GSP-Functionalized Sc Exosomes As Neuromodulation Vehicles For Diabetic Periodontitis

The purpose of this study was to evaluate the effect of grape seed polyphenol -functionalized Schwann cell-derived exosomes (GSP@SC Exo) nanoparticles on diabetic periodontal regeneration. The primary SC exosomes were isolated through subsequent ultracentrifugation, and then identified by TEM, Western blot, and nanoparticle tracking analysis. After incubation, GSP formed a polyphenolic coating on the surface of SC exosomes through oxidative polymerization and non-covalent interactions. The morphology, radical scavenging ability, and stability of GSP@BMSC Exo system were characterized by TEM, DPPH and ABTS analyses, and BCA methods respectively. Macrophage polarization and pro-inflammatory factors were investigated by immunofluorescence staining and ELISA in vitro. The cell migration and tube formation of HUVECs, osteogenic differentiation of hPDLSCs were test as well. Moreover, Sprague-Dawley (SD) rats were induced with the combination of Type 1 diabetes mellitus and periodontitis through intraperitoneal administration of streptozotocin and ligation with silk thread. Then micro CT, histological, immunohistochemical, and immunofluorescence analyses were performed to assess periodontal regeneration. The GSP-cloaked SC Exo (GSP@SC Exo) system showed antioxidant and antibacterial activities. Moreover, these GSP@SC Exo nanoparticles significantly induced axonal growth of dorsal root ganglia (DRG) explants, M2 polarization of macrophages, tube formation of HUVECs, and hPDLSCs osteogenic differentiation in vitro. Moreover, the diabetic periodontal destruction was alleviated significantly by nerve regeneration, immunomodulation, neovascularization, and alveolar bone formation in vivo. This study provides a facile and effective neuroregulatory strategy for guiding the diabetes periodontitis treatment in clinical applications.