Surface modification of titanium implants by ZIF-8@Levo/LBL coating for inhibition of bacterial-associated infection and enhancement of in vivo osseointegration

Abstract

Bone implant-associated infection is one of the major concerns in orthopedics, and may even result in implant failure. To this end, we developed a strategy for the fabrication of an antibacterial coating on titanium (Ti) implants with pH-response to combat bacteria-mediated acidification of the local microenvironment. It includes three steps: first, we synthesized levofloxacin (Levo)-loaded zeolitic imidazolate framework-8 (ZIF-8@Levo) nanoparticles; second, the nanoparticles were loaded onto the collagen-modified Ti substrates by the cathode electrophoresis deposition (EPD) method; third, gelatin (Gel) and chitosan (Chi) multilayers were spin-coated on the modified Ti substrates, since the chelating effect of Gel and Chi would reduce the hydrolysis of ZIF-8@Levo for a sustained release of Levo and Zn2+. The fabricated samples of MOF@Levo/LBL promoted in vitro adhesion, proliferation, and differentiation of osteoblasts. Moreover, the MOF@Levo/LBL samples exhibited strong antibacterial ability against Escherichia coli and Staphylococcus aureus through hydrolysis of ZIF-8 nanoparticles, thereby creating a marginally alkaline microenvironment. Furthermore, in vivo implantation in a femur-infected rat model revealed that MOF@Levo/LBL implants effectively inhibited bacterial adhesion, apart from significantly improving osseointegration of the Ti implants. The study provides a promising alternative for fabricating multifunctional Ti implants with strong antibacterial capacity and enhanced bone formation for potential orthopedic application.