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




               In a study targeting neural tissue engineering,   agents and in tumor ablation strategies. Moreover, it
            Ghaderinejad  et al. developed an alginate hydrogel   is expected that magnetic hydrogels will be employed
            containing magnetic short polycaprolactone (PCL)   as smart advanced biosystems in emerging fields such
            nanofibers (MSNFs) aiming to induce neuronal       as soft robotics. Furthermore, 3D (bio)printing of
            differentiation in olfactory ectomesenchymal stem cells   these stimuli-responsive materials will allow for the
            (OE-MSCs).  The MSNFs were proven to be orientable   scalable and reproducible fabrication of constructs with
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            by an external magnetic field within the magnetic   complex structures able to mimic the properties of the
            hydrogel,  as  in  the  previous  study,  and  the  storage   native tissues and to be externally stimulated to foster
            modulus of the bioink was found to be in the range of   regenerative processes. Additionally, the incorporation
            the values reported for the brain tissue (100–1000 Pa).     of magnetic particles into hydrogels also allows a better
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            Additionally, the results showed that the hydrogels   modulation of the hydrogels’ features, since an external
            containing MSNFs were able to promote the OE-MSCs   magnetic field can control the positioning of the MNPs
            neuronal differentiation.                          within the scaffold, conferring different properties
                                                               to different locations of the scaffold, which might
               Another biomedical application of magnetic hydrogels   contribute to the recapitulation of highly heterogeneous
            is their use in hyperthermia anticancer therapies. This   tissues.
            type of therapy takes advantage of an external alternating
            magnetic field to stimulate the magnetic nanoparticles   However, there are still some issues that need to be
            present within the hydrogel. When this stimulus is applied,   further optimized for their effective implementation.
            the  MNPs  dissipate  heat  through  relaxation  losses  and   Regarding the use of 3D-(bio)printed magnetic hydrogels
            hysteresis,  and  this  heat  then  causes  the  death  of  the   for tissue engineering applications, there have been
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            surrounding cancer cells.  Given that this heat release can   conflicting reports concerning the effect of the introduction
            cause unwanted damage to cells neighboring the tumor, it   of MNPs within the hydrogel matrix. Some studies have
            is crucial for the hydrogel to be accurately injected into the   reported the improvement of mechanical properties,
            desired location. For this purpose, Qian et al. constructed   which translate to increased stiffness and higher Young’s
            an injectable silk fibroin hydrogel (FSH) with confined   modulus, due to the interaction of these particles with the
            polyethylene glycol stabilized hydrophilic iron oxide   polymer chains. However, other works claimed that the
            nanocubes (IONCs) and evaluated its effectiveness in the   introduction of MNPs disturbs the bonds between chains
            targeting and ablation of tumors.  The scaffolds showed   within the hydrogel, thus decreasing their mechanical
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            good injectability and a quick response to an external   performance. Therefore, further research is needed to
            magnetic field. Furthermore, its self-healing behavior was   define, more specifically, how these particles interact with
            tested and proven, which is crucial for the recovery of the   their surrounding matrix, in order to accurately tune the
            gel state following injection. Finally, after implantation in   scaffolds features.
            mouse and rabbit models,  its hyperthermic effects were   MNPs—more specifically magnetite and maghemite—
            observed.                                          have been shown to be cytocompatible in several in vitro
                                                               and  in vivo  animal studies. Nevertheless, given that the
               Extensive research has been made regarding the
            injectability of hydrogels and its applicability in several   human body consists of several complex systems whose
                                                               interaction is not accurately represented by these models,
            domains of research. 86,87  Besides its applications in the   it is crucial that magnetic hydrogels can be tested in more
            local delivery of hydrogels in a highly precise manner and   advanced in vitro humanized models and in clinical trials in
            through non-invasive methods,  we reckon that the results   order to move toward the final goal of their implementation
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            of these works can show whether a bioink formulation   into clinical practice.
            possesses the  right mechanical and  rheological features
            to manufacture a solid 3D structure via a 3D (bio)    Finally, 3D (bio)printing of cell-laden bioinks has not
            printing process. This demonstrates the current potential   been very extensively explored. The incorporation of cells
            of injectable magnetic hydrogels and its potential to be   in the bioink allows for a more uniform dispersion of cells
            applied in 3D (bio)printing approaches.            within the hydrogel while still allowing the precise definition
                                                               of its shape and structure. Nonetheless, these magnetic
            6. Conclusion and future perspectives              bioinks must have characteristics that are compatible with

            With a broad spectrum of applications, magnetic    cell viability—such as a shear-thinning behavior.
            hydrogels are used not only in several branches of tissue   Overall, we envision that  magnetically-responsive
            engineering, for example, neural, muscle, cartilage,   systems will have a great impact on tissue and organ
            and bone tissue regeneration, but also as antibacterial   engineering due to their unique characteristics that allow


            Volume 10 Issue 1 (2024)                        14                         https://doi.org/10.36922/ijb.0965
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