Improved osseointegration of strontium-modified titanium implants by regulating angiogenesis and macrophage polarization

Strontium (Sr) has shown strong osteogenic potential and thereby been widely incorporated into dental and orthopedic implants. However, the improved osseointegration of strontium-modified titanium implants through regulation of angiogenesis and macrophage polarization is still beginning to be explored. Here, we demonstrated that the angiogenic capacity of human umbilical vein endothelial cells on the Sr-incorporated micro/nano titanium (SLA-Sr) surface was also significantly improved through the up-regulated expression of the HIF-1 alpha protein and Erk1/2 phosphorylation. Meanwhile, SLA-Sr not only switched macrophage polarization towards the M2 phenotype, but also expressed a high level of pro-angiogenic platelet-derived growth factor. Furthermore, macrophage secretion induced by SLA-Sr was also capable of enhancing angiogenesis of human umbilical vein endothelial cells. In vivo experimental results also showed early vascularized implant osseointegration of SLA-Sr with the type H vessel formation around the SLA-Sr implant. This study emphasized the synergistic role of Sr in the regulation of macrophage polarization and angiogenesis, and therefore depicted the therapeutic potential of SLA-Sr for rapidly vascularized osseointegration.