Bioactive Implant Surface with Electrochemically Bound Doxycycline Promotes Bone Formation Markers In Vitro and In Vivo

Objectives: The objective of this study was to demonstrate a successful binding of Doxy hyclate onto a titanium zirconium alloy surface. Method: The coating was done on titanium zirconium coins in a cathodic polarization setup. The surface binding was analysed by SEM, SIMS, UV-Vis, FTIR and XPS. The in vitro biological response was tested with MC3T3-E1 murine pre-osteoblast cells after 14 days of cultivation and analysed in RT-PCR. A rabbit tibial model was also used to confirm its bioactivity in vivo after 4 and 8 weeks healing by means of microCT. Results: A mean of 141 µg/cm² of Doxy was found firmly attached and undamaged on the surface. Inclusion of Doxy was documented up to a depth of approximately 0.44 µm by tracing the 12C carbon isotope. The bioactivity of the coating was documented by an in vitro study with murine osteoblasts, which showed significantly increased alkaline phosphatase and osteocalcin gene expression levels after 14 days of cell culture along with low cytotoxicity. Doxy coated surfaces showed increased bone formation markers at 8 weeks of healing in a rabbit tibial model. Significance: The present work demonstrates a method of binding the broad spectrum antibiotic doxycycline (Doxy) to an implant surface to improve bone formation and reduce the risk of infection around the implant. We have demonstrated that TiZr implants with electrochemically bound Doxy promote bone formation markers in vitro and in vivo.