Osteoimmunomodulatory Effects of Enamel Matrix Derivate and Strontium Coating Layers: A Short- and Long-Term In Vivo Study

[Image: see text] Over the past few years, surface modification of implant surfaces has gained substantial attention as a promising solution to avoid the failure of biomaterials after implantation. Although researchers suggest several strategies for surface functionalization of titanium-based implants, only a few studies have compared the osteoimmunomodulatory effects of ionic nanostructures and biofunctionalization in the same biological model. Enamel matrix derivate (EMD) and strontium are both known for their positive influences on bone cell responses. In this study, we functionalized the titanium–zirconium implant surface with EMD and strontium using an electrochemical cathodic polarization method. Afterward, we evaluated the osteoimmunomodulatory effects of EMD or strontium coated titanium–zirconium implants in the tibia of eight Gray Bastard Chinchilla rabbits. We performed 2 and 3D micro-CT, wound fluid, histologic, and histomorphometric analyses on bone tissues after 4- and 8-weeks of implantation. Although the results could indicate some differences between groups regarding the bone quality, there was no difference in bone amount or volume. EMD stimulated higher ALP activity and lower cytotoxicity in wound fluid, as well as a lower expression of inflammatory markers after 8 weeks indicating its osteoimmunomodulatory effects after implantation. Overall, the results suggested that ionic nanostructure modification and biofunctionalization might be useful in regulating the immune responses to implants.