Effects of biodentine and MTA on calcification, pyroptosis, and necroptosis in an inflammatory DPSC–macrophage coculture model

To explore the effects of Biodentine and Mineral Trioxide Aggregate (MTA) on calcification, inflammation, and cell death pathways in an inflammatory coculture model of dental pulp stem cells (DPSCs) and macrophages under lipopolysaccharide (LPS) treatment. Specifically, how these materials influence calcium deposition and cell death responses, including apoptosis, autophagy, necroptosis, and pyroptosis was analysed. DPSCs were cocultured with THP-1 macrophage cells and then exposed to Biodentine or MTA. Proliferation, migration, calcium deposition, and mRNA expression levels of inflammatory and cell death markers were determined. In the LPS-THP-1 inflammatory coculture model, Biodentine promoted calcium deposition significantly, while MTA had minimal effect. Biodentine suppressed alkaline phosphatase ( ALPL ) but enhanced dentin sialophosphoprotein ( DSPP ) expression, while MTA enhanced ALPL and DSPP expression. Biodentine and MTA also reduced the expression of key inflammatory markers (interleukin 6 [ IL6 ] and interleukin 8 [ IL8 ]). Both materials modulated cell death pathways differently. Biodentine suppressed necroptosis and pyroptosis, while MTA reduced pyroptosis but enhanced necroptosis. Despite these differences, neither Biodentine nor MTA significantly affected apoptosis or autophagy. In the LPS-THP-1 inflammatory coculture model, Biodentine demonstrated a stronger ability to promote calcium deposition but this may not be through the DSPP and ALPL pathway. Further investigation is needed to fully understand the molecular mechanisms and how the LPS-THP-1 inflammatory coculture model with DPSCs may relate to clinical outcomes, particularly in the context of canal calcification following Biodentine-based vital pulp therapy. The cell death-related genes expression triggered by MTA and Biodentine may suggest potential differences in their biological effects, which could have implications for their future clinical applications.