Electro‐Assisted Bioprinting of Low‐Concentration GelMA Microdroplets

Abstract

Low‐concentration gelatin methacryloyl (GelMA) has excellent biocompatibility to cell‐laden structures. However, it is still a big challenge to stably fabricate organoids (even microdroplets) using this material due to its extremely low viscosity. Here, a promising electro‐assisted bioprinting method is developed, which can print low‐concentration pure GelMA microdroplets with low cost, low cell damage, and high efficiency. With the help of electrostatic attraction, uniform GelMA microdroplets measuring about 100 μm are rapidly printed. Due to the application of lower external forces to separate the droplets, cell damage during printing is negligible, which often happens in piezoelectric or thermal inkjet bioprinting. Different printing states and effects of printing parameters (voltages, gas pressure, nozzle size, etc.) on microdroplet diameter are also investigated. The fundamental properties of low‐concentration GelMA microspheres are subsequently studied. The results show that the printed microspheres with 5% w/v GelMA can provide a suitable microenvironment for laden bone marrow stem cells. Finally, it is demonstrated that the printed microdroplets can be used in building microspheroidal organoids, in drug controlled release, and in 3D bioprinting as biobricks. This method shows great potential use in cell therapy, drug delivery, and organoid building.

Multiparametric Analysis of Tissue Spheroids Fabricated from Different Types of Cells

“…[ 25,26 ] Different methods for spheroids’ generation have been established which are used depending on their prospective utilization. The main examples include hanging drop method, [ 27,28 ] spinner flask culture, [ 29 ] pellet culture, [ 30 ] rotating wall vessel, [ 31 ] liquid overlay method, [ 32 ] micro‐molded non‐adhesive hydrogel technology, [ 33,34 ] production of spheroids in non‐adhesive microplates, [ 35 ] cell's encapsulation in different hydrogels, [ 36–38 ] TS fabrication applying non‐adhesive hydrogel microarrays, [ 39 ] TS generation applying polymeric aqueous two‐phase system. [ 40–42 ] Modern techniques for TS production use external forces such as acoustic, [ 43 ] magnetic, [ 10,44,45 ] and electric fields to guide cell aggregation.…”

A Perspective on Using Machine Learning in 3D Bioprinting

“…In 3D bioprinting, similarly, machine learning can be used for improving the fabrication process, such as predicting process conditions and optimizing process parameters. Taking extrusion-based bioprinting as an example, it is now able to stably fabricate organoids using low-concentration gelatin-methacryloyl with the help of electrostatic attraction[ 37 ]. However, what are the best values of these parameters?…”

Why choose 3D bioprinting? Part II: methods and bioprinters

“…Because it avoids excessive pressure during extrusion process of bioink through nozzle, which would affect cell viability, EHDJ is suitable for bioprinting bioinks with high weight/volume ratio and high cell concentration. This bioprinting method has advantages such as low cost, high efficiency, high precision, deposition position controllability and low cell damage, but it also has limitations such as electric accumulation affecting deformation of complex constructions; electric field intensity is related to the height of printed structure, leading to complicated process control and difficult to stack many layers [8].…”