Engineered Exosome Mimetics For Periodontal Tissue Regeneration

This study is expected to provide a new strategy for the clinical application of exosome mimetics (EMs), highlighting EM@[TA-Fe3+] as a promising therapeutic approach for periodontal tissue regeneration. Firstly, bone marrow mesenchymal stem cell (BMSC)-derived EMs were prepared using a progressive extrusion approach, and then were systematically characterized. Furthermore, these EMs are coated with a tannic acid (TA)/Fe3+ coordination network that acts as a protective barrier with antioxidative and antibacterial properties. Finally, the regenerative and anti-inflammatory effects of the TA-Fe3+-engineered EMs were validated in an experimental rat periodontitis model. EMs can enhance production yield while replicating the morphology, structure, and functionality of natural exosomes. TA-Fe3+ coordination network enables EMs to promote stem cell proliferation, migration, osteogenesis, and immunomodulation under inflammatory and oxidative stress conditions. In vivo, the local injection of EM@[TA-Fe3+] effectively suppressed periodontal inflammation and promoted alveolar bone regeneration. These findings advance our understanding of the structural and functional characteristics of EMs and present an efficient strategy for their delivery in periodontal tissue regeneration.