• biofabrication
• core - shell spheroid
• in-vitro model

BIOFABRICATION OF CORE-SHELL SPHEROIDS FOR ENGINEERING BIOLOGICAL STRUCTURES IN-VITRO
Physiologically relevant in vitro models need to reproduce both structural and dynamic features of in-vivo tissues. However, to date, the replication of physiological deformation mechanisms and their combination with a 3D structure is still a challenge. For this reason, we developed a new technique for the fabrication of core-shell spheroids which, in combination with magneto-responsive gels, are able to replicate the architecture and motility of the alveolar and intestinal barrier. A COre-Shell Microbead Creator (COSMIC) was re-engineered to enable the encapsulation of cells in the core-shell beads. The system is based on commercial coaxial needles actuated by stepper motors and controlled by a user-friendly interface. Air-, liquid- and solid-core shell structures were generated thanks to drop formation and alginate crosslinking in a 0.1 M calcium chloride (CaCl2) solution, and characterised. Magneto-responsive gels were prepared using agarose and magnetite nanoparticles at different concentrations, demonstrating their suitability for the replication of physiological strain levels. Finally, preliminary cell tests were performed using Caco-2 cells showing the biocompatibility of the encapsulation technique. Therefore, this strategy represents a step forward towards the definition of physiologically relevant in vitro models, which can also be seen as alternatives to animal testing in line with the 3R principles.