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Periodontal disease is a highly prevalent chronic inflammatory condition worldwide, significantly impairing patients’ quality of life and imposing a substantial burden on healthcare systems. In recent years, significant progress has been made in the immunopathogenesis of periodontal diseases, highlighting the crucial role of immune regulation in restoring periodontal homeostasis and promoting tissue regeneration. Meanwhile, the rapid development of osteoimmunology in tissue engineering has provided a theoretical framework for elucidating periodontal bone regeneration from the perspective of immune–bone coupling and offered new insights into therapeutic optimization. This review systematically summarizes the osteoimmunological basis of periodontal bone regeneration, focusing on how the physicochemical properties of biomaterials modulate the periodontal osteoimmune microenvironment. Recent progress in osteoimmunomodulatory biomaterials for periodontal bone regeneration is summarized, highlighting strategies involving physical and chemical modifications, bioactive molecule enhancements, as well as cell- and cell-derived product–based modifications. Considering the complexity of the periodontal immune microenvironment, advances in stimuli-responsive biomaterials for immune modulation and their roles in periodontal bone regeneration are further discussed. Finally, key challenges in material design and clinical translation of osteoimmunomodulatory biomaterials are addressed, and future perspectives are proposed to provide theoretical guidance for the rational design and translational development of immunomodulatory biomaterials for periodontal bone regeneration.

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