The effect of compressive force in bone tissue induced by implants of different primary stabilities on macrophage polarization and bone regeneration

Dental implants with different primary stabilities give rise to distinct stress distributions at the implant-bone interface after placement and exert mechanical force on the cells in the bone tissue. This study aimed to investigate whether the mechanical forces in peri-implant bone participate in the body's immune response and influence macrophage polarization. Therefore, an in vivo rat implantation model with different primary implant stabilities was established. The osteoimmune response and macrophage polarization were investigated, and the osseointegration of the implants was evaluated. In an in vitro experiment, an external compressive force was applied to RAW264.7 cells, and the polarization phenotype was observed. MC3T3-E1 cells were cultured in macrophage-conditioned medium to investigate the regulatory effect of the macrophage-secreted cytokines on the osteogenic differentiation of osteoblasts. In vivo experimental results indicated that the primary stability of implants is positively correlated with the mechanical force. The osteoimmune response was significantly amplified by compressive force generated from implants. This compressive force first induced both M1 and M2 macrophage polarization and then accelerated the progression of the transition to M2 macrophages in the bone repair phase. In vitro, compressive force significantly upregulated the M1 and M2 macrophage polarization. In addition, the suppressive effect of macrophages on the osteogenesis of MC3T3 cells was relieved by cytokines secreted by macrophages under compressive force loading, which promoted their osteogenesis. Overall, these results clarify that compressive force from different primary stabilities is an important influencing factor regulating the osteoimmunne response and macrophage polarization in addition to maintaining the implant.