Page 322 - IJB-10-4
P. 322

International Journal of Bioprinting                              PCL/Fe3O4@ZIF-8 for infected bone repair




            charged bacteria, causing the collapse and disruption   pathways and promotes the proliferation and differentiation
            of bacterial cell membranes.  Furthermore, Zn could   of osteoblasts.  Li et al. showed that the construction of a
                                                    2+
                                                                          58
                                    17
            enter bacterial cells, break enzymes, and react with DNA   magnetic microenvironment by adding Fe O nanoparticles
                                                                                                  4
                                                                                                3
            to kill the bacteria. After killing a bacterium, Zn  would   to poly (lactic-co-glycolic acid)/hydroxyapatite (PLGA/
                                                   2+
            be released and move on to kill another bacterium, in a   HAP) scaffolds can significantly promote the formation
            bactericidal chain that results in long-lasting antibacterial   of new bone tissue  in vivo.  In general, the earth has a
                                                                                     59
            effects. 16-17  Another study showed that ZIF-8 could   natural magnetic field, and the geomagnetic field has
            trigger the inhibition of arginine biosynthesis pathway   good biological effects on a wide range of organisms, from
            and the production of ROS, which lead to dysfunctional   single-celled organisms to mammals.  To a certain extent,
                                                                                            60
            tricarboxylic acid cycle and disruption of cell membrane   compared with external magnetic fields, the geomagnetic
            integrity, eventually killing methicillin-resistant S. aureus   field provides a safer and more reliable magnetic effect on
            (MRSA) isolates.  In the current study, we found that   organisms.  Based on previous studies and our findings,
                          46
                                                                       61
            Zn  ions were slowly released from the PCL/Fe O @ZIF-  we estimated that the bone regeneration mechanism maybe
              2+
                                                  3
                                                     4
            8 scaffolds for more than 7 days. According to published   related to the Fe O  nanoparticles and superparamagnetism
                                                                             4
                                                                           3
            literature and our  findings, we postulated a potential   in PCL/Fe O @ZIF-8 scaffolds. However, the present study
                                                                         4
                                                                       3
            connection between the antibacterial mechanism of   showed that the loading of Fe O  into ZIF-8 host was
                                                                                         3
                                                                                           4
            PCL/Fe O @ZIF-8 scaffolds and the sustained release   estimated to be 13.1% in the nanoparticles; therefore, the
                  3
                    4
            of functional Zn . However, Fe O  nanoparticles were   role of ZIF-8 and Zn  in bone regeneration should not be
                                                                               2+
                          2+
                                         4
                                       3
            reported  to  exhibit  an  efficient  role  in  the  dispersal  and   neglected. Some studies attributed the bone regeneration
            removal of bacterial biofilms by generating free radicals   effects of ZIF-8-modified composites to the sustained
            and then disrupting the microenvironments.  Further   release of Zn , which played regulatory role in promoting
                                                  47
                                                                         2+
            studies are warranted to explore the more specific   the growth and maturation of bone tissue, and effectively
            mechanisms underlying the antibacterial activity of   improved the osteogenic function of related cells. 16,44
            PCL/Fe O @ZIF-8 scaffolds.
                  3  4                                            In the present study, we found that PCL/5%Fe O @
                                                                                                         3
                                                                                                           4
               Bone regeneration and remodeling is a complex   ZIF-8 and PCL/10%Fe O @ZIF-8 significantly promoted
                                                                                 3
                                                                                    4
            process that requires a stable internal environment and   the proliferation and adhesion of BMSCs. In addition,
            the coordination of multiple cells.  In the present study,   the PCL/Fe O @ZIF-8 scaffolds significantly upregulated
                                       18
                                                                          4
                                                                        3
            PCL/Fe O @ZIF-8 scaffolds successfully repaired the   the  expression  of  osteogenesis-related  genes,  including
                    4
                  3
            critical-size cranial defects. In animal studies, micro-  Alp,  Runx2,  Col-1, and  Ocn in osteoblasts. Studies
            CT showed the conspicuous formation of several new   have  shown  that  Alp  and  Runx2  play  key  roles  in  early
            bones in PCL/10%Fe O @ZIF-8 after 6 and 12 weeks of   osteogenic differentiation.  Moreover,  Col-1 and  Ocn
                                                                                    62
                             3
                               4
            implantation. Histological analysis through H&E and   are  essential  in  deposition  and  mineralization  of  bone
            Masson’s trichrome staining showed that PCL/10%Fe O @  in the late stage of osteogenesis.  Taken together, we
                                                                                           63
                                                      3
                                                        4
            ZIF-8 promoted new bone formation in the early stage and   estimate that PCL/Fe3O4@ZIF-8 scaffolds stimulate bone
            bone tissue integration in the scaffold in the later stage.   regeneration by promoting adherent BMSCs proliferation,
            Wu et al.  showed that a low dose of Fe O  nanoparticles   osteogenic differentiation, and mineralization through
                   48
                                              4
                                            3
            (50 µg/mL) significantly promoted the proliferation and   upregulating osteogenesis-related gene expression. The
            cell viability of BMSCs. Fe O  nanoparticles have a great   Wnt/β-catenin signaling pathway plays a prominent
                                    4
                                  3
            application potential in bone tissue engineering because   role in bone metabolism, which is closely related to the
            they can promote osteogenesis and angiogenesis 49-51  with or   proliferation, differentiation, and function of BMSCs
            without an external magnetic field. 52-55  Fe O  nanoparticles   and osteoblasts. Modulation of Wnt/β-catenin signaling
                                              4
                                            3
            produced and converted the continuous weak magnetic   pathway is a widely used approach to the treatment of
            force acting on cells into intracellular biochemical signals,   various osteolytic osteopathies.  The secreted Wnt ligands
                                                                                        64
            which possibly promoted bone regeneration. 33,53,55,56  The   bind to transmembrane receptors Frizzled and lipoprotein
            PCL/Fe O @ZIF-8 scaffolds showed superparamagnetism   receptor-associated protein (LRP5) and/or LRP6 to initiate
                    4
                  3
            and high saturation magnetization in our study. Previous   receptor activation and signal transduction, thereby
            studies 12,57  have indicated that the superparamagnetism and   activating the Wnt/β-catenin signaling pathway. The key
            high saturation magnetization of the scaffolds are expected   molecule, β-catenin, is released from the complex of colonic
            to enhance the magnetic stimulation of the cells growing on   adenomatous  polyposis  coli, GSK-3β,  and  Axin,  which
            them. The magnetic stimulation effect is mainly based on the   improves its accumulation in the nucleus and subsequently
            nano-scale magnetic microenvironment provided by Fe O    induces the expression of cell-related osteogenesis-
                                                        3
                                                          4
            nanoparticles, which activates various cellular signaling   related  genes.   In  the  present  study,  PCL/Fe O @ZIF-8
                                                                          65
                                                                                                     3  4
            Volume 10 Issue 4 (2024)                       314                                doi: 10.36922/ijb.2271
   317   318   319   320   321   322   323   324   325   326   327