The role of macrophages in osseointegration of dental implants: An experimental study in vivo.

To investigate the role of macrophages in the osseointegration of dental implants through induced macrophage reduction in a murine model. Fifty-four Sprague-Dawley rats with bilateral maxillary first molars replaced by titanium implants were randomly assigned into three groups. For the test group, macrophages were depleted by tail-vein injection of clodronate liposome (20 mg/kg) 3 days before implantation and reinjection every 3 days until the sacrifice of the rats (10 mg/kg). Animals treated with Phosphate Buffer saline (PBS) alone or empty liposome were included as controls. Samples contained implants were retrieved after 3, 7, 14, and 28 days, and the alterations of macrophages (CD68) and osteoblasts (Osterix) were evaluated using histology and immunohistochemistry technique. Histological analysis showed that new bone gradually formed within the lateral chamber regions in both the Control group and the Lip group, whereas bone healing was delayed at the first 2-weeks despite of pronounced newly formed peri-implant bone at 4 weeks in the Lipclod group. The bone-to-implant contact was significantly higher in the Lip and Control group than in the Lipclod group after 2 weeks. Immunohistochemical analysis showed that CD68+ cells were present both in the central region and in direct contact with implant surface throughout the healing period. Macrophages depletion reduced osteoblast amounts and new bone formation around implants in the first 2 weeks, and have no adverse impacts on the final formation of osseointegration. Macrophages play a dual role in both regulating the bone healing process and immune response to implant installation during the early stages.