Preparation of antibacterial and osteoconductive 3D-printed PLGA/Cu(I)@ZIF-8 nanocomposite scaffolds for infected bone repair

Abstract

Background: The repair of large bone defects is a great challenge in clinical practice. In this study, copper-loaded-ZIF-8 nanoparticles and poly (lactide-co-glycolide) (PLGA) were combined to fabricate porous PLGA/Cu(I)@ZIF-8 scaffolds using three-dimensional printing technology for infected bone repair. Methods: The surface morphology of PLGA/Cu(I)@ZIF-8 scaffolds was investigated by transmission electron microscopy and scanning electron microscopy. The PLGA/Cu(I)@ZIF-8 scaffolds were co-cultured with bacteria to determine their antibacterial properties, and with murine mesenchymal stem cells (MSCs) to explore their biocompatibility and osteoconductive properties. The bioactivity of the PLGA/Cu(I)@ZIF-8 scaffolds was evaluated by incubating in simulated body fluid. Results: The results revealed that the PLGA/Cu(I)@ZIF-8 scaffolds had porosities of 80.04 ± 5.6% and exhibited good mechanical properties. When incubated with H 2 O 2 , Cu(I)@ZIF-8 nanoparticles resulted generated reactive oxygen species, which contributed to their antibacterial properties. The mMSCs cultured on the surface of PLGA/Cu(I)@ZIF-8 scaffolds were well-spread and adherent with a high proliferation rate, and staining with alkaline phosphatase and alizarin red was increased compared with the pure PLGA scaffolds. The mineralization assay showed an apatite-rich layer was formed on the surface of PLGA/Cu(I)@ZIF-8 scaffolds, while there was hardly any apatite on the surface of the PLGA scaffolds. Additionally, in vitro, Staphylococcus aureus cultured on the PLGA/Cu(I)@ZIF-8 scaffolds were almost all dead, while in vivo inflammatory cell infiltration and bacteria numbers were dramatically reduced in infected rats implanted with PLGA/Cu@ZIF-8 scaffolds. Conclusion: All these findings demonstrate that PLGA/Cu(I)@ZIF-8 scaffolds possess excellent antibacterial and osteoconductive properties, as well as good biocompatibility and high bioactivity. This study suggests that the PLGA/ Cu(I)@ZIF-8 scaffolds could be used as a promising biomaterial for bone tissue engineering, especially for infected bone repair.

Biological applications of copper-containing materials

“…In addition, implant-related infection is a devastating complication following the application of a medical implant. For example, implant-related infection in orthopedics has become a common problem against the background of a markedly increasing number of implant surgeries being performed [ [92] , [93] , [94] ]. In the United States, implant-related infection is the main cause of total knee arthroplasty, accounting for more than 20% of all cases, and severe infection may lead to amputation [ 95 , 96 ].…”

Sustainable drug release from polycaprolactone coated chitin-lignin gel fibrous scaffolds

“…This implies that the core layer is the leading contributor to the morphology and size distribution of the core-shell fibers. This might be associated with the high electrical conductivity of the core solution 50 . It was reported previously that the sol-gel CL solution (i.e.…”

3D Printing of Metal/Metal Oxide Incorporated Thermoplastic Nanocomposites With Antimicrobial Properties

“…With the integration of M/MO nanoparticles, bacterial infection can be avoided during surgical implantation, which otherwise could affect tissue growth, postpone surgical recovery, upsurge risks of complications, and even cause death ( Abudula et al, 2020 ). For example, Zou et al (2020) prepared nanocomposite scaffolds containing poly(lactic-co-glycolic acid) (PLGA), copper/zinc based zeolitic-imidazolate-frameworks (Cu@ZIP-8) by FDM-based 3D printing for infected bone repair application. They suggested that a sustainable release of Cu@ZIP-8 in aqueous media ensures long-term antibacterial efficacy of the developed scaffolds ( Zou et al, 2020 ).…”

“…For example, Zou et al (2020) prepared nanocomposite scaffolds containing poly(lactic-co-glycolic acid) (PLGA), copper/zinc based zeolitic-imidazolate-frameworks (Cu@ZIP-8) by FDM-based 3D printing for infected bone repair application. They suggested that a sustainable release of Cu@ZIP-8 in aqueous media ensures long-term antibacterial efficacy of the developed scaffolds ( Zou et al, 2020 ). Afghah et al (2020) developed a PCL-poly propylene succinate (PCL-PPSu) composite with silver-doped biocidal properties, which can be printable by FDM.…”