Design of alginate based micro-gels via electro fluid dynamics to construct microphysiological cell culture systems

In the last decade, different technological approaches have been proposed for the fabrication of micro-gels as cell carriers to investigate in vitro response. Among them, electro fluid dynamic atomization (EFDAs) is emerging as a highly versatile process that allows atomizing polymer solutions at the micrometric size scale by the application of high voltage electric field. Here, we propose to revisit the process configuration to optimize the fabrication of sodium alginate micro-gels with different physical and mechanical properties and validate their use for in vitro culture with human mesenchymal stem cells (hMSCs). By optical microscopy, we explored the strict correlation between particle morphology and process parameters, that is, voltage, flow rate, electrode gap and needle diameter. Meanwhile, by scanning electron microscopy and atomic force microscopy, we investigated basic differences in terms of physical (i.e., swelling) and mechanical properties (i.e., stiffness), ascribable to alginates solutions with different concentrations. Lastly, in vitro tests confirmed the effect of physical properties of microgels on the biological response of hMSCs cultured onto the surface. In perspective, the integration of alginate with peculiar extracellular matrix (ECM) components (i.e., proteins, mineral phase) may contribute to assign specific biological functionalities to the microgels in order to reproduce 3D models to investigate in vivo-like behavior of cells.