Inflammation and biomaterials: role of the immune response in bone regeneration by inorganic scaffolds.

The regulatory role of the immune system in maintaining bone homeostasis and restoring its functionality, when disturbed due to trauma or injury, has become evident in recent years. The polarization of macrophages, one of the main constituents of the immune system, into the pro-inflammatory or anti-inflammatory phenotype has great repercussions for cellular crosstalk and the subsequent processes needed for proper bone regeneration such as angiogenesis and osteogenesis. In certain scenarios, the damaged osseous tissue requires the placement of synthetic bone grafts to facilitate the healing process. Inorganic biomaterials such as bioceramics or bioactive glasses are the most widely used due to their resemblance to the mineral phase of bone and superior osteogenic properties. The immune response of the host to the inorganic biomaterial, which is of an exogenous nature, might determine its fate, leading either to active bone regeneration or its failure. Therefore, various strategies have been employed, like the modification of structural/chemical features or the incorporation of bioactive molecules, to tune the interplay with the immune cells. Understanding how these particular modifications impact the polarization of macrophages and further osteogenic and osteoclastogenic events is of great interest in view of designing a new generation of osteoimmunomodulatory materials that support the regeneration of osseous tissue during all stages of bone healing.