Poly(amidoamine) Dendrimers as Potential Therapeutic Agents for Conservative Treatment of Irreversible Pulpitis
Lintong Yu1, Feng Yang1, Chenxi Li2
1Department of Pediatric Dentistry, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; College of Stomatology, Shanghai Jiao Tong University, Shanghai, China; National Center for Stomatology, Shanghai, China; National Clinical Research Center for Oral Diseases, Shanghai, China; Shanghai Key Laboratory of Stomatology, Shanghai, China; Shanghai Research Institute of Stomatology, Shanghai, China.
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.
