Coupling BCP Ceramics with Micro‐Vibration Stimulation Field for Cascade Amplification from Immune Activation to Bone Regeneration

Abstract

AbstractThe osteoimmunology has revealed that immune system plays an important role in maintaining bone metabolism and remodeling. As long‐term physiological factor in bone, mechanical stimulation such as micro‐vibration stimulation (MVS) exerts effects on regulating osteogenesis and immune response. In this study, the osteo‐immunodulatory effects of bicalcium phosphate (BCP) ceramics coupled with MVS are investigated. This results find that the combination of BCP ceramics and MVS may exert synergistic effects on the polarization and functional status of macrophages through activating plasma membrance Ca2+ ATPase (PMCA) channel, reducing the intracellular calcium ion concentration, and inhibiting downstream extracellular signal‐regulated kinase (ERK)1/2 signaling pathway. BCP ceramics coupled MVS could drive the macrophage polarization to wound‐healing M2 phenotype to decrease the production of pro‐inflammatory factors, enhance the secretion of anti‐inflammatory cytokines and growth factors such as transforming growth factor (TGF)‐β1 and bone morphogenetic protein (BMP)‐2. Moreover, BCP and MVS‐modulated macrophage secretion pattern can trigger the BMP/TGF‐Smad signaling pathways to induce osteoblastic differentiation of bone marrow mesenchymal stromal cells (BM‐MSCs) in vitro, and maintain cellular viability and promote the formation of collagen‐rich osteoid like tissues and mature blood vessels in vivo. This study demonstrates that the introduction of mechanical stimuli like non‐invasive MVS is an effective strategy to improve bone repair effects of biomaterials through endowing them with superior osteo‐immunodulatory capacity.