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International Journal of Bioprinting                         3D-printed Mg scaffolds promote bone defect repair



            degradation rate of 3D-printed Mg alloy scaffolds in vitro   we loaded ZA into the ceramic composite coating on the
            from 11.60 ± 0.05 mg/day to 2.47 ± 0.45 mg/day, which is   surface of 3D-printed Mg alloy scaffolds and promoted
            only about 21% of the original rate, greatly improving the   the healing of osteoporotic bone defects through the joint
            corrosion resistance of 3D-printed Mg alloy scaffolds. The   action of Mg ions released from the degradation of Mg
            calcium phosphate material commonly used for Mg alloy   alloy scaffolds and ZA loaded on the coating. In view of the
            surface coatings could only reduce the degradation rate of   obvious adverse effects of ZA in systemic application and
            JDBM Mg alloy bars to 72% of the original rate , and the   the small effect of the drug on local lesions [29,30] , we adopted
                                                 [22]
            protective effect of the coating on the Mg alloy substrate   the method of combining scaffold implantation with local
            was significantly weaker than that of a polysilane ceramic   drug delivery. ZA was added to the coating material to
            coating.                                           coat the surface of the scaffolds, and the drug was released
               We found that when the Mg-based implant degraded   slowly and controllably with the degradation of the scaffolds
            too quickly, a high concentration of Mg ion simultaneously   to achieve local controlled release and slow release of the
            inhibited the proliferation and differentiation of osteoblasts   drug.  In vitro drug release experiments showed that ZA
            and osteoclasts. These results are consistent with those of   was released stably from the scaffold surface at a relatively
            previous studies showing that alkaline microenvironments   low rate, and the release rate reached 54% within 30 days,
            with high Mg ion concentration as a result of Mg degradation   indicating the sustained release of the drug. When the Mg
            can  inhibit  new  bone  regeneration  and  absorption [23,24] .   alloy scaffolds were degraded, ZA loaded on the coating was
            Therefore, it is necessary to adjust the degradation rate of   released slowly and acted directly on the defect area with Mg
            Mg alloys to release an appropriate amount of Mg ions to   ions at the same time. The results showed that ZA released
            promote osteogenesis. Some studies have shown that a Mg   from the coating during degradation did not affect the effect
            ion concentration of approximately 2 mM promotes the   of Mg ions on osteogenesis, but it significantly inhibited
            proliferation and differentiation of osteoblasts in vitro and   active osteoclast differentiation and bone resorption in
            formation of new bones in vivo . The effect of osteogenic   rats with osteoporosis by inhibiting osteoclast formation,
                                     [25]
            induction is best when the concentration of Mg ions is in the   downregulating the expression levels of osteoclast-related
            range of 2.5 to 5 mM . However, when the concentration   genes and subsequently increasing bone density and bone
                             [26]
            of Mg ions is more than 10 mM, it will begin to inhibit the   strength. The results of this study suggest that combining
            osteogenic differentiation. When the concentration of Mg ion   the osteogenic effect of Mg with the inhibitory effect of ZA
            exceeds 20 mM, it will even lead to a significant increase in cell   on osteoclasts can improve the dynamic balance between
            apoptosis. The in vitro degradation experiment showed that   bone formation and resorption in the local environment
            the concentration of Mg ions produced by the 3D-printed Mg   and promote repair and reconstruction of osteoporotic
            alloy scaffolds in the ceramic coating group in the early stage   bone defects.
            of degradation was approximately 2.5 mM, and then slowly   In addition, the effect of hydrogen produced by the
            increased to 10 mM. After implantation, because of absorption   degradation of Mg alloys must be considered. Hydrogen
            in the peripheral blood circulation, the concentration of Mg   is an important degradation product of Mg. When the
            ions in the implantation area is often lower than the in vitro   degradation rate of Mg alloy implants in vivo is too rapid,
            degradation concentration in the same period . Therefore,   the hydrogen produced cannot be absorbed by the body
                                                [27]
            it can be speculated that ceramic-coated Mg alloy scaffolds   in time and accumulates in the implanted area to form a
            implanted into the body form a microenvironment in which   subcutaneous cavity. The rapid accumulation of hydrogen
            the concentration of Mg ions is less than 10 mM, which is   delays bone healing, forms obvious tissue calluses, blocks
            conducive to osteogenic differentiation. The released Mg   blood flow, and leads to tissue necrosis . Therefore, it is
                                                                                               [31]
            ions can upregulate expression of osteogenic-related genes,   necessary to adjust the degradation rate of Mg alloys to
            promote the proliferation and differentiation of osteoblasts,   reduce hydrogen production. Although a large amount
            and accelerate the growth of new bone in the bone defect.   of hydrogen has adverse effects on patients, hydrogen,
            The future research goal is to achieve a precise match between   as an important pathophysiological regulator, has great
            the scaffold degradation rate and the bone growth rate by   potential to regulate oxidative stress, inflammation, and
            adjusting the coating thickness, which will lead to complete   apoptosis . Hydrogen not only reduces oxidative stress by
                                                                      [32]
            repair of the defect when the scaffold is completely degraded.  directly reacting with strong oxidants, but also indirectly
               The number of BMSCs involved in bone repair and   reduces oxidative stress by regulating the expression of
            their differentiated osteoblasts in patients with osteoporotic   various genes . In this study, the detection of ROS in
                                                                          [33]
            bone defects decreased, and their function was low, while   osteoclasts showed that the average fluorescence intensity
            the osteoclasts were abnormally active, resulting in slow   of ROS in the Mg alloy group was significantly lower
            rate and prolonged time of defect repair . Based on this,   than that in the control group, demonstrating that the
                                            [28]

            Volume 9 Issue 5 (2023)                        414                         https://doi.org/10.18063/ijb.769
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