Cell encapsulation in core-shell microcapsules through coaxial electrospinning system and horseradish peroxidase-catalyzed crosslinking

Cellular growth of enclosed cells in core–shell microcapsules is a key element for the practical use of the device in tissue engineering and biopharmaceutical fields. We developed alginate derivative microcapsules with a liquid core template by horseradish peroxidase crosslinking using an integrated coaxial microfluidic device by electrospray system. The cells and gelatin solution were extruded from the inner channel of coaxial microfluidic device and alginate possessing phenolic moieties (Alg-Ph) and horseradish peroxidase (HRP) flowed from the outer channel. In open electric filed, concentric drops of the two coaxial fluids broken up into microdrops and sprayed into the gelling bath containing hydrogen peroxide to instantly gel alginate in the shell fluid before the two fluids got mixed or gelatin dispersed in a gelling bath. The core–shell structure of about 350 μm in diameter and gel membrane of 42 μm was developed by optimization of operational parameters including electrical voltage, flow rate and concentration of polymers. The physical properties of microcapsules including swelling and mechanical resistance proved the applicability of fabricated vehicles for cell culture systems in vitro and in vivo. The viability of enclosed fibroblast cells in generated core–shell microcapsule was more than 90% which is sufficiently high compared with it before encapsulation. The growth profile and behavior of cells in microcapsules showed appropriate cell growth and the possibility of fabrication of spherical tissue was confirmed through degradation of hydrogel membrane. These results validate the significant potential of coaxial electrospray system and HRP-mediated hydrogelation in the fabrication of cell-laden core–shell microcapsule for tissue engineering and regenerative medicine.