Nanotopography-based strategy for the precise manipulation of osteoimmunomodulation in bone regeneration.

Immune cells play vital roles in regulating bone dynamics. Successful bone regeneration requires a favourable osteo-immune environment. The high plasticity and diversity of immune cells make it possible to manipulate the osteo-immune response of immune cells, thus modulating the osteoimmune environment and regulating bone regeneration. With the advancement in nanotechnology, nanotopographies with different controlled surface properties can be fabricated. On tuning the surface properties, the osteo-immune response can be precisely modulated. This highly tunable characteristic and immunomodulatory effects make nanotopography a promising strategy to precisely manipulate osteoimmunomdulation for bone tissue engineering applications. This review first summarises the effects of the immune response during bone healing to show the importance of regulating the immune response for the bone response. The plasticity of immune cells is then reviewed to provide rationales for manipulation of the osteoimmune response. Subsequently, we highlight the current types of nanotopographies applied in bone biomaterials and their fabrication techniques, and explain how these nanotopographies modulate the immune response and the possible underlying mechanisms. The effects of immune cells on nanotopography-mediated osteogenesis are emphasized, and we propose the concept of "nano-osteoimmunomodulation" to provide a valuable strategy for the development of nanotopographies with osteoimmunomodulatory properties that can precisely regulate bone dynamics.