Abstract: Bone defects are common clinical problems in the world, and there are many biomaterials used for treating them. However, there is still a paucity of bioactive materials capable of modulating the immune microenvironment. Therefore, it is necessary to identify new therapeutic strategies to regulate the immune microenvironment of the bone defect to further promote osteogenesis. Hydroxyapatite (HAP) is an important mineral for the framework of the human body. Recently, HAP has become a key research object for bone tissue engineering applications due to its unique tailored properties and similarity to bone tissue. Here, we prepared rod-shaped HAP (rHAP) with different concentrations (0, 100, 200, and 300 µg/mL). The slowly released Ca²⁺ of 200 µg/mL rHAP can induce macrophage phenotype 2 (M2) polarization to decrease inflammatory cytokine secretion via the PI3K-Akt and Wnt/β-catenin pathways. In addition, rHAP can induce osteogenesis through the osteogenic differentiation of rat bone marrow mesenchymal stem cells. In conclusion, the 200 µg/mL rHAP shows the potential for osteoimmunomodulation in a bone defect in vitro and in vivo, which is beneficial to the treatment of bone defects.

Key words: Hydroxyapatite nanorods, Macrophage polarization, Osteoimmunomodulation, Calcium ions-related signaling pathway