Researchers Develop Microfluidic Technique for 3D Printing Living Cells for Tissue Engineering

There are multiple different applications for 3D bioprinting, and many researchers are hard at work to achieve the successful 3D printing of living cells. Now, scientists at the University of Twente (UT) in the Netherlands have developed a new technique that allows for the 3D printing of structures with living cells. The technique, which the scientists call in-air microfluidics (IAMF), is flexible and fast, allowing for viable micro building blocks to be produced, then used to repair damaged tissue.

Microfluidic devices are used to manipulate tiny drops of fluid, and when I say tiny, I mean it – the sizes of the drops are between a micrometer and a millimeter. Typically, chips with small fluidic channels and reactors are used for lab-on-a-chip systems, and while the chips are certainly valuable, thanks in large part to the fact that the droplets can physically carry other substances, the speed at which they leave the chip is too slow. As they typically exit around one microliter per minute, it would take about 17 hours to fill up just one cubic centimeter.

UT researchers wondered if the speed could be increased by manipulating the fluids in the air, instead of in the micro channels. The answer, it turns out, was yes, and their new chip-free technique can be used to fill a cubic centimeter in just a few minutes. The team recently published a paper, titled “In-air microfluidics enables rapid fabrication of emulsion, suspension and 3D modular (bio)materials,” in the Science Advances journal that details their technique; co-authors include Claas Willem Visser of UT’s Physics of Fluids group, Tom Kamperman with the Developmental BioEngineering group, Lisanne P. Karbaat, Detlef Lohse, and Marcel Karperien.

Both Kamperman and Visser are involved in the new IamFluidics spin-off, in which the IAMF technique is used to create functional materials and particles.

One-step additive manufacturing and injection molding of 3D multiscale modular (bio)materials.

The abstract reads, “Microfluidic chips provide unparalleled control over droplets and jets, which have advanced all natural sciences. However, microfluidic applications could be vastly expanded by increasing the per-channel throughput and directly exploiting the output of chips for rapid additive manufacturing. We unlock these features with in-air microfluidics, a new chip-free platform to manipulate microscale liquid streams in the air. By controlling the composition and in-air impact of liquid microjets by surface tension–driven encapsulation, we fabricate monodisperse emulsions, particles, and fibers with diameters of 20 to 300 μm at rates that are 10 to 100 times higher than chip-based droplet microfluidics. Furthermore, in-air microfluidics uniquely enables module-based production of three-dimensional (3D) multiscale (bio)materials in one step because droplets are partially solidified in-flight and can immediately be printed onto a substrate. In-air microfluidics is cytocompatible, as demonstrated by additive manufacturing of 3D modular constructs with tailored microenvironments for multiple cell types. Its in-line control, high throughput and resolution, and cytocompatibility make in-air microfluidics a versatile platform technology for science, industry, and health care.”

IAMF: (A) Chip-based microfluidics enable in-line control over droplets and particles. A chip design where droplets (blue) are transported by a coflow (pink) is shown. (B) IAMF maintains in-line control of chip-based microfluidics but relies on jet ejection and coalescence into air. So a wide range of droplets and particles can be produced at higher flow rates than with chip-based microfluidics.

The researchers used two jets of fluid to capture living cells inside 3D printable material: from the first jet, droplets are then shot at the second jet. It was not difficult to create the jets, which were ejected from fused silica tubing, and they are able to move up to 100 to 1,000 times faster than droplets moving from a microchip’s fluidic channel. In addition, by using jets that contain different types of reactionary fluids, the collision of the droplets can create new materials.

The paper states, “IAMF also omits the need for cleanroom-based chip fabrication and channel wall surface treatments, prevents solidification-induced clogging, and allows oil-free manufacturing of microparticles (for example, microgels). These characteristics facilitate the application of microfluidic technologies in environments that are not readily compatible with microfluidic chips.”

IAMF uses direct deposition of in-air formed capsules or particles onto a substrate, therefore 3D printing multi-scale modular biomaterials in just one step.

These “bio building blocks” are printed in a 3D structure that resembles a sponge, and the internal structure of the biomaterials is not dissimilar to the structure of natural tissue. In addition, while many 3D printing techniques use UV light or heat, which would cause damage to living cells, the researchers’ IAMF technique uses neither. That makes it a promising method for tissue engineering.

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