Lactobacillus Plantarum -Derived Extracellular Vehicles Promote Injured Pulp Repair

This study pioneers the therapeutic application of Lactobacillus plantarum-derived extracellular vesicles (LEVs) for pulpitis resolution, leveraging their potent anti-inflammatory properties and unrecognized regenerative potential in dental pulp repair. LEVs were characterized by nanoparticle tracking and TEM, and their roles in inflammatory response, proliferation and odontogenic differentiation of LPS-stimulated human dental pulp stem cells (hDPSCs) were assessed through qRT-PCR, alkaline phosphatase staining, alizarin red staining and western blot. A novel LEVs-loaded GelMA/nanoclay hydrogel (Gel/Nano-EV) was engineered for controlled delivery and tested in rat pulp injury models. LEVs (10 μg/mL) significantly suppressed proinflammatory cytokines (TNF-α, IL-6 and Il-1b), enhancing odontogenic differentiation markers (DSPP and DMP-1 and mineralized tissue of LPS-induced hDPSCs. Gel/Nano-EV demonstrated great biocompatible, biodegradable, injectable, excellent mechanical properties and sustained LEVs release (>15 days). In vivo, Gel/Nano-EV efficiently induced dentin bridge formation in injured pulp, which is about equivalent to conventional pulp capping materials (Ca(OH)2). LEVs as dual-functional nanotherapeutics that reverse inflammatory microenvironment and reactivate dentinogenic programming, while the engineered hydrogel platform enables precision regenerative medicine for pulpitis management. These findings suggests that LEVs maybe present a promising therapeutic strategy for both preventing and managing pulpitis.