Boron-incorporated micro/nano-topographical calcium silicate coating dictates osteo/angio-genesis and inflammatory response toward enhanced osseointegration

Abstract

Orthopedic implant coatings with optimal surface features to achieve favorable osteo/angio-genesis and inflammatory response would be of great importance. However, to date, few coatings are capable of fully satisfying these requirements. In this work, to take advantage of the structural complexity of micro/nano-topography and benefits of biological trace elements, two types of boron-containing nanostructures (nanoflakes and nanolamellars) were introduced onto plasma-sprayed calcium silicate (F-BCS and L-BCS) coatings via hydrothermal treatment. The C-CS coating using deionized water as hydrothermal medium served as control. Boron-incorporated CS coating stimulated osteoblastic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Specifically, the combination of β1 integrin-vinculin-mediated cell spreading and activation of bone morphogenetic protein signaling pathway acted synergistically to cause significant upregulation of runt-related transcription factor 2 (RUNX2) protein and Runx2 gene expression in BMSCs on the F-BCS coating surface, which induced the transcription of downstream osteogenic differentiation marker genes. F-BCS coating allowed specific boron ion release, which favored angiogenesis as evidenced by the enhanced migration and tube formation of human umbilical vein endothelial cells in the coating extract. Boron-incorporated coatings significantly suppressed the expression of toll-like receptor adaptor genes in RAW264.7 macrophages and subsequently the degradation of nuclear factor-κB inhibitor α, accompanied by the inactivation of the downstream pro-inflammatory genes. In vivo experiments confirmed that F-BCS-coated Ti implant possessed enhanced osseointegration compared with L-BCS- and C-CS-coated implants. These data highlighted the synergistic effect of specific nanotopography and boron release from orthopedic implant coating on improvement of osseointegration.