One-step co-doping of ZnO and Zn2+ in osteoinductive calcium phosphate ceramics with synergistic antibacterial activity for regenerative repair of infected bone defect

Abstract

How to endow bone grafts with long-term antibacterial activity and good bone regenerative ability to achieve the regenerative repair of infected bone defects has been the focus of the clinical treatment of osteomyelitis. The present study introduced a novel one-step route to realizing the co-doping of zinc oxide (ZnO) and zinc ion (Zn2+) in biphasic calcium phosphate (BCP) ceramics to utilize their synergistic antibacterial. Compared with the conventional BCP ceramics (BCP-Ca), the ZnO/Zn2+ co-doping ones (BCP-Zn) possessed strong antibacterial ability on E. coli and S. aureus as well as stimulated the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) effectively. The synergistic antibacterial mechanism of ZnO and Zn2+ was also investigated. BCP-Zn showed excellent osteoinductivity and angiogenesis at three months postoperatively in the canine intramuscular implantation model. Moreover, BCP-Zn exhibited excellent anti-infective ability and bone regenerative repair compared to BCP-Ca and control groups in the infected bone defect model of rat femur. Collectively, these findings suggest that the simultaneous introduction of ZnO/Zn2+ could have immense potential to expand the application of osteoinductive BCP ceramics in the regenerative repair of infected bone defects.