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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
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enter bacterial cells, break enzymes, and react with DNA magnetic microenvironment by adding Fe O nanoparticles
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to kill the bacteria. After killing a bacterium, Zn would to poly (lactic-co-glycolic acid)/hydroxyapatite (PLGA/
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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
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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,
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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,
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Zn ions were slowly released from the PCL/Fe O @ZIF- we estimated that the bone regeneration mechanism maybe
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8 scaffolds for more than 7 days. According to published related to the Fe O nanoparticles and superparamagnetism
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literature and our findings, we postulated a potential in PCL/Fe O @ZIF-8 scaffolds. However, the present study
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connection between the antibacterial mechanism of showed that the loading of Fe O into ZIF-8 host was
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PCL/Fe O @ZIF-8 scaffolds and the sustained release estimated to be 13.1% in the nanoparticles; therefore, the
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of functional Zn . However, Fe O nanoparticles were role of ZIF-8 and Zn in bone regeneration should not be
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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
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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 @
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Bone regeneration and remodeling is a complex ZIF-8 and PCL/10%Fe O @ZIF-8 significantly promoted
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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
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PCL/Fe O @ZIF-8 scaffolds successfully repaired the the expression of osteogenesis-related genes, including
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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
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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
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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
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(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
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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
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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
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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
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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-
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nanoparticles, which activates various cellular signaling related genes. In the present study, PCL/Fe O @ZIF-8
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Volume 10 Issue 4 (2024) 314 doi: 10.36922/ijb.2271

