Comprehensive process optimization for rapidly vascularized osseointegration by dual ions effects

Abstract

Osseointegration involves a series of sophisticated physiological processes including osteoimmune responses, angiogenesis, and osteogenesis. However, a comprehensive process optimization to tackle the dilemma of the prolonged implant osseointegration still remains a challenge. In this study, we designed a micro/nanoscaled hierarchical topography and simultaneously incorporated strontium ions and zinc ions onto titanium surface (SLA-Sr/Zn). SLA-Sr/Zn exhibited potent pro-angiogenic capacity in vitro by expressing essential angiogenic genes and activating Akt/HIF-1α signaling pathway of human umbilical vein endothelial cells. Meanwhile, SLA-Sr/Zn exerted robust osteogenic potential by facilitating bone mesenchymal stem cells osteogenic differentiation. Furthermore, the continuous release of dual ions orchestrated a favorable osteoimmune microenvironment by modulating macrophage polarization towards M2a phenotype and up-regulated expression of platelet-derived growth factor. In vivo study corroborated the excellent efficacy of SLA-Sr/Zn implant on promoting vascularized osseointegration by augmenting type H vessel generation. Collectively, the distinct SLA-Sr/Zn titanium implant surface exerted versatile biological functions in angiogenesis, osteogenesis and osteoimmunomodulation, rendering its therapeutic potential for rapidly vascularized osseointegration.