Remote Activation of M2 Macrophage Polarization via Magneto-Mechanical Stimulation To Promote Osteointegration

Osteoimmunomodulation has been considered to play a key role in osteointegration of orthopedic biomaterials. However, regulation of the macrophage phenotype in vivo with a spatiotemporal controllable way still remains a challenge. In this study, we designed a novel magnetic-responsive mineralized collagen coating to exert remotely controlled magneto-mechanical stimulation on macrophages using an external magnetic field. The magneto-mechanical stimulation exhibited immunomodulatory capability to activate M2 macrophage polarization via triggering the integrin-related cascade pathway and suppressing the phosphorylation of JNK in the MAPK pathway. The optimized inflammatory microenvironment subsequently promoted the osteogenic differentiation of bone marrow-derived mesenchymal stem cells and the osteointegration in vivo. This work, therefore, provides a remote spatiotemporal controllable strategy to promote the osteointegration of orthopedic biomaterials via regulation of the osteoimmune microenvironment.