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




            ZIF-8 nanoparticle concentration. In vivo experiments proved that the scaffolds eliminated infection and promoted
            new bone formation in infected bone defect. Given excellent osteogenic and antibacterial activities, the 3D-printed
            PCL/Fe O @ZIF-8 nanocomposite scaffolds could serve as novel materials for the treatment of infected bone defects.
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            Keywords: Infected bone defect; 3D printing; Fe O  nanoparticles; Zinc-based imidazole zeolite framework-8; Anti-
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            bacterial activity; Bone regeneration

            1. Introduction                                    surface area, and high thermal stability. The sustained
                                                               release of zinc ion during the degradation of ZIF-8, which
            Treatment of large-scale bone defects caused by trauma   acts as an excellent zinc ion reservoir, possesses efficient
            or  tumor  excision  remains  a  growing  clinical  challenge   bactericidal activity and promotes osteoblast proliferation
            nowadays.  Currently, the usage of standard clinical   and differentiation. 16,17  Therefore, ZIF-8 was expected
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            treatments, including autologous and allogeneic bone graft   to be a promising antibacterial and osteogenic material.
            transplantation, was limited, due to the shortcomings such   Many studies combined ZIF-8 with other biomaterials
            as deficient supply, donor sites complications, potential   to fabricate multifunctional scaffold, which could inhibit
            immune rejection, and so on. In recent years, an increasing   bacterial growth and promote wound vascularization and
            number of synthetic biomaterials have been extensively   osteogenesis, thereby accelerating bone reconstruction
            used as bone substitutes to repair bone defects.  However,   and infected wound healing. 18-20  Fe O and ZIF-8 have
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            bone defects and implanted biomaterials, throughout   been combined to fabricate Fe O @ZIF-8 nanocomposites,
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            their service life, are vulnerable to infection. Infection can   which were mainly used as catalysts, to remediate copper
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            hinder bone recovery and new bone formation, inevitably   and arsenic contaminated water and soil, and to monitor
            resulting in the failure of bone defects treatment with   environmental chemicals. 21-26  These applications provide
            biomaterials.   Effective  biomaterials  that  can  be  used  to   an explanation regarding the extensive usage of Fe O @
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            repair bone defects in infected areas are lacking. Thus,   ZIF-8 nanoparticles in livestock husbandry, agriculture,
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            it is imperative to develop bone substitute biomaterials   and environmental detection and protection. The
            with  dual  functionality  of  bacterial  inhibition  and  bone   treatment effects of Fe O @ZIF-8 nanoparticles in human
            regeneration to treat infected bone defects.                         3  4
                                                               diseases  have  not  been  clearly  investigated.  Previous
               Magnetic  Fe O 4  nanoparticles  have  excellent  studies further found crystal structures of Fe O  and
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            superparamagnetism, good biocompatibility, and nanometric   ZIF-8 in Fe O @ZIF-8 nanocomposites,  indicating that
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            sizes,  promoting their extensive usage in biomedicine field,   the nanocomposites may harbor the properties of both
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            with applications in cancer hyperthermia, drug delivery, and   Fe O  and ZIF-8. Nevertheless, the bone regeneration and
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            anemia. In recent years, Fe O  nanoparticles also have been   antibacterial functions of Fe O @ZIF-8 remain obscure,
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            proved to be promising materials  for bone regeneration.   and the treatment effects of Fe O @ZIF-8 nanocomposites
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            Numerous studies found that Fe O  nanoparticles can   on infected bone defects have yet to be clarified.
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            improve proliferation and differentiation of stem cells and   Selecting an appropriate technique to manufacture
            osteoblasts, and the micro-magnetic fields generated by   Fe O @ZIF-8 nanocomposites is an important facet to
            Fe O  nanoparticles attract and promote adherence of stem   generate scaffolds that best fit the bone defect. Three-
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            cells, living growth factors, and  other bioactive agents,   dimensional printing technique is an ideal technology
            thereby promoting bone regeneration. 8-12  Moreover, Fe O    to  fabricate  customized bone  substitute scaffolds that
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            nanoparticles can serve as composite with other osteogenic   perfectly fit bone defects. 28,29  Furthermore, 3D printing
            materials, such as polycaprolactone (PCL) and mesoporous   could effectively control the pore interconnection, pore
            bioactive glass (MBG), delivering remarkable reparative   size, and overall porosity of biomaterials to fabricate
            effects on bone defects in vivo. 13,14  However, the antibacterial   3D  porous scaffolds. 30,31  3D  porous  scaffolds provided a
            effect and bone regeneration ability of Fe O  nanoparticles in   favorable  microenvironment  for  cell  adhesion,  growth,
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            infected areas have yet to be clarified. For infected wounds,   and phenotype maintenance, which is beneficial for bone
            Fe O nanoparticles were always composite with antibiotic   regeneration. Moreover, 3D printing could combine
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            or antibacterial materials, such as minocycline and silver   different materials with different functions to fabricate
            nanoparticles.
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                                                               multifunctional  therapeutic  systems.  Polycaprolactone
               Zinc-based zeolitic imidazolate framework-8 (ZIF-  (PCL) is an aliphatic polyester that is widely used in bone
            8) is a type of metal organic frameworks (MOFs), with   tissue engineering.  The tunable physicochemical and
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            intersecting three-dimensional (3D) structure, large specific   mechanical properties of PCL make it a good material
            Volume 10 Issue 4 (2024)                       298                                doi: 10.36922/ijb.2271
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