Macrophages in dental pulp: dynamic regulators of microenvironmental homeostasis and therapeutic targets in pulpitis

Abstract

Abstract The dental pulp is a soft connective tissue enclosed by mineralized dentin, containing odontoblasts, dental pulp stem cells (DPSCs), fibroblasts, endothelial cells, nerves, and immune cells. Under physiological and pathological conditions, these cells collectively regulate the dentin-pulp microenvironment. Macrophages are key immune cells in this niche, participating not only in host defense and inflammatory amplification but also in apoptotic cell clearance, angiogenesis, extracellular matrix remodeling, and reparative dentinogenesis. Recent studies indicate that dental pulp macrophages should not be interpreted solely through the classical M1/M2 dichotomy; instead, their activation states are shaped by local microbial, neural, vascular, and stromal signals. In this review, we summarize current evidence on the origin, phenotype, and function of macrophages in the dental pulp, with particular emphasis on their interaction with DPSCs under inflammatory conditions. We further discuss macrophage-related therapeutic strategies for pulpitis and regenerative endodontics, including modulation of macrophage recruitment, inflammatory resolution, paracrine signaling, extracellular vesicles, and biomaterial-based immunomodulation. Finally, we highlight current limitations and future directions, particularly the need to integrate clinical pulp samples, single-cell/spatial omics, and functional validation to define macrophage states within the dentin-pulp-immune axis.