TU Wien
At the Vienna University of Technology, also known as TU Wien, researchers have taken a step towards creating replacement tissue, which could possibly used to replace injured cartilage, in the lab using 3D printing.
A special, high resolution 3D printing process is used to create tiny, porous spheres made of biocompatible and degradable plastic, which are then colonised with cells. These spheroids can then be arranged in any geometry, and the cells of the different units combine to form a uniform, living tissue.
“Cultivating cartilage cells from stem cells is not the biggest challenge. The main problem is that you usually have little control over the shape of the resulting tissue,” said Oliver Kopinski-Grünwald from the Institute of Materials Science and Technology at TU Wien, one of the authors of the current study. “This is also due to the fact that such stem cell clumps change their shape over time and often shrink.”
To prevent these issues, the research team at TU Wien is working with a new approach. They are using specially developed laser-based high resolution 3D printing systems to create tiny cage-like structures that look like mini footballs and have a diameter of a third of a millimetre. They serve as a support and form compact building blocks that can be assembled into any shape.
Stem cells are first introduced in these football-shaped mini cages, which quickly fill the tiny volume completely.
“In this way, we can reliably produce tissue elements in which the cells are evenly distributed and the cell density is very high. This would not have been possible with previous approaches,” said Professor Aleksandr Ovsianikov, Head of the 3D Printing and Biofabrication research group at TU Wien.
The team used differentiated stem cells, which are stem cells that can no longer develop into any type of tissue, but are already predetermined to form a specific type of tissue, in this case cartilage tissue. Such cells are particularly interesting for medical applications, but the construction of larger tissue is challenging when it comes to cartilage cells.
TU Wien
In cartilage tissue, the cells form a very pronounced extracellular matrix according to the team, a mesh-like structure between the cells that often prevents different cell spheroids from growing together in the desired way.
If the 3D printed porous spheroids are colonised with cells in the desired way, the spheroids can be arranged in any desired shape. The team says the crucial question is now: ‘do the cells of different spheroids also combine to form a uniform, homogenous tissue?’
“This is exactly what we’ve been able to show for the first time,” says Kopinski-Grünwald. “Under the microscope, you can see very clearly: neighbouring spheroids grow together, the cells migrate from one spheroid to the other and vice versa, they connect seamlessly and result in a closed structure without any cavities – in contrast to other methods that have been used so far, in which visible interfaces remain between neighbouring cell clumps.”
The tiny 3D printed scaffolds give the overall mechanical stability while the tissue continues to mature according to the team. Over a period of a few months, the plastic structures degrade, they disappear, and leave behind the finished tissue in the desired shape.
In principle, the new approach is not limited to cartilage tissue, it could also be used to tailor different kinds of larger tissues such as bone tissue. The team says to achieve this there are still a few tasks to be solved along the way, as unlike in cartilage tissue, blood vessels would also have to be incorporated for tissues above a certain size.
“An initial goal would be to produce small, tailor-made pieces of cartilage tissue that can be inserted into existing cartilage material after an injury,” said Kopinski-Grünwald. “In any case, we have now been able to show that our method for producing cartilage tissue using spherical micro-scaffolds works in principle and has decisive advantages over other technologies.”
Read more 3D bioprinting news.
