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

ZIF-8 group than those in the control group and PCL group weeks (Figure 8A). In addition, quantitative micro-CT
(Figure 6B–F). The increased expression of these proteins analysis showed that the BV/TV and Tb.N values in the
was also effectively inhibited by adding DKK1 (Figure 6B–F). PCL/10% Fe O @ZIF-8 group were significantly higher
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These findings demonstrated that the Wnt/β-catenin than those in the PCL group and the control group, at both
signaling pathway was related to the osteogenic effect of time points (Figure 8B and C). These results suggested
the PCL/Fe O @ZIF-8 scaffolds on BMSCs. that PCL/10%Fe O @ZIF-8 scaffolds successfully repaired
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critical-size bone defects in the infected condition.
3.7. Effects of PCL/Fe O @ZIF-8 scaffolds on
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antibacterial activity and bone defect repair in vivo Furthermore, Masson’s trichrome and H&E staining
As illustrated in Figure 7A, the scaffolds were soaked in were used to histologically investigate the effects of scaffolds
bacterial suspension and then embedded in subcutaneous on bone regeneration. After 6 weeks of implantation, the
tissue or cranial critical defect, to evaluate the antibacterial defect area in the PCL group was mainly filled with fibrous
activity in vivo. After 3 days of subcutaneous embedding, tissue without obvious new bone formation, while new
the pus exudation became visually more obvious in PCL bone and fibrous tissue appeared in the PCL/10%Fe O @
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group, compared with the PCL/10%Fe O @ZIF-8 group ZIF-8 group (Figure 8D and E). After 12 weeks of
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(Figure S4A in Supplementary File). Meanwhile, H&E implantation, most of the defects in PCL/10%Fe O @ZIF-
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staining and Giemsa staining of tissue around the scaffolds 8 group were bridged by mature or engineered bone tissue
showed that there were less inflammatory cells (Figure 7B, (Figure 8D and E). At both time points, the collagen fiber
green arrows) and less bacteria (Figure 7B, red arrows) in the mineralization degree in PCL/10%Fe O @ZIF-8 group
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PCL/10%Fe O @ZIF-8 group than in the PCL group. After was higher than that in the other groups, indicating that
Fe O @ZIF-8 nanoparticles contribute to osteogenesis
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7 days of cranial defect implantation, more pus was seen on and mineralization. These results indicated that PCL/10%
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the removed PCL scaffold compared to PCL/10%Fe O @ Fe O @ZIF-8 scaffolds effectively promoted mineralized
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ZIF-8 scaffold (Figure S4B in Supplementary File). Micro- new bone formation in the critical-size bone defect under
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CT images showed that the cranial defects outline was less infected environment. The immunofluorescence staining
smooth in PCL and PCL/10% Fe O @ZIF-8 groups than results showed that the expression of β-catenin and RUNX2
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in the control group (Figure 7C). There were less uneven were significantly increased in PCL/10%Fe O @ZIF-8
etched concaves on the defect edges and the cranial surfaces group, compared to that in control group and PCL group
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in the PCL/10%Fe O @ZIF-8 group, compared with those (Figure 9), a finding aligned with the expression profile of
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in the PCL group (Figure 7C, blue arrows), indicating Wnt/β-catenin pathway proteins in BMSCs treated with
that bacterial erosion and bone loss were inhibited by PCL/Fe O @ZIF-8 scaffolds in vitro.
PCL/10%Fe O @ZIF-8 scaffold. Moreover, CFU counts 3 4
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were significantly lower in the PCL/10%Fe O @ZIF-8 4. Discussion
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group than those in the PCL group (Figure 7D and E).
The gene expression levels of inflammatory cytokines, The treatment of infected bone defects remains challenging
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including IL-6 and TNF-α, were significantly lower in the in clinical settings. Therefore, novel biomaterials for bone
PCL/10%Fe O @ZIF-8 group than that in the PCL group regeneration and infection control are urgently needed.
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(Figure 7F and G). These results indicated that Fe O @ZIF- The traditional antibiotic-carrying scaffolds reduce
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8 nanoparticles had high antibacterial activities in vivo. bacterial infection, but the emergency of drug-resistant
bacteria has significantly limited their application.
To evaluate the ability of PCL/10%Fe O @ZIF-8 Additional compounds are also required to confer
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scaffold in promoting bone regeneration under infectious scaffolds with osteogenic properties. 42,43 Thus, scaffold
microenvironment, the skull bones were collected and systems that can simultaneously reduce bacterial infection
detected by micro-CT and histologic means, after 6 and and promote osteogenesis need to be developed. In the
12 weeks of infected scaffolds implantation in cranial present study, we successfully fabricated magnetic PCL/
critical-size defect. As shown in Figure 8A, micro-CT Fe O @ZIF-8 scaffolds through 3D printing method. The
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images showed that the PCL/10%Fe O @ZIF-8 scaffold scaffolds possessed good biocompatibility and promoted
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significantly enhanced new bone formation and growth the proliferation, adhesion, and osteogenic differentiation
compared to the PCL group and the control group. of BMSCs. The antibacterial effects were increased with
Interestingly, significant marginal bone resorption was concentration of Fe O @ZIF-8 magnetic nanoparticles,
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seen after 6 and 12 weeks of PCL scaffold implantation, and PCL/10%Fe O @ZIF-8 had the best osteogenic
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while slight marginal bone resorption occurred after 6 ability, which might be related to the activation of Wnt/
weeks of PCL/10%Fe O @ZIF-8 scaffold implantation, β-catenin signaling pathway. PCL/10% Fe O @ZIF-8
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and new bone filled most of the defective areas after 12 scaffolds successfully inhibited the bacterial activity and
Volume 10 Issue 4 (2024) 310 doi: 10.36922/ijb.2271