Development of a new tissue engineering strategy

It’s an old dream of medicine: if arbitrary types of tissue could be produced artificially from stem cells, then wounds could be healed with the body’s own cells, and one day it might even be possible to produce artificial organs. However, it is difficult to obtain cells in the desired shape. The methods that have existed so far can be divided into two fundamentally different categories: either one first creates small tissue building blocks, such as round cell agglomerates or flat cell sheets, and then assembles them, or one initially creates a thin and porous scaffold which is then cultured with cells. Both approaches have advantages and disadvantages.

At TU Wien (Vienna), a third approach has now been developed: Using a special laser-based 3D printing technique, micro-scaffolds with a diameter of less than a third of a millimeter can be produced, which can accommodate thousands of cells. In this way, a high cell density is present from the start, but one still has the flexibility to adapt the shape and the mechanical properties of the structure.

With scaffolding or without?

“The scaffold-based approaches that have been developed so far have great advantages: if you create a porous scaffold first, you can precisely define its mechanical properties,” says Dr. Olivier Guillaume, lead author of the current study, which is researching at TU. Wien in the team of Professor Aleksandr Ovsianikov at the Institute of Materials Science and Technology. “The scaffold can be soft or hard as needed, it is made of biocompatible materials that break down in the body. They can even be equipped with special biomolecules that promote tissue formation.”

The disadvantage, however, is that it is difficult to quickly and completely fill such a scaffold with cells. A lot of manual work is still required here today, although research is already being done on automated processes. Especially with large scaffolds, it takes a long time for cells to migrate inside the structure; often the cell density remains very low and inhomogeneous.

The situation is completely different if no such scaffolding is used. It is also possible to simply grow clusters of small cells, which are then assembled into the desired shape and finally fuse together. With this technique, the number of cells is important from the start, but there is practically no possibility of intervening in the process. For example, it may happen that the cellular spheres change in size or shape and that the tissue ends up with properties different from those desired.

Living cells meet high resolution 3D printing process

“We have now succeeded in combining the advantages of both approaches – using a very high resolution 3D printing method that we have been studying here at TU Wien for years,” says Professor Aleksandr Ovsianikov.

This technique, two-photon curing, uses a light-sensitive material that is cured with a laser beam at exactly the desired positions. In this way, structures can be produced with an accuracy on the order of less than a micrometer.

This laser method is now used to create filigree and highly porous scaffolds with a diameter of just under a third of a millimeter. The design of these micro-scaffolds allows the rapid generation of cell clusters inside. At the same time, the cells are protected from external mechanical damage, in the same way that a rally driver is protected by a racing car roll cage.

“These cell-filled scaffolds are relatively easy to manipulate and can fuse together,” says Aleksandr Ovsianikov. “When many of them are brought into direct contact, it is possible to create large tissue constructs with high initial cell density in a short time. Yet, we can control the mechanical properties of the structure well.”

Cartilage and bone as primary target tissues

The underlying concept of this new tissue engineering strategy was already presented in detail by the research group in 2018. Today, for the first time, it was possible to show that this method actually works: “We were able to show that the method provides the benefits we hoped for,” says Aleksandr Ovsianikov. “We used stem cells for our experiments, which can be induced to produce cartilage or bone tissue. We were able to show that cells from neighboring scaffold units do indeed fuse together and actually form a single tissue. In doing so, the structure retains its shape. In the future, these scaffold units may even be made injectable for use in minimally invasive surgery.

Reference: Guillaume O, Kopinski-Grünwald O, Weisgrab G, et al. Hybrid spheroid microscaffolds as modular tissue units to construct macro-tissue assemblies for tissue engineering. Acta Biomater., 2022. doi: 10.1016/j.actbio.2022.03.010

This article was republished from the following documents. Note: Material may have been edited for length and content. For more information, please contact the quoted source.

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