Mcds-Based Osteogenic And Protein-Delivery System For Periodontal Regeneration

To develop an osteogenic and protein-delivery composite hydrogel system based on metformin carbon dots (MCDs) that enhances osteogenic potential of human periodontal ligament stem cells (hPDLSCs) under inflammatory conditions and promotes endogenous bone regeneration in periodontitis. MCDs were synthesized via a one-step hydrothermal method. The Gel/MCDs@IGF-1 hydrogel was developed by incorporating insulin-like growth factor 1 (IGF-1) via supramolecular interactions. The biocompatibility was assessed using CCK-8 assay, Transwell-migration assay, live/dead-cell-staining. The osteogenic potential was evaluated through ALP and Alizarin-Red-S staining, qRT-PCR, immunofluorescence staining (IF), and western blotting (WB). RNA sequencing and WB were performed to investigate the underlying mechanisms. In vivo, IF, immunohistochemistry, Micro-CT, H&E staining and Masson’s staining were performed in rat periodontitis models. The Gel/MCDs@IGF-1 hydrogel with good biocompatibility was successfully synthesized, enabling sequential release of MCDs and IGF-1. MCDs promoted osteogenic differentiation of hPDLSCs via the PI3K/AKT pathway and alleviated inflammation. The MCDs@IGF-1 complex enhanced IGF-1 delivery and reduced its enzymatic degradation. In vitro and vivo experiments demonstrated that the composite hydrogel system increased ALP activity and calcium-nodule formation, reduced effectively attachment loss in rat periodontitis, suppressed TNF-α level, and upregulated levels of CD90 and osteogenesis-related genes and proteins. The MCDs-based osteogenic and protein delivery system recruited effectively stem cells, exerted early anti-inflammatory effects, and promoted periodontal bone regeneration, offering a novel strategy for treatment of periodontitis.