Macrophage-induced immunomodulation in oral tissue repair and regeneration: Recent advances and future perspectives
Yujie Wang, Jing Mao, Yifan Wang, Rui Wang, Dajie Duan, Zhenyuan Liu, Xiaohan Hu, Zi‐Li Yu, Xin Shi
Abstract
• This review provides a comprehensive analysis of the ontogeny and tissue-specific distribution of macrophages. • The diverse polarization phenotypes of macrophages, namely M1, M2a, M2b, M2c, and M2d, are discussed in detail, along with their respective secretory profiles, including both soluble factors and insoluble exosomes. • Particular emphasis is placed on elucidating the regulatory mechanisms and immunotherapeutic potential of macrophages within the context of various oral pathologies, including periodontitis, pulpitis, peri-implantitis, and jawbone defects. • Future insightful perspectives for modulating macrophage polarization are highlighted, with the aim of proposing novel immunotherapeutic strategies and promising directions for the prevention and management of oral diseases. Maintaining immune balance plays crucial roles in the development and prognosis of injured oral tissues. Serving as critical components of immune system, macrophages are essential in accelerating oral tissue repair and regeneration. This multipart review intends to present a comprehensive overview of recent advances and future perspectives of macrophage plasticity and polarization in oral tissue repair and regeneration, thereby enhancing the understanding of macrophage-induced immunotherapeutic effects and underlying mechanisms in oral diseases. The primary electronic databases consulted for this review included PubMed, Web of Science, and Scopus. The literature search strategy employed a comprehensive combination of keywords such as “macrophage polarization”, “M1”, “M2”, “oral tissue repair”, “periodontitis”, “pulpitis”, “osseointegration”, “jawbone defect”, and “immunotherapy”. Both original research articles and authoritative review papers were selected. Furthermore, the reference lists of retrieved articles were manually examined to identify additional pertinent publications. Macrophages are derived initially from hematopoietic stem cells in the bone marrow and embryonic yolk sac progenitor cells. They encompass several polarization phenotypes, including M1, M2a, M2b, M2c, and M2d, and exert multifaceted functions by secreting soluble factors and insoluble exosomes. Encouragingly, robust immunotherapeutic potential and distinctive regulatory mechanisms of macrophages have been revealed for a variety of oral diseases, providing a breadth of perspectives and insights into the repair and regeneration of oral tissues. Orderly and sequential polarization of macrophages has been proposed as novel immunotherapeutic strategies and promising directions for treating oral diseases. An in-depth exploration of hidden mechanisms may contribute to structural regeneration and functional reconstruction of oral tissues.