Metformin carbon dots-based osteogenic and protein delivery system to promote bone regeneration in periodontitis.

The chronic inflammation in periodontitis suppresses the osteogenic potential of human periodontal ligament stem cells (hPDLSCs), posing a significant challenge to endogenous bone regeneration. To address this, we developed an osteogenic and protein-delivery composite hydrogel system based on metformin carbon dots (MCDs) to enhance the osteogenic potential of hPDLSCs under inflammatory conditions. We successfully synthesized a novel Gel/MCDs@IGF-1 composite hydrogel (Gel) that exhibited excellent biocompatibility and sequentially released MCDs and insulin-like growth factor 1 (IGF-1). First, MCDs were synthesized using a one-step hydrothermal method. MCDs promote the osteogenic differentiation of hPDLSCs under lipopolysaccharide (LPS)-induced inflammatory conditions by activating the PI3K/AKT signaling pathway, and alleviate inflammation. Next, MCDs and IGF-1 were assembled into MCDs@IGF-1 complexes through supramolecular interactions, facilitating efficient IGF-1 delivery and reducing its degradation by trypsin. Furthermore, in vitro and in vivo studies demonstrated that the Gel/MCDs@IGF-1 composite hydrogel effectively recruited stem cells, exerted early anti-inflammatory effects, increased the osteogenesis of hPDLSCs under inflammatory conditions, and significantly promoted alveolar bone regeneration in a Sprague-Dawley (SD) rat model of periodontitis. In conclusion, MCDs, with their dual roles in promoting osteogenesis and protein delivery, are a promising candidate nanoplatform for periodontitis therapy. Additionally, the MCDs-based sequential release hydrogel system presents a novel material strategy for the treatment of periodontitis.