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International Journal of Bioprinting Magnetic (Bio)inks for tissue engineering

Magnetic hydrogels may be employed in soft robotics after having been exposed to external forces through
due to their remote controllability. These actuators mainly dynamic covalent crosslinking or covalent and non-
function through the shape change that is induced by an covalent interactions. These features make them very
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external magnetic field, which exerts a force in the MNPs interesting materials for tissue engineering applications
which, in turn, is transmitted to the polymeric matrix. since they can extend the materials’ longevity while
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Moreover, the 3D printing process allows the fabrication maintaining their original characteristics. 80
of magnetic hydrogels of various shapes; therefore, this
method can be applied to produce soft robots for different Using a mixture of N-carboxyethyl chitosan (CEC)
purposes. and aldehyde hyaluronic acid (AHA), Nardecchia et al.
formulated an injectable bioink loaded with magnetic
In order to test the ability of a 3D printing strategy to particles to introduce anisotropy in a construct through
build complex and magnetically-responsive structures, the application of external magnetic fields. The mixture
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Simińska-Stanny et al. printed alginate and methylcellulose of these compounds led to the formation of Schiff base—
hydrogels containing a gradient of PAA-stabilized MNPs, compounds possessing a double bond connecting a carbon
into various shapes such as wheels, cantilevers, or cubes. and a nitrogen atom —bonds between amino groups of
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The ink possessed a shear-thinning behavior due to CEC and aldehyde groups of AHA. The results of this study
the presence of methylcellulose, and this behavior was showed that the magnetic particles aligned themselves in
enhanced by the introduction of MNPs in the system, even the direction of the magnetic field, and that they improved
though it caused a decrease in the viscoelastic modulus the strength of the overall matrix. Additionally, there was
of the ink. The printed structures could be remotely also evidence that hysteresis could be controlled via an
controlled through the application of an external magnetic external magnetic field, which enables the tuning of the
field, and this control depended on the organization of the mechanical properties of the hydrogel once it has been
layers within the hydrogel. Regarding cell viability, L929 injected. The same type of chemical bond was used by Chen
fibroblasts were able to maintain an adequate viability et al., who fabricated a hydrogel made of carboxymethyl
in the magnetic hydrogels (>85%), demonstrating the chitosan and calcium pre-crosslinked oxidized gellan
biocompatibility of this material. Besides their efforts gum, complemented by magnetic hydroxyapatite/gelatin
in fabricating hydrogels for muscle tissue engineering microspheres loaded with antibacterial drugs to be applied
applications, Tognato et al. also reported the use of a in bone tissue engineering. The incorporation of this type
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GelMA ink to 3D-print a soft robot in the shape of a of particles within the scaffold increased its mechanical
starfish whose flapping motion could be guided by external stability and promoted a more sustained drug release
alternating magnetic fields. These experiments prove that without affecting cell viability. Nonetheless, the magnetic
using magnetic hydrogels for the control of constructs susceptibility of the obtained structures was not tested.
can elicit an effect in the body when exposed to external This type of crosslinking bonds has the advantage of not
magnetic fields. 6
requiring any toxic initiators nor UV light for crosslinking
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5. Injectable magnetic hydrogels and their to occur, which renders them biocompatible and eligible
to be used in combination with cells. Furthermore, it has
potential use in 3D (bio)printing been shown to be usable in 3D (bio)printing applications
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One of the main characteristics for an hydrogel to be with no effects on the long-term cell viability, thus proving
eligible for 3D (bio)printing purposes is its ability to be this type of reaction is compatible with the desired purpose.
injected through a nozzle: not only must the hydrogel 5
possess rheological properties that allow it to hold its To target volumetric muscle loss, Wang et al. developed
shape after printing, but it also must possess an adequate an injectable GelMA hydrogel with magnetic nanofibers
interface compatibility with the nozzle’s material, so as not obtained by electrospinning. The hydrogel precursor
to increase the pressure needed to extrude it nor to cause an solution was mixed with the fibers and C2C12 cells, and
augmented shear stress that can, subsequently, reduce cell the hydrogel was curated using UV light. Afterward, the
viability within the printed scaffold. Thus, research in the fibers were aligned using an external magnetic field, with
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injectability of hydrogels has direct impact in their potential this alignment leading to increased cell adhesion and
to be used in 3D (bio)printing strategies. With this in mind, increased myotube length and number. Furthermore,
this section summarizes some of the recent advances made when implanted into a mouse model, the magnetic
in the fabrication of injectable magnetic hydrogels. construct enhanced angiogenesis in comparison with
the control (mice implanted with the hydrogel without
Self-healing hydrogels are quite appealing for 3D (bio) magnetic fibers) and sham (surgery was performed, but
printing. This type of hydrogels can recover their structure the mice were not implanted with any hydrogel) groups.

Volume 10 Issue 1 (2024) 13 https://doi.org/10.36922/ijb.0965