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

Abstract

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.

The evidence of a macrophage barrier in the xenotransplantation of human hematopoietic stem cells to severely immunodeficient rats

“…In the case of one‐time CL injection, macrophages appear again about 4 days after the administration; this is consistent with findings from previous studies 35‐37 . Furthermore, repeated CL injection was considered in several reports 32,37 .…”

In Vivo Biological Evaluation of Biodegradable Nanofibrous Membranes Incorporated with Antibiofilm Compounds

“…Similarly, inflammatory cells and giant cells associated with barrier membranes were recognized as a compromised healing sign [ 62 ]. While the exact mechanism of macrophage polarization and interaction with biomaterials remains unclear, recent studies have suggested that macrophages might have no deleterious effect on final formation of osseointegration [ 63 , 64 , 65 ] and that inflammatory infiltration were not able to inhibit bone regeneration [ 5 , 60 , 66 ]. Since this present study was limited to the biologic response of the implanted membranes incorporated with antibiofilm, further work that addresses functionality in promoting bone regeneration will be conducted before extrapolating to more statements in that direction.…”

Osteoimmunology drives dental implant osseointegration: A new paradigm for implant dentistry

“…It has been postulated that monocytic-derived cells, possibly osteomacs, arrive at the titanium implant surface differentiating into pro-regenerative M2 and then recruiting osteoprogenitor cells to build the peri-implant new bone [ 57 ]. In fact, a macrophage depleted model showed both a reduced number of osteoblasts and less bone formation around implants [ 58 ].…”