Role and Mechanism of a Micro-/Nano-Structured Porous Zirconia Surface in Regulating the Biological Behavior of Bone Marrow Mesenchymal Stem Cells

Zirconia as a promising dental implant material has attracted much attention in recent years. Improving the bone binding ability of zirconia is critical for clinical applications. Here, we established a distinct micro-/nano-structured porous zirconia through dry-pressing with addition of pore-forming agents followed by hydrofluoric acid etching (POROHF). Porous zirconia without hydrofluoric acid treatment (PORO), sandblasting plus acid-etching zirconia, and sintering zirconia surface were applied as controls. After human bone marrow mesenchymal stem cells (hBMSCs) were seeded on these four groups of zirconia specimens, we observed the highest cell affinity and extension on POROHF. In addition, the POROHF surface displayed an improved osteogenic phenotype in contrast to the other groups. Moreover, the POROHF surface facilitated angiogenesis of hBMSCs, as confirmed by optimal stimulation of vascular endothelial growth factor B and angiopoietin 1 (ANGPT1) expression. Most importantly, the POROHF group demonstrated the most obvious bone matrix development in vivo. To investigate further the underlying mechanism, RNA sequencing was employed and critical target genes modulated by POROHF were identified. Taken together, this study established an innovative micro-/nano-structured porous zirconia surface that significantly promoted osteogenesis and investigated the potential underlying mechanism. Our present work will improve the osseointegration of zirconia implants and help further clinical applications.