Modulating autophagy by strontium-doped micro/nano rough titanium surface for promotion of osteogenesis and inhibition of osteoclastogenesis

Abstract

Although it has been demonstrated that implant surfaces treated with strontium (Sr) promote osseointegration, the underlying intracellular mechanism remains unknown. Autophagy is a vital intracellular degradation mechanism that plays an essential role in maintaining bone homeostasis. Therefore, while designing implant biomaterials, it is critical to consider the autophagy mechanism. In this study, we fabricated Sr-doped micro/nano rough titanium implant surface by hydrothermal treatment (SLA+Sr). The in vitro results revealed that the SLA+Sr surface promoted osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) via autophagy activation. The SLA+Sr surface, on the other hand, inhibited osteoclast differentiation by downregulating autophagy. Additionally, in vivo, the SLA+Sr implant improved osseointegration, inhibited osteoclastogenesis, and upregulated autophagy levels in surrounding bone tissue cells. Our findings established a novel centralized mechanism by which SLA+Sr regulated osteogenesis and osteoclastogenesis during the osseointegration process through autophagy regulation. Moreover, endowing implants with the ability to modulate autophagy may be a promising strategy for enhancing implant osseointegration in the future translational medicine field.

Keywords: Autophagy; Implant; Osseointegration; Osteoclastogenesis; Strontium.