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

Abstract

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.

3D Scaffolds Fabrication via Bicomponent Microgels Assembly: Process Optimization and In Vitro Characterization

“…In the last years, SA-based hydrogels have been widely studied as 3D platforms for different biomedical applications. In particular, alginate beads have been proposed as a good alternative to study cell behavior, providing a suitable platform for anchorage-dependent cells [ 20 ]. However, alginate-based materials have shown some biological drawbacks, due to the lack of adhesive properties that limit the cell recognition [ 21 , 22 ].…”

“…In this case, droplet shape and structure were stabilized by a gelation mechanism triggered by ionotropic interaction in the collecting bath [ 17 , 24 ]. An accurate setting of material parameters including solution properties (e.g., polymer concentration, molecular weight, viscosity) and process conditions (i.e., voltage, flow rate, distance between electrodes, needle diameter) enabled to fabricate microgels with tailored morphological features (i.e., size, shape), and easy to be functionalized by biochemical signals to support cell interactions [ 20 ]. Herein, microgels were also assembled to form hydrogel-like scaffolds with improved features for biological use: interconnected pores generated by adjacent microgels can guide cell ingrowth and tissue formation, while large surface/volume ratio and short diffusion distance can more efficiently support mass transport and nutrients exchange, with a key role on long-term survival of cells [ 25 , 26 ].…”

Electro Fluid Dynamics: A Route to Design Polymers and Composites for Biomedical and Bio-Sustainable Applications

“…The fabrication of alginate microgels loaded with caffeine can be mentioned as a model for low molecular compound encapsulation. In this case, microgels were coated with chitosan to enhance caffeine retention [ 124 ].…”

Mineralized Polyvinyl Alcohol/Sodium Alginate Hydrogels Incorporating Cellulose Nanofibrils for Bone and Wound Healing

“…Recently, the discovery of new formulations involving natural polymers (i.e., proteins and/or polysaccharides) in combination with innovative processing techniques is leading to design composite materials with multiscale functionalities for bone healing/repair processes [ 27 ]. In particular, alginates are a mixture of two monosaccharides, i.e., guluronic and mannuronic acids, which can interact with divalent cations under normal physiological conditions to form cationic gels [ 28 ] and are promising materials to fabricate bioinspired platforms for efficaciously hosting cells and molecular signals [ 29 ]. In this view, a variety of experimental studies have been conducted to promote the mineralization of polysaccharide-like matrices via controlled calcium phosphate deposition [ 30 , 31 , 32 ], also suggesting innovative therapeutic solutions to support healing processes of hard [ 33 ] and soft [ 34 ] tissues.…”