High resolution bioprinting of multi-component hydrogels

Materials capable of directing cell fate by providing spatially-graded mechanical and biomolecular cues are critically important in the reconstitution of living matter. Herein, we report a multi-component inkjet bioprinting method that allows for spatially varying composition and network properties in cell-instructive glycosaminoglycan (GAG)-based biohybrid and pure poly(ethylene glycol) hydrogels with unprecedented (50 mu m) resolution. The principle relies on the covalent crosslinking of different polymeric precursors through a very rapid bio-orthogonal Michael type addition scheme adjusted in ways to occur during the fusion ofbio-ink droplets prior to and upon contact with the target. Exemplary data show that chemotactic molecular gradients produced by this approach within printed GAG-gels of defined zonal architecture can effectively direct migratory activity and morphogenesis of embedded human bone-marrow derived mesenchymal stem cells. The introduced methodology is expected to enable a new, holistic level of control over reductionistic tissue and organoid models.