Biofunctional magnesium-coated Ti6Al4V scaffolds promote autophagy-dependent apoptosis in osteosarcoma by activating the AMPK/mTOR/ULK1 signaling pathway

The recurrence of osteosarcoma (OS) after reconstruction using Ti6Al4V prostheses remains a major problem in the surgical treatment of OS. Modification of the surfaces of Ti6Al4V prostheses with antitumor functions is an important strategy for improving therapeutic outcomes. Magnesium (Mg) coating has been shown to be multifunctional: it exhibits osteogenic and angiogenic properties and the potential to inhibit OS. In this study, we determined the proper concentration of released Mg2+ with respect to OS inhibition and biosafety and evaluated the anti-OS effects of Mg-coated Ti6Al4V scaffolds. We found that the release of Mg2+ during short-term and long-term degradation could significantly inhibit the proliferation and migration of HOS and 143B cells. Increased cell apoptosis and excessive autophagy were also observed, and further evidence of AMPK/mTOR/ULK1 signaling pathway activation was obtained both in vitro and in vivo, which suggested that the biofunctional scaffolds induce OS inhibition. Our study demonstrates the ability of an Mg coating to inhibit OS and may contribute to the further application of Mg-coated Ti6Al4V prostheses.
Graphical abstract Schematic diagram showing the induction of autophagy and apoptosis in OS cells by Mg-coated biofunctional Ti6Al4V scaffolds.Image 1
Highlights • Multifunctional Mg coating is considerable surface modification for Ti6Al4V prostheses. • Mg2+ releasing by the scaffolds could significantly inhibit the proliferation and migration of OS cells. • The biofunctional scaffolds could inhibit OS by activating autophagy-dependent apoptosis. • The AMPK/mTOR/ULK-1 pathway was involved in autophagy-depended apoptosis induced by the scaffolds.