An innate defense regulator peptide modulates the inflamed pulp microenvironment and promotes pulp repair

Persistent infection and unresolved inflammation remain major obstacles to successful vital pulp therapy. Strategies capable of simultaneously controlling bacterial burden and regulating the inflamed pulp microenvironment remain limited. In this study, we investigated the effects of the innate defense regulator peptide IDR-1002 on pulp repair under inflammatory conditions. IDR-1002 showed antibacterial activity against multispecies biofilms, Streptococcus mutans, and Enterococcus faecalis. In human dental pulp stem cells, IDR-1002 reduced LPS-induced expression of IL-6, IL-1β, and TNF-α, attenuated intracellular reactive oxygen species accumulation, and improved wound closure. It also enhanced odontogenic differentiation, as evidenced by increased DSPP and DMP1 expression and enhanced mineral deposition. Exploratory transcriptomic analysis identified enrichment of biological processes potentially associated with IDR-1002 treatment, including extracellular matrix organization, receptor signaling, and tissue repair. To develop a local, microenvironment-responsive delivery system, IDR-1002 was incorporated into an MMP-responsive hydrogel. Biologically active IDR-1002 was released following MMP-9-triggered hydrogel degradation. In a rat pulpitis model, IDR-1002 reduced inflammatory cell infiltration, decreased IL-6 and IL-1β expression, and improved tissue organization at the exposure site. Collectively, these findings demonstrate that IDR-1002 possesses antibacterial, anti-inflammatory, antioxidative, and pro-regenerative properties in the experimental models used in this study and support further investigation of host-regulatory peptides as potential adjunctive agents for biologically based vital pulp therapy.