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

higher than the ones cultured on scaffolds consisting of to increased viscosity and enhanced shear-thinning effects
only one of the two layers. The obtained results highlight on the precursor ink. This study demonstrated that a higher
the importance of the microarchitecture of the scaffold, PAA:MNP ratio led to a better quality of the 3D-printed
and the strategy followed in this work shows how structures. The application of a magnetic field decreased the
magnetic stimulation and 3D (bio)printing can both be equilibrium swelling degree of the scaffolds and caused a
synergistically combined to recreate more native-like deformation of the microstructure in its direction. Therefore,
structures. Nonetheless, the inkjet printing approach used these works show the need to optimize ink formulations in
in such work is most suitable for printing low-viscosity order to achieve the desired outcomes concerning printability,
solutions, which narrows the list of biomaterials to be biocompatibility, and magnetic response, paving the way
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used, limits the cell concentration that can be deposited, for the application of magnetically-responsive hydrogels
and when applied to thicker and complex 3D geometries, in cartilage tissue engineering strategies. Importantly, the
may result in structures that are not able to sustain their hydrogel formulation should be tested in terms of its ability
physical integrity. Such limitation can be overcome by to promote cell viability, proliferation, and chondrogenic
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resorting to extrusion bioprinting approaches. differentiation.
Another strategy to manipulate chondrocyte phenotype 4.2.2. Bone tissue engineering
using magnetic stimulation has been explored by Choi Hydrogels are usually not used as materials to substitute
et al., who developed a hydrogel made from oxidized bone due to their lower mechanical stiffness in comparison
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hyaluronate, glycol chitosan, adipic acid dihydrazide, and with this type of hard tissue. Still, magnetic hydrogels
superparamagnetic iron oxide nanoparticles (SPIONs), can be used in bone tissue engineering as vehicles to
and tested the printability of the bioink using an extrusion induce regeneration of bone defects. The introduction
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3D bioprinter. The cell viability and the chondrogenic of magnetic components within scaffolds for bone tissue
differentiation of ATDC5 cells in vitro were also assessed. engineering can allow the creation of an anisotropic
The results obtained showed that the introduction of identity characteristic of this type of tissue, as well as
SPIONs in the matrix led to a decrease in the mechanical increase the mechanical stiffness of hydrogels that would
properties of the hydrogel, corresponding to a decrease in otherwise be too soft for this application. Furthermore,
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its storage modulus, while cell viability was not affected by a 3D (bio)printing approach can allow for a more precise
the magnetic stimulation, SPIONs, or the 3D bioprinting replication of bone’s native porous microarchitecture. 68
process itself. The application of magnetic fields to the Targeting potential bone tissue engineering
tissue constructs obtained also resulted in an increase applications, Li et al.’s work focused on the 3D extrusion
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in the expression of SOX9 and COL2 genes, suggesting a printing of a hydrogel consisting of a mixture of polyvinyl
positive effect on chondrogenic differentiation. alcohol, sodium alginate, and hydroxyapatite (PVA/
In a different study, Spangenberg et al. formulated SA/HA) with graphene oxide functionalized with iron
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a hydrogel composed of alginate and methylcellulose nanoparticles (magnetic graphene oxide, MGO). Similar
(algMC) with embedded magnetite microparticles. to previous studies, the authors concluded that the
The authors observed that a condition with 25% w/w of incorporation of hydroxyapatite in the structure improved
embedded particles in the hydrogel showed appropriate the mechanical properties of the scaffold, and that the
rheological properties, allowing for a smooth ink addition of MGO had beneficial effects in cell adhesion
extrusion, magnetization, and printability. An increase in without any cytotoxicity effects. The ability of the scaffolds
the scaffolds’ Young’s modulus was also observed following to promote the osteogenic differentiation of rat bone
the addition of particles, with the 25% w/w of particles marrow-derived MSCs (BMSCs) or to inhibit tumor
hydrogel formulation presenting values similar to the ones growth through hyperthermia in vivo was also analyzed.
described for the native cartilage tissue, at values of 627 ± 53 These results highlight the potential application of these
kPa and 1.03 ± 0.48 MPa, respectively. Cytocompatibility scaffolds both in bone regeneration and tumor targeting
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assays performed using an immortalized MSC cell line strategies. Nevertheless, it is worth noting that in this study
showed that cells cultured in a plain algMC scaffold the printing process did not contain cells embedded in the
presented a slightly decreased initial cell viability, which ink, which could be a valuable addition to the performance
however increased over the 21 days in culture. of the hydrogel in vivo via, for example, secretion of growth
factors that would further enhance bone regeneration.
An alginate and methylcellulose (MC) hydrogel
containing embedded poly(acrylic acid) (PAA) stabilized- 4.2.3. Muscle tissue engineering
MNPs (PAA-MNPs), mixed at different ratios, was developed Muscle tissue engineering has also been explored as an
by Podstawczyk et al. The addition of the PAA-MNPs led application in which magnetic hydrogels can play a role.
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Volume 10 Issue 1 (2024) 11 https://doi.org/10.36922/ijb.0965