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

nuclei. At this stage, all the precursors added are consumed in a sealed container and kept at high temperature—
in particle growth, and no new nuclei are formed, as long 130–250°C—and high pressure—0.3–4 MPa. Finally, the
as the rate of precursor reaction with the existing nuclei is solution is filtered, and the solid components are dried and
higher than the rate of formation of new nuclei particles. lyophilized, leading to the final product. 31
30
By controlling the rate of addition of precursors, it is This type of processing provides many advantages,
possible to control the MNPs size distribution, achieving such as the tailored MNPs morphology, which can present
populations with low polydispersity indices. the shape of nanorods, nanotubes, nanosheets, and
31
Several strategies for the formulation of MNPs have nanorings. Moreover, the fabrication also allows to obtain
been explored in the past few years in order to obtain MNPs a highly organized crystallite structure and does not employ
with the desired features such as shape, size, magnetic organic solvents. However, this strategy is time-consuming
36
controllability, and biocompatibility. These particles can due to its slow kinetics. Hydrothermal methods have been
be synthesized using physical and chemical methods, with used to fabricate magnetic nanoparticles for use in several
6
some of the most reported ones being co-precipitation, biomedical applications, such as muscle and cartilage 37
thermal decomposition, and hydrothermal method. tissue engineering.
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Examples of these strategies are summarized in Table 1.
2.3. Thermal decomposition
2.1. Co-precipitation Formation of MNPs by thermal decomposition starts with
Co-precipitation is the most popular method to fabricate iron precursors being decomposed in high-temperature
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MNPs, since it is very straightforward and does not involve organic solvents, with surfactant stabilizers in order
39
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harmful precursors as in other fabrication methods. to prevent the agglomeration of the formulated MNPs
Generally, it requires the dissolution of iron salts, with ferrous (Figure 1C). This decomposition can happen following two
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and ferric ions, which are then added to a basic solution processes: heating-up and hot-injection. In the heating-
at high or room temperature, causing the precipitation of up method, the pre-mixed precursor reagents, solvent, and
the MNPs through a quasi-immediate crystallization that surfactant stabilizers are heated to a certain temperature
is greatly dependent on the electron exchange between Fe range. Temperatures in the range of 100–350°C have
3+
and Fe (Figure 1A). The size and shape of the obtained been shown to promote the formation of monodisperse
2+
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particles depend greatly on various factors, such as pH, particles with sizes between 4 nm and 30 nm.
ionic ratio, temperature, type of salts used, and rate at which In the hot-injection method, the growth phase is
the solutions are mixed, among others. Furthermore, the controlled by injecting the reagents into the hot
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39
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composition of the particles, whether they are composed surfactant solution, causing burst nucleation. Particles
of Fe O , Fe O , or other iron oxides, also depends on the synthesized using the thermal decomposition method
2
4
3
3
environmental conditions mentioned above. have been used in several biomedical applications,
namely tumor ablation. 9
This method, however, presents some limitations, such
as the agglomeration of the nanoparticles during their Besides the option of synthesizing these particles in-
fabrication, the need for careful control of the experimental house, MNPs are also commercially available, simplifying
factors of the reaction, such as temperature and pH, and the process for the formulation of magnetic bioinks.
the difficulties in creating a monodisperse and uniform These MNPs have been subjected to extensive quality
population of MNPs. This issue can be addressed through control procedures, providing better reassurance of their
21
the functionalization of the formed particles, either by ligand performance in the desired applications. Some of the
addition/exchange or through particle encapsulation. commercially available options are listed in Table S1
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MNPs formulated by the co-precipitation method have (Supplementary File).
been used in several areas of tissue engineering, namely
for bone and neural regeneration strategies, anticancer 3. Incorporation of MNPs in hydrogels
8,25
7
hyperthermia therapies, 34,35 controlled drug release Magnetic hydrogels have been increasingly used in many
systems, and providing antimicrobial properties. 24 fields of study due to their unique characteristics. MNPs
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can be incorporated into the hydrogels through three main
2.2. Hydrothermal method methods: blending, grafting-onto method, and in situ
The hydrothermal method (Figure 1B) is also another precipitation. These are summarized in Table 2.
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commonly used strategy for the fabrication of MNPs.
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As described previously, metal salts are dissolved in water, 3.1. Blending method
which is followed by the addition of a basic solution until The blending method is the most commonly used
an alkaline pH is reached. Afterward, the mixture is placed method for the incorporation of MNPs into a hydrogel
Volume 10 Issue 1 (2024) 3 https://doi.org/10.36922/ijb.0965