A microscope image of the novel micro-scaffold. Image: TU Wien.
A microscope image of the novel micro-scaffold. Image: TU Wien.

If bodily tissue could be produced artificially from stem cells, then injuries could be healed with the body's own cells, and one day it may even be possible to produce artificial organs. But getting cells into the desired shape is difficult. Existing methods involve either creating small tissue building blocks, such as round cell agglomerates or flat cell sheets, and then assembling them into the desired shape, or creating a fine, porous scaffold with the desired shape that is cultivated with cells. Both approaches have advantages and disadvantages.

Researchers at the Vienna University of Technology (TU Wien) in Austria have now developed a third approach. Using a special laser-based 3D printing technique, they have produced micro-scaffolds with a diameter of less than a third of a millimetre, which can accommodate thousands of cells. This approach combines an initial high cell density with the flexibility to adapt to the shape and mechanical properties of the scaffold.

"The scaffold-based approaches that have been developed so far have great advantages: if you first make a porous scaffold, you can precisely define its mechanical properties," says Olivier Guillaume, a researcher in the team of Aleksandr Ovsianikov at TU Wien’s Institute of Materials Science and Technology and lead author of a paper on this work in Acta Biomaterialia. "The scaffold can be soft or hard as needed, it consists of biocompatible materials that are degraded in the body. They can even be equipped with special biomolecules that promote tissue formation."

The downside, however, is that it is difficult to populate such a scaffold with cells quickly and completely. Especially with large scaffolds, it takes a long time for the cells to migrate into the interior of the structure, meaning the cell density remains very low and inhomogeneous.

The situation is completely different if no such scaffold is used. In that case, it is possible to simply grow small cell agglomerates, which are then joined together in the desired shape so that they eventually merge. With this technique, the number of cells is large from the start, but there are hardly any possibilities to intervene in the process. For example, the cell spheres could change their size or shape, producing tissue with different properties than desired.

"We have now succeeded in combining the advantages of both approaches – using an extremely high-resolution 3D printing method that we have been researching here at TU Wien for years," says Ovsianikov.

This printing technique is called two-photon polymerization and uses a light-sensitive polymer material that is cured with a laser beam at the desired positions. This allows structures to be produced with an accuracy in the range of less than 1µm.

Ovsianikov and his team used this laser method to create filigree, highly porous scaffolds with a diameter of just under a third of a millimetre. The design of these micro-scaffolds allows the rapid generation of cell agglomerates inside. At the same time, the cells are protected from external mechanical damage, similar to the way a rally driver is protected by a roll-cage.

"These cell-filled scaffolds are relatively easy to handle and can coalesce," explains Ovsianikov. "When many of them are brought into direct contact, it is possible to create large tissue constructs with a high initial cell density in a short time. Still, we can control the mechanical properties of the structure well."

The underlying concept of this novel tissue engineering strategy was originally presented by the research group in 2018. Now, for the first time, they have shown that the method actually works.

"We were able to show that the method actually delivers the benefits we were hoping for," says Ovsianikov. "We used stem cells for our experiments, which can be induced to produce either cartilage or bone tissue. We were able to show that the cells from neighbouring scaffold units do indeed merge and actually form a single tissue. In doing so, the structure retains its shape. In the future, these scaffold units could even be made injectable for use in minimally invasive surgery."

This story is adapted from material from TU Wien, with editorial changes made by Materials Today. The views expressed in this article do not necessarily represent those of Elsevier. Link to original source.