Treatment effects of 3D-printed PCL/Fe3O4@ ZIF-8 magnetic nanocomposite on infected bone defect

 Treatment of large bone defects remains a clinical challenge, especially for defects compounded by infection. It is essential to develop dual functional therapeutic systems that inhibit bacterial growth and promote bone regeneration for infected bone defects treatment. However, the ideal bone substitute biomaterials to repair infected bone defects remain scarce. In this study, we fabricated a novel magnetic nanocomposite with polycaprolactone (PCL)/Fe3O4@zinc-based imidazole zeolite framework-8 (ZIF-8) through three-dimensional (3D) printing technology. The biomaterial characterization, biocompatibility, antibacterial activity, and osteogenic ability of the 3D-printed PCL/Fe3O4@ZIF-8 nanocomposite were systematically investigated in vivo and in vitro. The 3D-printed PCL/Fe3O4@ZIF-8 nanocomposite scaffolds showed a square porous grid structure with rough surface, thermal stability, superparamagnetic character, and slow release of Zn2+. The elevation of Fe3O4@ZIF-8 concentration increased surface roughness and porosity, improved the mechanical properties, and enhanced the saturation magnetization of PCL/Fe3O4@ZIF-8 scaffolds. The PCL/Fe3O4@ZIF-8 scaffolds possessed good biocompatibility and promoted the proliferation and adhesion of rat bone marrow mesenchymal stem cells (BMSCs). The PCL/Fe3O4@ZIF-8 scaffolds also upregulated the expression of osteogenic-related genes and proteins and promoted the osteogenic differentiation of BMSCs by activating the Wnt/β-catenin signaling pathway. Furthermore, the scaffolds showed excellent antibacterial activities, which increased with increasing Fe3O4@ 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/Fe3O4@ZIF-8 nanocomposite scaffolds could serve as novel materials for the treatment of infected bone defects.