Macrophages contribute to periodontal wound healing mainly in the tissue proliferation stage

The aim of this study was to determine the preliminary role of macrophages in different stages of periodontal healing.

Macrophages are promising target cells for periodontal regeneration. However, the stage at which they play a more important role during periodontal repair has not been elucidated till date.

First, the dynamic changes in M1 and M2 macrophages were analyzed in a rat periodontal-defect model at Days 1, 3, 5, 7, 14, 21, and 28 post-surgery. Macrophages were then depleted after 1, 6, and 14 days of surgery, and the healing results were evaluated via micro-computed tomography and histopathological detection. Finally, the effects of M1 and M2 macrophages on the proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs) were verified in vitro.

During natural periodontal healing, the number of M1 macrophages increased the most during the early stage of healing (3 days post-operation), and subsequently, it decreased rapidly. The number of M2 macrophages was at its peak during the middle and late stages of tissue healing (5-21 days post-surgery). Interestingly, the highest number of M2 macrophages was observed at 5-14 days post-operation in the alveolar bone, while it was observed at 21 days post-operation in the cementum area. On the first and 14th day post-operation, the clearance of macrophages had no significant effect on tissue healing; however, on the sixth day post-operation, macrophage depletion significantly inhibited tissue regeneration (p < .05). In vitro studies showed that M2 macrophages, rather than M1 macrophages, could significantly promote the proliferation of MSCs (p < .01).

It is better to intervene in tissue proliferation phase when a M2 macrophage regulation-based periodontal regenerative therapy is planned in the future.