Exosome-Liposome Hybrid Nanoparticles Enhance Periodontal Regeneration

Aim or purpose: This study developed a novel hybrid nanoparticle system (EXO@Lip-Res) by combining dental pulp stem cell-derived exosomes (DPSC-EXO) with resveratrol-loaded liposomes (Lip-Res) to address the limitations of current periodontitis therapies. The engineered nanoparticles were designed to synergistically enhance antioxidant, anti-inflammatory, and regenerative properties for improved periodontal regeneration. Materials and methods: The EXO@Lip-Res nanoparticles were synthesized through a co-incubation approach and characterized using transmission electron microscopy, dynamic light scattering, and western blot analysis. Comprehensive evaluation included assessment of antioxidant capacity through ABTS, DPPH, H₂O₂, and FRAP assays. Cellular studies investigated nanoparticle uptake efficiency, ROS scavenging capability, and anti-inflammatory effects in PDLSCs and RAW264.7 macrophages. Therapeutic efficacy was evaluated in a rat periodontitis model employing micro-CT imaging, histological examination, and immunohistochemical analysis. Results: The hybrid nanoparticles demonstrated superior stability and bioactivity compared to individual components. EXO@Lip-Res exhibited significantly enhanced ROS scavenging capacity. The nanoparticles markedly reduced pro-inflammatory cytokine levels while promoting macrophage M2 polarization. In vivo studies revealed substantial inhibition of alveolar bone loss and restoration of periodontal architecture. Mechanistic investigations identified suppression of JAK2/STAT3 and p38 signaling pathways as key therapeutic mechanisms. Comprehensive safety assessment confirmed excellent biocompatibility of the nanoparticle system. Conclusions: This study successfully developed an advanced EXO@Lip-Res nanoparticle platform that combines the unique advantages of exosomes and liposomes. The hybrid system represents a promising and safe therapeutic strategy for periodontitis treatment, demonstrating significant potential for clinical translation in periodontal regenerative medicine.