Modulation of Macrophage Polarization for Bone Tissue Engineering Applications

Innate immune cells play a crucial role in bone development and repair. Macrophages are the main effector cells in immune responses to implants and are indispensable for bone healing success. The heterogeneity and plasticity of macrophages make them a prime target for immune system modulation to enhance bone repair and regeneration. It is believed that the polarization of macrophage phenotype towards the anti-inflammatory M2, rather than the inflammatory M1 phenotype, promotes osteogenesis. Tissue-engineered bioimplants are potentially capable of producing signals to modulate macrophage polarization. Therefore, development of smart immunomodulatory bioimplants via manipulation of their properties seem a promising strategy for tuning immune responses to optimize bone repair without any unwanted inflammatory reactions. The purpose of the present review is to summarize the currently available studies performed on the effects of macrophage polarization, especially towards M2 phenotype, both in bone repair and in bioimplant-stimulated osteogenesis. Moreover, this literature highlights the need to focus future studies on the development of smart immunomodulatory implants capable of switching macrophage polarization-enhancing bone implant-host tissue integration.