Scaffold-free non-toxic biofabrication in a high magnetic field

There is a high demand for artificial tissue, for instance for scientific (cancer) research and as donor organs. Bioassembly on a surface ('scaffold') has several disadvantages. An alternative is magnetic levitational bioassembly. Levitation using permanent magnets is possible, but only in a toxic concentration of a paramagnetic salt solution. Researchers from Russia and HFML-FELIX now report that magnetic levitational bioassembly with a non-toxic, low concentration of a paramagnetic medium in high magnetic field is technologically feasible. Moreover, the experimental results confirm that it can be used  as a cost-effective alternative to microgravity research at the ISS.

In the early 1990s, the potential of levitation in air of water and other diamagnetic substances was demonstrated.  Since then, the principles of magnetic levitation have been used successfully and broadly in different areas of technology and industry. In 1997, Andre Geim performed diamagnetic levitation of a living organism (the famous flying frog) in air at the HFML, which was a breakthrough in the area of magnetic levitation.

In cell biology, as cells or tissue spheroids (cell aggregates) are diamagnetic, it has been proposed to achieve their levitation by using a paramagnetic medium. This approach avoids the use of “labels” of any type, such as magnetic nanoparticles, which are cytotoxic and proved to accumulate in human organisms after implantation of tissue-engineered constructs containing nanoparticles.

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Construct assembly under high magnetic field levitation. a) polystyrene beads assembling at 0.5 mM gadobutrol and magnetic field intensity of 22 Т; b) tissue spheroids assembling until a stable construct was obtained at 0.8 mM gadobutrol and magnetic field intensity of 19 Т; c) construct assembled after 3 hours at 19 Т (insert circle shows a histological section of the construct); d) the curves of levitation conditions depending on the gadobutrol concentration and magnetic field intensity applied for tissue spheroids (red curve) and polystyrene beads (blue curve)

For the described experiments, a Gadolinium(III)-chelate contrast agent was selected, which is known to have the lowest possible toxicity. However, at high concentrations, it is still potentially toxic for cells and tissue spheroids, because of the osmotic pressure imbalance due to excessive use of ions in the paramagnetic medium. An obvious dilemma - high concentration of gadolinium enables magnetic levitation but is relatively toxic, whereas a low, non-toxic concentration of gadolinium does not allow magnetic levitation with permanent magnets. The solution is to perform the levitation at a low concentration of gadolinium but using a very high magnetic field.

Using a magnetic field of up to 31 Tesla at the HFML, researchers performed magnetic levitational assembly of tissue constructs from living spheroids. The construct from tissue spheroids partially fused after 3 hours of levitation. The analysis of viability after prolonged exposure to the magnetic field showed the absence of significant cytotoxicity or morphology changes in the tissue spheroids. This means that the high magnetic field acts as a non-toxic, temporal and removable support. The researchers demonstrate that formative biofabrication of tissue-engineered constructs from tissue spheroids in the high magnetic field is a promising research direction.


Scaffold‐free and label‐free biofabrication technology using levitational assembly in a high magnetic field, V.A. Parfenov, V.A. Mironov, K.A. van Kampen, P.A. Karalkin, E.V. Koudan, F.DAS Pereira, S.V. Petrov, E.K. Nezhurina, O.F. Petrov, M.I. Myasnikov, F.X. Walboomers, H.Engelkamp, P.C.M Christianen, Y.D. Khesuani, L.Moroni, C. Mota, Biofabrication 12,4 (2020).

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Hans Engelkamp