3D Printed Artificial Cartilage: A Breakthrough in Biomedical Engineering

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Can tissue be grown in a lab to replace damaged cartilage, for example? At TU Wien (Vienna), a crucial step has been taken towards creating replacement tissue in a lab, using a technique that differs significantly from other methods used around the world.

A unique high-resolution 3D printing process is used to fabricate small, porous spheres made of biocompatible and degradable plastic, which are then populated with cells. These spheroids can be arranged in any shape, and the cells of the different units seamlessly combine to form a uniform, living tissue. Cartilage tissue, which was previously considered particularly challenging, has now been demonstrated at TU Wien.

Small spherical cages as a scaffold for the cells

“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,” explains 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 this, the research team at TU Wien is working with a new approach: specially developed laser-based high-resolution 3D printing systems are used to create tiny cage-like structures that resemble mini footballs and have a diameter of just a third of a millimeter. They function as a support structure and form compact building blocks that can then be assembled into any shape.

Stem cells are first introduced into 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,” explains Prof. Aleksandr Ovsianikov, head of the 3D Printing and Biofabrication research group at TU Wien.

Perfectly growing together

The team used differentiated stem cells, stem cells that are already predetermined to form a specific type of tissue, in this case cartilage tissue. Such cells are particularly interesting for medical applications, but constructing larger tissue is challenging with cartilage cells. In cartilage tissue, the cells form a very pronounced extracellular matrix, a mesh-like structure between the cells that often prevents different cell spheroids from growing together as desired.

If the 3D-printed porous spheres are colonized with cells in the desired way, the spheres can be arranged in any desired shape. The crucial question is now: do the cells of different spheroids also combine to form a uniform, homogeneous tissue?

“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.”

The tiny 3D-printed scaffolds provide the overall structure with mechanical stability while the tissue continues to mature. Over a period of a few months, the plastic structures degrade, they simply disappear, leaving behind the finished tissue in the desired shape.

First step towards medical application

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. However, there are still a few tasks to be solved along the way after all, unlike in cartilage tissue, blood vessels would also have to be incorporated for these 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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