Improved osteogenesis of boron incorporated calcium silicate coatings via immunomodulatory effects.

Abstract

Osteoimmunology has revealed the importance of a favorable immune response for successful biomaterial-mediated osteogenesis. Boron-incorporated calcium silicate (Ca₁₁ Si₄ B₂ O₂₂ , B-CS) coating has been reported as a potential candidate for improving osteogenesis in orthopedic applications in vitro. However, relatively little is known about its effects on the immune response and subsequent osteogenesis. In this work, the immunomodulatory properties of the B-CS coating and its specific mechanism of action were explored. We found that the B-CS coating decreased M1 polarization and converted macrophages to the M2 phenotype via restraining the toll-like receptor signaling pathway, thus inducing a significant reduction in pro-inflammatory cytokines and an increase in anti-inflammatory cytokines. Moreover, the B-CS coating inhibited osteoclastogenesis and osteoclastic activities by downregulating osteoclastogenic genes and inhibiting the RANKL/RANK system. BMP2 and VEGF were also significantly upregulated by macrophages and bone mesenchymal stem cells, leading to activation of the BMP2 signaling pathway and subsequent upregulation of osteogenesis-associated genes, finally promoting osteogenic differentiation. These findings show that the B-CS coating could be a promising coating material for hip and knee implants. Furthermore, incorporation of the element boron into bioceramic coatings could be a good strategy in the design of bone biomaterials with beneficial immune responses. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 12-24, 2019.