Is it possible to grow tissue within the laboratory, for instance to switch injured cartilage? At TU Wien (Vienna), a crucial step has now been taken towards creating substitute tissue within the lab — using a method that differs significantly from other methods used around the globe.
A special high-resolution 3D printing process is used to create tiny, porous spheres fabricated from biocompatible and degradable plastic, that are then colonized with cells. These spheroids can then be arranged in any geometry, and the cells of the several units mix seamlessly to form a uniform, living tissue. Cartilage tissue, with which the concept has now been demonstrated at TU Wien, was previously considered particularly difficult on this respect.
Tiny spherical cages as a scaffold for the cells
“Cultivating cartilage cells from stem cells just isn’t the largest challenge. The major problem is that you simply often have little control over the form of the resulting tissue,” says Oliver Kopinski-Grünwald from the Institute of Materials Science and Technology at TU Wien, one in every of the authors of the present study. “This can be resulting from the proven fact that such stem cell clumps change their shape over time and sometimes shrink.”
To forestall this, the research team at TU Wien is working with a brand new approach: specially developed laser-based high-resolution 3D printing systems are used to create tiny cage-like structures that appear to be mini footballs and have a diameter of only a third of a millimeter. They function a support structure and form compact constructing blocks that may 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 manner, we will reliably produce tissue elements wherein the cells are evenly distributed and the cell density could be very high. This might not have been possible with previous approaches,” explains Prof. Aleksandr Ovsianikov, head of the 3D Printing and Biofabrication research group at TU Wien.
Growing together perfectly
The team used differentiated stem cells — i.e. stem cells that may now not become any variety of tissue, but are already predetermined to form a selected variety of tissue, on this case cartilage tissue. Such cells are particularly interesting for medical applications, but the development of larger tissue is difficult in relation to cartilage cells. In cartilage tissue, the cells form a really pronounced extracellular matrix, a mesh-like structure between the cells that always prevents different cell spheroids from growing together in the specified way.
If the 3D-printed porous spheres are colonized with cells in the specified way, the spheres may be arranged in any desired shape. The crucial query is now: do the cells of various spheroids also mix to form a uniform, homogeneous tissue?
“This is precisely what now we have now been in a position to show for the primary time,” says Kopinski-Grünwald. “Under the microscope, you may see very clearly: neighboring spheroids grow together, the cells migrate from one spheroid to the opposite and vice versa, they connect seamlessly and end in a closed structure with none cavities — in contrast to other methods which have been used up to now, wherein visible interfaces remain between neighboring cell clumps.”
The tiny 3D-printed scaffolds give the general structure mechanical stability while the tissue continues to mature. Over a period of a couple of months, the plastic structures degrade, they simply disappear, forsaking the finished tissue in the specified shape.
First step towards medical application
In principle, the brand new approach just isn’t limited to cartilage tissue, it may be used to tailor different sorts of larger tissues resembling bone tissue. Nevertheless, there are still a couple of tasks to be solved along the way in which — in spite of everything, unlike in cartilage tissue, blood vessels would also must be incorporated for these tissues above a certain size.
“An initial goal could be to supply small, tailor-made pieces of cartilage tissue that may be inserted into existing cartilage material after an injury,” says Oliver Kopinski-Grünwald. “In any case, now we have now been in a position to show that our method for producing cartilage tissue using spherical micro-scaffolds works in principle and has decisive benefits over other technologies.”
