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International Journal of Bioprinting                         3D printing of smart constructs for precise medicine


            through engineered tissues and tissue-like constructs ,   highlights  the  variability  in  the  selection  of  biomaterial
                                                        [82]
            allowing for the in situ manipulation of materials and cells.   inks for precision medicine.
            Ultrasound can be employed with high biocompatibility
            by managing the duration and intensity of the stimulating   3.6. Magnetic stimulation
            ultrasound [104] . Therefore, the design of tissue structures   Magnetically  responsive  biomaterials  have  been
            capable of cellular control using ultrasound stimuli   introduced into  biomedicine to  improve the  biological
            is a promising area in the field of tissue engineering   activity of cells, tissues, and organs [109] . This is mainly
            approaches.                                        due to their responsiveness to external magnetic fields.
              One   strategy  to  create  ultrasound-responsive  This stimulation remotely regulates the biochemical and
            biomaterial inks involves incorporating acoustic-  physical-mechanical properties toward native tissues
                                                                        [109]
            responsive delivery particles into the biomaterial ink.   and organs  . Several outcomes have demonstrated that
            The sustained delivery of certain growth factors might   magnetic biomaterial inks can function as superior drug
                                                                                                 [11]
                                                        [82]
            benefit effective tissue regeneration [105] . Kennedy et al.    release  and  targeted  systems.  Gao  et al.  developed  a
            demonstrated that ultrasound-burstable capsules with   magnetic biomaterial ink based on ferromagnetic vertex
            high retention could be integrated into bulk biomaterial   domain iron oxide. The result demonstrated that the
            inks for controlled release. Alginate-based capsules   developed magnetic ink could remarkably suppress the
            with a 4  mm diameter were formulated for loading the   local recurrence of breast tumors. In addition, Manjua
                                                                    [110]
            nanoparticle-based payload solutions. The formulated   et  al.   developed a magnetically responsive PVA
            alginate capsules showed near-complete retention of the   hydrogel that could be activated by an on/off magnetic
            gold nanoparticle (AuNP) payload for 7 days. The ability to   field to regulate motility and sorption non-invasively. This
            rupture weak capsules with lower-intensity ultrasound was   magnetism-based biomaterial can be used as a promising
                                                                                                       prepared
                                                                                                   [111]
                                                               drug delivery system or biosensor. Chen et al.
            evaluated while ensuring sustained release from stronger   a novel magnetic biomaterial ink by combining self-
            walled capsules. AuNPs were further modified with BMP2
            to better induce osteogenic differentiation.       healing chitosan/alginate biomaterial inks with magnetic
                                                               gelatin microspheres.
              Ultrasound stimulation can be employed to control
            crosslinks within a biomaterial ink, which can influence   Most studies on this topic have evaluated magnetic
            the release profile [106,107] . As an example, Huebsch et al. [106]    nanoparticle (MNP) incorporated hydrogels for bone
                                                                         [112]
            addressed this issue by formulating an ionically cross-linked   regeneration  . Since hydroxyapatite (HAP) is the well-
                                                               qualified  inorganic  component  of  native  bone  tissue,  a
            alginate biomaterial ink to which ultrasound exposure   magnetic HAP composite biomaterial ink was fabricated
            could increase the drug release rate, facilitating repeated   for enhanced bone tissue regeneration. Specifically,
            release. Ultrasound stimulation enables the degradation of   nano-HAP-coated  γ-Fe O   nanoparticles  (m-nHAPs)
            the guluronic acid chains of alginate polymers, increasing   were formulated and then added into a PVA solution.
                                                                                     3
                                                                                   2
            the payload release. When the ultrasound was completed,   As a result, PVA exhibits excellent biocompatibility, slow
            the crosslinks were reformed through the calcium binding.   biodegradation, and excellent mechanical properties,
            It eventually reduces the release rate. Furthermore, they   which are essential for personalized application. The pore
            exhibited the pulse release of ECM-binding cytokine   sizes of the hydrogels gradually increased, followed by
            and stromal cell-derived factor-1. Biomaterial inks that   an increase in  m-nHAP content. The proliferation and
            allow ultrasound-induced growth factor release provide a   function of human osteoblasts were significantly enhanced
            method for personalized remote control of bioactive cues   when the concentration of m-nHAP increased. Zhang
            from engineered constructs, which can lead to optimal   et al.  also studied magnetic biomaterial ink for enhanced
                                                                   [16]
            tissue regeneration depending on the bodily conditions of   cartilage tissue engineering. In this study, PVA-conjugated
            patients.                                          Fe O  MNPs were prepared using the grafting-on method.
                                                                   4
                                                                 3
              In addition to photothermal-activated biomaterial   Subsequently, it was mixed with a hybrid biomaterial ink
            inks, ultrasound-activated reactions are unique candidates   (MagGel) composed of PEG, HA, and type II collagen using
            of biomaterial ink sources for precision medicine.   a mechanical method. The in vitro results showed that the
            Specifically, ultrasound can be used as an energy source   MagGel lost its structural integrity after incubation at 37°C
            to control a fabricated construct remotely. Habibi et al. [108]    for 21 days. The findings demonstrated that the magnetic
            demonstrated the 3D printing of structures using acoustic   nanocomposite biomaterial ink had a microstructure and
            cavitation through the concentrated ultrasound and   chemical components similar to those of natural hyaline
            showed its potential by printing ear and nose constructs.   cartilage and supported bone mesenchymal stem cell
            This finding based on ultrasound-activated reactions   behavior in vitro.


            Volume 9 Issue 1 (2023)                        241                      https://doi.org/10.18063/ijb.v9i1.638
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