Strategies for advanced particulate bone substitutes regulating the osteo-immune microenvironment.

The usage of bone substitute granule materials has improved the clinical results of alveolar bone deficiencies treatment and thus broadened applications in implant dentistry. However, because of the complicated mechanisms controlling the foreign body response, no perfect solution can avoid the fibrotic encapsulation of materials till now, which may impair the results of bone regeneration, even cause the implant materials rejection. Recently, the concept of 'osteoimmunology' has been stressed. The outcomes of bone regeneration are proved to be related to the bio-physicochemical properties of biomaterials, which allow them to regulate the biological behaviours of both innate and adaptive immune cells. With the development of single cell transcriptome, the truly heterogeneity of osteo-immune cells has been clarifying, which is helpful to overcome the limitations of traditional M1/M2 macrophage nomenclature and drive the advancements of particulate biomaterials applications. This review aims at introducing the mechanisms of optimal osseointegration regulated by immune systems and provides feasible strategies for the design of next generation 'osteoimmune-smart' particulate bone substitute materials in dental clinic.