Electric field assisted microfluidic platform for generation of tailorable porous microbeads as cell carriers for tissue engineering

Injection of cell-laden scaffolds in the form of mesoscopic particles directly to the site of treatment is one of the most promising approaches to tissue regeneration. Here, we present a novel and highly efficient method for preparation of porous microbeads of tailorable dimensions (in the range ~ 300-1500 mm) and with a uniform and fully interconnected internal porous texture. The method starts with generation of a monodisperse oil-in-water emulsion inside a flow-focusing microfluidic device. This emulsion is later broken-up, with the use of electric field, into mesoscopic double droplets, that in turn serve as a template for the porous microbeads. By tuning the amplitude and frequency of the electric pulses, we precisely produce the template droplets and the resulting porous bead scaffolds. Furthermore, we propose a model of pulsed electro-dripping that predicts the size of the template droplets as a function of the applied voltage. To prove the potential of the porous microbeads as cell carries, we test them with human mesenchymal stem cells (hMSCs) and hepatic cells (HepaRG), monitoring their viability and degree of microbead colonization. Finally, we benchmark the presented porous microbeads against conventional microparticles with non-homogenous internal texture, revealing their superior performance.