Osteoimmunomodulation for the development of advanced bone biomaterials

As direct effector cells for osteogenesis, osteoblastic cells are commonly used for evaluating the in vitro osteogenic capacity of bone biomaterials, and the traditional biological principle for developing bone biomaterials is to directly stimulate osteogenic differentiation. With this principle, most efforts are currently spent on optimizing the bio-mechanical and physicochemical properties to induce osteogenic differentiation of mesenchymal stem cells. This strategy has achieved certain success in the development of bone biomaterials; however, inconsistencies between in vitro and in vivo studies are not uncommon, implying the mechanisms that govern the material's capacity to mediate osteogenesis is not well-understood. Osteoimmunology has revealed the vital role of immune cells in regulating bone dynamics. Neglecting the importance of the immune response is a major shortcoming of the traditional strategy, and may explain inconsistencies between in vitro and in vivo conditions. Here, we proposed osteoimmunomodulation (OIM) in recognition of the importance of the immune response during biomaterial-mediated osteogenesis. Accordingly, we proposed the paradigm shift of bone biomaterials to an osteoimmunomodulatory material and discussed the evaluation strategy for the osteoimmunomodulation property of bone biomaterials. It is the ambition of authors that this review will change traditional methods for bone biomaterials assessment and assist in developing new bone biomaterials with the osteoimmunomodulatory property for orthopedic and dental applications.