Researchers engineer human muscle tissue through 3D printing

Health and Wellness 12. mar 2023 3 min Group Leader and Associate Professor Johan Ulrik Lind Written by Kristian Sjøgren

To realise the dream of 3D-printing human muscles, researchers developed a special type of nanofibres that can be mixed with muscle cells to give them the right structure and guiding capabilities to form muscle fibres. A researcher says that the goal is to eventually be able to 3D-print living models of the human body.

Being able to 3D-print muscles sounds like something Mary Shelley could have concocted, but researchers from the Technical University of Denmark are working on this.

The researchers aim to develop the technology to enable both healthy and diseased muscles to be printed to study metabolic diseases, how muscle tissues act under exercise and how insulin resistance is induced.

The researchers are now one step closer to realising this vision. They showed that mixing living cells with cellulose nanofibres can create the structure needed to make real muscle fibres.

“The ambition is to develop a platform to enable the 3D-printing and culturing of muscle cells for use in laboratory experiments that require muscles with very specific properties. Now we can show that we can make the cells grow directionally in the same way as natural muscle fibres, and a future aim is to be able to integrate other types of cells into our 3D-printing ink so that we can eventually create a more complicated tissue that is more like natural muscle tissue,” explains a researcher involved in the study, Johan Ulrik Lind, Group Leader and Associate Professor, Department of Health Technology, Technical University of Denmark, Kongens Lyngby.

The research has been published in ACS Applied Materials & Interfaces.

Cells must act naturally

3D-printing living tissue requires a bioprinter that uses a mixture of living cells and structural biomaterials, which are mixed together and sprayed out into the desired structure using a syringe resembling a small cake-decorating nozzle.

For example, to make a muscle, they tell the 3D printer what the muscle should look like, and then the printer creates exactly that structure.

That sounds a little too simple. The cells must be able to grow on the structural biomaterial comparable to what happens in the body.

Researchers have long struggled to develop a biomaterial that makes the attached cells act as the cells ideally do to form something that acts naturally.

“Muscle tissue tends to grow along fibres so that these end up forming muscle fibres similar to muscles in humans. But if the muscle cells grow on fibres that are too large or too small, they do not form relevant muscle fibres, which affects the function and relevance of the tissue,” says Johan Ulrik Lind.

Making structure fibres from cellulose

The researchers developed a new type of partly negatively charged cellulose nanofibres and used them in combination with muscle cells to 3D-print muscle tissue.

Cellulose is the most common biopolymer on the planet and comprises most of all plant material, from stems and trunks to branches and leaves.

The researchers produced the cellulose nanofibres by selectively breaking down the micro- and macrofibres in plant material.

The macrofibres are the large threads that are visible in splitting a piece of firewood, and they comprise smaller fibres, which in turn comprise even smaller fibres. Muscle cells are built similarly.

“We break down cellulose to a size at which it resembles collagen, the structural molecule of muscles. We can do this very cheaply, which makes cellulose attractive compared with bioprinting,” says Johan Ulrik Lind.

Cellulose nanofibres have exactly the right properties

The properties of the cellulose nanofibres make them a promising candidate for bioprinting muscles.

The nanofibres and microfibres orient themselves towards the direction in which the mixture of cellulose and muscle cells is injected. This means that, as the muscle cells grow, they elongate lengthwise by a flow line.

This also means that the cells can fuse and form long muscle fibres, which is exactly what the researchers want from 3D printing, since this mimics real muscles.

Johan Ulrik Lind says that nanofibres are promising for bioprinting for two reasons.

  • The nanofibres provide structural strength to the cells. The nanofibres are thus neither too large nor too small in relation to guiding the growth direction of the muscle cells into muscle fibres. Cellulose also has a soft structure like gelatine, which is good to shape in 3D, without the material being too solid, and muscle cells stick well to cellulose.
  • Cellulose is liquid enough that the researchers can put it in the 3D printer cartridge. Imagine being able to spray cake cream or whipped cream in a predetermined shape with a cake nozzle, but this would probably be quite difficult with cold butter or even milk. Cellulose has just the right viscosity.

“We can thus control the process and the direction of the muscle fibres, which is important to make large muscle fibres to study in the laboratory. In our experiments, we have given the muscles reasonable characteristics that we have decided to continue using in our future research,” explains Johan Ulrik Lind.

The development of the cellulose nanofibres is only a small step towards the ambition of mimicking actual muscles.

In the future, the researchers will continue to develop their platform so that they can eventually create life-like muscles with all the other associated types of cells, including blood vessels and motor neurons.

“We must also determine how we can influence their function, such as changing their metabolism, so that they can become relevant models for studying fat metabolism, insulin resistance or obesity,” concludes Johan Ulrik Lind.

Transparent and cell-guiding cellulose nanofiber 3D printing bioinks” has been published in ACS Applied Materials & Interfaces. The Danish Diabetes and Endocrine Academy and the Novo Nordisk Foundation have awarded grants for research by co-author Jonas R. Knudsen.

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