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3D Printed and Ion Controllable Release

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           Figure 8. The expression of osteogenesis-related genes of mBMSCs grown on the poly-Llactic acid (PLLA) and 4 zinc-doped mesoporous
           silica/PLLA scaffolds after being cultured for 7 and 14 days.

           expression of RUNX2,  COL-I, OCN, and OPN.  With    proliferation of stem cells . In this study, the 4Zn-MS/
                                                                                     [48]
           an increase of culture time to 14 days, the expression of   PLLA composite scaffold sustainedly released Zn ions in
           RUNX2 and COL-I genes was further upregulated, and   a low range (0.18 – 0.5 mg/L) and Si ions in a moderate
           the expression of RUNX2 and COL-I genes of mBMSCs   range (31 – 43 mg/L), reducing the potential cytotoxicity
           grown on the 4Zn-MS/PLLA sample was higher than that   of these metal  ions. Therefore, the synthesized Zn-MS
           on the PLLA scaffold. These results showed that Zn-MS   particles could effectively improve osteogenic activity of
           particles significantly improved the osteogenic activity of   the PLLA scaffold.
           PLLA scaffold.
               Many studies demonstrated that Zn ions displayed   4 Conclusions
           promoting  effects  on  osteogenesis.  The  proper  Zn  ion   MS particles  (Zn-MS) with  rosette-like  morphology
           concentration  could improve  the adhesion and spread   and  uniform  mesoporous  structure  were  successfully
           of stem cells by upregulating the expression of integrin.   synthesized by one-pot hydrothermal  method.  Then,
           Meanwhile,  Zn ions also penetrate  into cytoplasm  by   the PLLA composite scaffolds with different amount of
           zinc (Zn) transporter (ZIP1 and ZnT1), thus moderately   Zn-MS were prepared by SLS technique. All composite
           increasing  concentration  of intracellular  Zn ions.  The   scaffolds were able to sustainedly release Zn and Si
           enhancement  of Zn ion concentration  in cells further   ions. The addition of 4 wt.% Zn-MS not only evidently
           activates MAPK/ERK signaling pathway and upregulates   increased the compressive strength of the PLLA scaffold
           the expression of osteogenesis-related genes. However,
           high Zn ion concentration  (15 mg/L) leads to over-  but also obviously improved the osteogenic activity of the
           expression of Zn transporter, which makes excessive   PLLA scaffold. Considering their favorable morphology
           Zn ions inflow into cytoplasm. And then, the production   and sustainedly release active ions, the Zn-MS particles
           of reactive  oxygen species  (ROS) increases,  thereby   showed  tremendous potential  to improve mechanical
           resulting in cell apoptosis . In addition, Si ions are   properties  and osteogenic  activity  of various polymer
                                  [46]
           also essential  to bone growth . It was reported that   scaffolds.
                                     [47]
           Si  ions  significantly  improved  the  proliferation  and   Acknowledgments
           osteogenic differentiation of stem cells with involvement
           of  WNT and SHH signaling pathway. However, high    This study was supported by the  following  funds:
           Si ion concentration  (140 mg/L) could suppress the   (1) The Natural Science Foundation of China (51935014,

           100                         International Journal of Bioprinting (2021)–Volume 7, Issue 2
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