User-friendly microfluidic manufacturing of hydrogel microspheres with sharp needle

Abstract Hydrogel microspheres are flexible microstructures with many fascinating functions, such as three-dimensional cell culture, injection therapy, drug delivery, organoids and microtissues construction. The traditional methods of manufacturing hydrogel microspheres more or less have some shortcomings, such as atomization/emulsion method with uneven sizes; piezoelectric-/thermal-/electric-assisted inkjet with high cell damage and unknown cell growth effects; microfluidic manufacturing with sophisticated microdevices etc, which lead to poor user experiences. Here, we designed a user-friendly microfluidic device to generate hydrogel microspheres with sharp needles that can be replaced at will. Specifically, a commercial tapered opening sharp needle was inserted into a transparent silicone tube with the tapered opening facing the upper wall of the silicone tube. Then, gelatin methacrylate (GelMA) solution and paraffin oil were pumped into the sharp needle and the silicone tube respectively. GelMA microdroplets were formed under the shear stress of the silicone tube and the oil phase, and after being photo-crosslinked in situ , GelMA microspheres with uniform and adjustable sizes can be generated. Due to the simplicity of our original device, heterogeneous microspheres such as Janus, core–shell and hollow microspheres can be easily manufactured by simple modification of the device. In addition, we demonstrated the strong flexibility and maneuverability of the microspheres through macroscopic free assembly. Finally, we prepared different cell-laden GelMA microspheres, and the cells showed stretching behavior similar to that in vivo after a short period culture, which indicated the high bioactivity of GelMA microspheres. Meanwhile, we cultured the Janus cell-laden GelMA microspheres and the assembly of cell-laden GelMA microspheres, where the cells stretched and interacted, demonstrating the potential of GelMA microspheres for co-culture and fabrication of large-scale tissue constructs. In view of the above results, our user-friendly microfluidic manufacturing method of hydrogel microspheres with sharp needles will provide great convenience to relevant researchers.