The combined effects of nanotopography and Sr ion for enhanced osteogenic activity of bone marrow mesenchymal stem cells (BMSCs)

Both surface topography and chemistry have a significant influence on the biological performance of orthopedic implant coatings. In our study, a surface modification strategy embodying bioactive trace element incorporation and nanotopography construction was employed to enhance the osteogenic activity of calcium silicate (Ca-Si) coatings. We developed strontium-loaded nanolayer on plasma sprayed Ca-Si (CS) coating via hydrothermal treatment which was denoted as Sr-NT-CS. The original CS coating and the CS coating modified with similar nanotopography (NT-CS) were studied in parallel. We investigated the cellular effects of surface topography and released Sr ion on the adhesion, proliferation, differentiation, and mineralization of BMSCs and the associated molecular mechanisms. The results indicated that the nanotopography activated integrin β1, promoted the spread of BMSCs into a polygonal osteoblastic shape, and induced higher levels of collagen secretion. The Sr incorporation stimulated osteogenic differentiation and mineralization as indicated by the increases in ALP activity and mineralized nodules formation. The examination of gene expressions revealed that Sr ion exerted the effects by interacting with extracellular calcium sensitive receptor (CaSR), and combined with the nanotopographical cue for the up-regulation of osteogenic master transcription factor Runx2. The promoted Runx2 subsequently affected osteoblast (OB) marker genes (BMP-2, BSP, OPN, and OCN), thus driving BMSCs to differentiate into OBs. Moreover, the Sr incorporation inhibited osteoclastogenesis, as indicated by the down-regulation of interleukin-6 (IL-6) and the inhibition of RANKL/RANK system. Those results suggested that our developed Sr-NT-CS coating have combined the effects of nanotopography and Sr ion for enhanced osteogenic activity of BMSCs.