Poly(amidoamine) Dendrimers as Potential Therapeutic Agents for Conservative Treatment of Irreversible Pulpitis.

Introduction: Although cell-free DNA (cfDNA) is involved in several inflammation-related diseases, its role in pulp inflammation remains unclear. The aims of this study were to explore the role of cfDNA in the development of irreversible pulpitis and to identify a potential therapeutic strategy.

Methods: Pulpitis plasma samples were collected from patients diagnosed with irreversible pulpitis, and the cfDNA concentration associated with pulpitis was measured using a Quant-iT PicoGreen dsDNA kit. Dental pulp stem cells and Tohoku Hospital Pediatrics -1 macrophages were stimulated with pulpitis plasma, and the expression of inflammatory factors was investigated via real-time reverse transcription PCR and ELISA. Toll-like receptor 9 expression in pulpitis blood-derived cells was analyzed by flow cytometry. Finally, the effects of cationic poly(amidoamine) (PAMAM) on the treatment of inflammation in vitro and in a rat pulpitis model were evaluated.

Results: We first revealed that pulpitis-derived plasma had elevated cfDNA levels, which caused M1-like macrophage polarization through the toll-like receptor 9 signaling pathway and then induced an inflammatory response in dental pulp stem cells. M1-like macrophage polarization affected the pulp inflammatory microenvironment and could be reversed via a synergistic effect of irrigation and cationic PAMAM for cfDNA scavenging. PAMAM has shown potential for inhibiting inflammatory M1-like macrophage polarization and alleviating pulpitis at the cellular and organism levels.

Conclusions: This study elucidated the importance of cfDNA in pulpitis and provides a potential therapeutic strategy. cfDNA scavenging could alleviate the inflammatory response in pulpitis and potentially preserve more vital pulp for teeth with irreversible pulpitis.