Micro-/nano-structured zirconia surface promotes osteogenic differentiation of human bone marrow mesenchymal stem cells by reducing pyroptosis under inflammatory conditions.

BACKGROUND/PURPOSE: Promoting osteogenesis under inflammatory conditions holds promise for preventing and mitigating peri-implantitis. Cell pyroptosis inhibits osteoblast-mediated bone formation. Although the surface topography of implant materials influences both osteogenesis and inflammatory responses, its effects on pyroptosis and osteogenesis under inflammatory conditions have not been thoroughly investigated. The aim of this study was to investigate the effects of a porous and hydrofluoric acid-etched micro-/nano-structured zirconia (POROHF) surface on pyroptosis and osteogenesis of human bone marrow mesenchymal stem cells (hBMSCs) under inflammatory conditions. MATERIALS AND METHODS: Lipopolysaccharide (LPS) and adenosine 5'-triphosphate (ATP) were used to induce pyroptosis in hBMSCs and evaluate the effects of pyroptosis on osteogenesis of hBMSCs. Then, using commonly used sandblasted acid-etched titanium and zirconia surfaces as controls, the effects of POROHF surface on pyroptosis and osteogenesis under inflammatory conditions simulated by LPS and ATP were evaluated. To clarify the potential mechanisms by which the surface affected pyroptosis of hBMSCs, RNA sequencing and functional verification were also performed. RESULTS: LPS and ATP induced caspase-1/GSDMD-mediated pyroptosis in hBMSCs and thereby inhibited osteogenic differentiation and angiogenic potential of hBMSCs, which could be partially reversed by inhibiting pyroptosis. The POROHF surface could reduce pyroptosis levels, thereby promoting osteogenesis of hBMSCs under inflammatory conditions. The surface reduced pyroptosis of hBMSCs by downregulating EGR1 expression and upregulating MANF expression. CONCLUSION: This study highlighted the inhibitory effects of caspase-1/GSDMD-mediated pyroptosis on osteogenesis of hBMSCs and demonstrated that micro-/nano-structured zirconia surface could promote osteogenic differentiation of hBMSCs by reducing pyroptosis under inflammatory conditions.