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

When combined with hydrogels, MNPs can promote use of this bioreactor system allowed the stimulation of the
cell alignment upon magnetic stimulation, which is hydrogel while it was being fabricated, thus permitting a
advantageous to mimicking the native muscle tissue closer control of the structure’s manufacture.
anisotropy. Moreover, the ability to respond to an external Adding MNPs to hydrogels has great implications in
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magnetic field allows the simulation of muscle contraction, muscle tissue engineering, since it allows for a close control
meaning that these materials can potentially be used as over their motion within the scaffold, as well as provides the
artificial muscles. 67
hydrogel structure with shape memory capabilities. 3D
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To address the ability of magnetically-responsive (bio)printing is also a valuable approach to this field, since
hydrogels to respond to external stimuli, Tognato et al. it allows to precisely deposit material that can, for example,
fabricated a cell-laden anisotropic gelatin methacryloyl mimic the fascicular structure of skeletal muscle tissue or
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(GelMA) hydrogel that could change its conformation to fabricate heart patches for cardiac regeneration. Thus,
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when stimulated. The hydrogel was formed through the combination of these two strategies is a path that can
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the application of an external magnetic field of very low bring significant advances to the area.
intensity (0.02 T), which induces orientation of the iron
oxide nanoparticles (IOPs), followed by exposure to 4.2.4. Other applications
ultraviolet (UV) light for further crosslinking. The authors Magnetic hydrogels can also have antibacterial activity.
claimed that it is possible to tune the size and length of The MNPs embedded within the polymeric matrix
IOP filaments, as well as the distance between filaments. can potentially induce bacterial death through various
Cell seeding and encapsulation assays were performed mechanisms, namely electrostatic interactions with the
using human BMSCs and C2C12 mouse myoblast cells, cell membrane, potentially disrupting it and causing
respectively. The authors observed that using aligned IOP the leakage of cytoplasmic components. Furthermore, it
filaments promoted the orientation of both types of cells in has been suggested that there is a higher level of reactive
the IOP filaments direction, and C2C12 cells encapsulation oxygen species (ROS) formed on the surface of the MNPs,
on these hydrogels resulted in an increased number of with these ROS playing a major role in the destruction of
mature multinucleated myotubes. These results show that cellular components such as proteins and DNA. Another
the recapitulation of the fiber alignment of native muscle path that can cause bacterial death involves a photocatalytic
tissue is possible in an in vitro setting. Furthermore, effect that occurs when MNPs are stimulated with visible
there are already existing reports on the bioprinting of a light, inducing changes in their electronic structure and
GelMA bioink containing C2C12 cells which achieved originating free electrons, that can induce formation of
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good cell viability (> 90%) even after UV exposure. These ROS and cause cell death. Despite all these potential
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results mean that these cells can withstand the stress of paths to cell death, bactericidal effect of MNPs is executed
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the extrusion procedure and the posterior crosslinking mainly through ROS production, chlorosis, and hypoxia.
reaction, showing the potential of the 3D (bio)printing of a This type of approach is especially relevant in countering
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magnetic bioink for this application. antibiotic-resistant microorganisms or preventing
infections post-implantation by providing a non-invasive
In order to stimulate a cell-laden hydrogel to modulate and non-harmful solution.
their morphology and differentiation, Ajiteru et al.
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used an interesting approach by developing a magnetic Accordingly, Theus et al. fabricated a GelMA scaffold
bioreactor. The authors fabricated a hydrogel composed of embedded with SPIONs through a 3D printing process
two different layers: one made from glycidyl methacrylated and tested its effects on cell viability and its antibacterial
silk fibroin (Silk-GMA) with incorporated iron oxide properties. The authors concluded that the incorporation of
particles, and another made from gelatin glycidyl SPIONs in the bioink led to a decrease in the compression
methacrylate (Gel-GMA) with incorporated C2C12 cells. modulus of the hydrogel, which was attributed to the
After stimulation in the magnetic bioreactor, the authors blocking of bonds that could be formed upon crosslinking
observed that the Silk-GMA + 7% iron oxide particles within the backbone of the polymer. Cell viability was
actively responded to the magnetic force similarly until the assessed by culturing two different cell lines, HUVEC and
end of the 8-day experiment. In this assay, the myoblasts NIH3T3 (a fibroblast cell line), in the presence of SPIONs
aligned in the direction of the magnetic stretching to both in two-dimensional and 3D environments. The
which the hydrogel was exposed by two-axis and four- results showed that the hydrogel had high biocompatibility.
axis bioreactor systems. The bioreactor system promoted Furthermore, scaffolds containing SPIONs showed
the formation of multinucleated myotubes with increased enhanced antibacterial activity against Staphylococcus
myotube diameter and length, and enhanced the expression aureus, with such activity increasing with an increase in the
of myogenic markers such as Pax7, MyoG, and TnnT1. The concentration of SPIONs present in the system.

Volume 10 Issue 1 (2024) 12 https://doi.org/10.36922/ijb.0965