This is a photograph of a 3D hydrogel construct obtained through drop-on-drop multi-material bioprinting. Source: Osaka UniversityThis is a photograph of a 3D hydrogel construct obtained through drop-on-drop multi-material bioprinting. Source: Osaka University

Printed replacement human body parts might seem like science fiction, but with the rapid development of technology, it is actually closer to reality than you think. Three-dimensional printed replacement body parts could greatly contribute to regenerative medicine.

“Bioprinting” is still facing many technical challenges. Processing bio-ink and making it stick to itself and hold the desired printed gel structure has been difficult to achieve, especially in inkjet printing. There are a few methods that currently exist for gluing bio-ink droplets together and they don’t work for every cell, which is motivating new alternative approaches.

Building on previous work, Osaka University researchers have refined an enzyme-driven approach to sticking biological structures to be printed.

Shinji Sakai, lead author of the paper, says, ”Printing any kind of tissue structure is a complex process. The bio-ink must have low enough viscosity to flow through the inkjet printer, but also needs to rapidly form a high viscose gel-like structure when printed. Our new approach meets these requirements while avoiding sodium alginate. In fact, the polymer we used offers excellent potential for tailoring the scaffold material for specific purposes."

Currently, sodium alginate is the main gelling agent being used for inkjet bioprinting, but it does have some compatibility problems with certain cell types. The researchers’ new approach is based on hydrogenation mediated by an enzyme, horseradish peroxidase, which can create cross-links between phenyl groups of an added polymer in the presence of the oxidant hydrogen peroxide.

Even though hydrogen peroxide can damage cells, the researchers have carefully tuned the delivery of cells and hydrogen peroxide in separate droplets in order to limit their contact and keep the cells alive. More than 90 percent of the cells were viable in biological test gels prepared in this way. A number of complex test structures could be grown from different types of cells.

"Advances in induced pluripotent stem cell technologies have made it possible for us to induce stem cells to differentiate in many different ways," co-author Makoto Nakamura says. "Now we need new scaffolds so we can print and support these cells to move closer to achieving full 3D printing of functional tissues. Our new approach is highly versatile and should help all groups working to this goal."

The paper on this research was published in Macromolecular Rapid Communications.