Background: The long-term success of dental implants depends on osseointegration, traditionally viewed as a biomechanical process. Recent osteoimmunology research reveals it as an immune-mediated phenomenon, where successful integration results from a redirected foreign body reaction termed Foreign Body Equilibrium (FBE). Objective: This review aims to redefine osseointegration through the lens of osteoimmunology, emphasizing macrophage polarization (M1-to-M2 switch) as the pivotal determinant of implant fate, and to evaluate strategies for immunomodulatory implant design. Methods: A comprehensive literature search was conducted using databases including PubMed, Web of Science, and Scopus. We selected and synthesized pivotal studies focusing on the cellular and molecular mechanisms of osseointegration, specifically targeting macrophage-T cell crosstalk and the RANKL-OPG axis. The review critically analyzes modulatory factors (surface topography, wettability, patient-specific conditions) and evaluates emerging therapeutic strategies such as bioactive coatings and extracellular vesicle functionalization. Conclusion: Osseointegration is an active osteoimmune process. Harnessing immunomodulation—particularly macrophage polarization—can transform implants from passive devices to therapeutic platforms, improving outcomes in diverse clinical scenarios. Keywords: osseointegration, foreign-body reaction, immunomodulation, dental implants, macrophage activation, bone-immune system
Jian et al. (Sun,) studied this question.