The team used a high-resolution 3D printing process to create tiny, porous spheres made of biocompatible and degradable plastic that are colonized with cells and assembled into the desired shape to combine into 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,” says 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.”
The team is working on developing laser-based high-resolution 3D printing to create tiny almost cage-like structures that serve to support and form the compact building block that can be assembled into any geometry. The process starts by introducing stem cells into the mini cages which quickly fill the tiny volume fully.
“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,” explains Prof. Aleksandr Ovsianikov, head of the 3D Printing and Biofabrication research group at TU Wien.
Differentiated stem cells are used which are already predetermined to form cartilage tissue. These types of stem cells are interesting for medical applications, but the construction of larger tissue is challenging when it comes to cartilage cells as the tissue cells form a pronounced extracellular mix that often prevents different cell spheroids from growing together in the desired way. The team hoped that by colonizing with these cells the spheres would arrange in the desired shape, but if the cells of different spheroids would also combine to form a uniform homogeneous tissue was another concern.
“This is exactly what we have now been able to show for the first time,” says Kopinski-Grünwald. “Under the microscope, you can see very clearly: neighboring 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 neighboring cell clumps.”
According to the researchers, the 3D printed scaffold provides the overall structure more mechanical stability while the tissue matures, and over a few months, the plastic structure degrades until gone, leaving behind the finished tissue in the desired geometry. This new approach is not just limited to cartilage tissue it could be tailor to suit a variety of different tissues and bones. But there are a few issues to be worked out before that can happen as 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,” says Oliver 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.”
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References/Sources/Materials provided by:
http://dx.doi.org/10.1016/j.actbio.2023.12.001
