Dynamic protein corona influences immune-modulating osteogenesis in magnetic nanoparticle (MNP)-infiltrated bone regeneration scaffolds in vivo

An inflammatory reaction initiates fracture healing and directly influences the osteoinductive effect of the magnetic hydroxyapatite (MHA) scaffold, but the underlying mechanism is yet to be elucidated. Protein corona as a real biological identity of a biomaterial significantly affects the biological function of the bone regenerative scaffold. Hence, we developed a simple and effective in vivo dynamic model for the protein corona of MHA scaffolds to predict the correlation between the inflammatory reaction and bone wound healing, as well as the underlying mechanism governing such a process. Certain proteins including proteins related to the immune response and inflammation, bone and wound healing, extracellular matrix, cell behavior, and signaling increased in the protein corona of the magnetic nanoparticle (MNP)-infiltrated scaffolds in a time-dependent manner. Moreover, the enriched proteins related to the immune response and inflammation adsorbed on the MHA scaffolds correlated well with the proteins that significantly enhanced bone wound healing, as suggested by the same variation tendency of the proteins related to bone and wound healing, and immune response and inflammation. The presence of MNPs suppressed the chronic inflammatory responses and highly promoted the acute inflammatory responses. More importantly, the activation of the acute inflammatory responses led to the recruitment of immune cells, remodeling of the extracellular matrix and even the acceleration of bone healing. The bone repair in vivo model and inflammatory cytokine in vitro model results further corroborated the critical involvement of inflammatory reaction in enhancing bone wound healing. This opens up the great potential of protein corona formation to understand the complicated mechanisms involved in immune-modulated bone wound healing.