Scientists from the Institute of Materials Science and Technology at TU Wien in Vienna have created a unique method for 3D printing synthetic biological tissue.
Using high-resolution SLA 3D printing, they are able to fabricate minuscule, porous spheres from plastic that is both biocompatible and able to disintegrate. They then colonize these tiny, football-shaped scaffolds, known as spheroids, with stem cells and arrange them into specific configurations.
In their research which was published in Acta Biomaterialia, the scientists from TU Wien demonstrated that these cells could then be merged to produce live cartilage tissue. As a sturdy connective tissue that dwells in numerous areas of the body to safeguard joints and bones, cartilage is traditionally very challenging to manufacture using standard methods.
The researchers see their findings as potential game-changers in developing artificial tissue for medical procedures to replace damaged cartilage.
The new approach is not limited to cartilage tissue, and could be used to tailor different kinds of larger tissues such as bone tissue. Key challenges, such as the incorporation of blood vessels into larger 3D printed tissue, would need to be overcome before the researcher’s 3D printing methodology can be expanded into more complex medical applications.
“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,” stated study author 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.”
3D printed spheroid, filled with living cells. Image via TU Wien.
Fabricating cartilage tissue with 3D printed cell scaffolds
As highlighted by Kopinski-Grünwald, crafting cartilage tissue from stem cells regularly presents a predicament, chiefly due to the insufficient control over the eventual shape. This complexity is also a byproduct of changes in the shape of stem cell clusters over time, often leading to shrinkage, he clarified.
However, the innovative method introduced by the team at TU Wien manages to bypass this complication. The approach involves the utilization of specially-designed, laser-aided high-resolution resin 3D printers. The team employed two-photon polymerization to construct microscopic spherical scaffold structures with a minimal diameter of just a third of a millimeter, or 333 µm.
Following this, the researchers integrated differentiated stem cells into the tiny spheroidal structures. The unique property of these cells is such that they are inhibited from developing into any tissue type. Instead, they are directed to form a designated tissue type, cartilage in this scenario.
Once added to the 3D printed scaffolds, the cells quickly fill the small volume. According to Professor Aleksandr Ovsianikov, head of the 3D Printing and Biofabrication research group at TU Wien, this allowed the team to reliably produce tissue elements with evenly distributed and high-density cell formations.
The 3D printed cell support structures ultimately form compact building blocks that can then be assembled into any required shape or geometry.
The spherical scaffolds provide stability to the overall structure as the tissue matures. 3D printed in biodegradable plastic, the support structure then dissolves over the space of a few months, leaving behind the complete tissue in its final form.
Please note that there was an image originally placed here showing a close-up of a 3D printed spheroid via the TU Wien, but it has been removed as per instructions.
While differentiated stem cells are already utilized in various medical applications, the use of cartilage cells in the construction of larger tissue poses challenges. For instance, cartilage tissue cells form a pronounced extracellular matrix. This mesh-like structure is located between the cells, and often prevents different cell spheroids from growing together in the desired way.
The TU Wien researchers’ process successfully overcomes this obstacle. The team is reportedly the first to combine cells from different spheroids into uniform, homogenous, and completely closed cartilage tissue.
“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,” noted Kopinski-Grünwald.
The spheroids in which living cells are grown can be assembled into almost any shape.
3D printing artificial human tissue
3D printing human tissue for medical applications is certainly a growing field. 3D expert surveys on 3D printing trends and the future of 3D printing highlighted the medical industry as being a sector which will continue to experience significant 3D printing innovation.
A team of scientists from University of Sydney and the Children’s Medical Research Institute (CMRI) at Westmead leveraged 3D photolithographic printing to create functional human tissue capable of accurately mimicking human organs.
“Why did the 3D printer go to therapy? Because it had too many layers of unresolved issues!”
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