architectural cues matching cellular requirements during different stages of maturation. To address this limitation, a new class of sacrificial inks is developed that exhibits tailorable and programmable delayed dissolution profiles (1–17 days), by exploiting the unique ability of the ruthenium complex and sodium persulfate initiating system to crosslink native tyrosine groups present in non-chemically modified gelatin. These novel sacrificial inks are also shown to be compatible with a range of biofabrication technologies, including extrusion-based printing, digital-light processing, and volumetric bioprinting. Further embedding these sacrificial templates within cell-laden bulk hydrogels displays precise control over the spatial and temporal introduction of architectural features into cell-laden hydrogel constructs. This approach demonstrates the unique capacity of delaying dissolution of sacrificial inks to modulate cell behavior, improving the deposition of mineralized matrix and capillary-like network formation in osteogenic and vasculogenic culture, respectively.