“Small dots, multiple functions”: unveiling the veil of a bioactive quercetin carbon dot and its multifaceted antibacterial and osteogenesis mechanisms for infectious bone defect repair

In infectious bone injury microenvironments, an ideal material should possess antibacterial, osteogenic, and angiogenic functions simultaneously. However, relying on a single material to achieve the above goals is challenging. In this study, a quercetin carbon dot (QCD) is developed with multiple functions. The structure of QCDs are analysed, and the results of molecular docking and cellular thermal-shift assay confirmed RTKs as potential targets. Then the QCDs are incorporated into methacryloylated polyglutamic acid grafted with aminophenylboronic acid hydrogel with reactive oxygen species-responsive properties. The QCDs can activate the Rap1 pathway in bone marrow mesenchymal stem cells, which can promote angiogenesis and translocation of β-catenin to promote osteogenesis. Moreover, the Rap1 can also activate PI3K-AKT pathway related to cell proliferation. For killing bacteria, the QCDs inhibit the gene expression of dapE, phoP, and secA2, which can disrupt the bacterial wall, inhibit drug resistance, and interfere with energy metabolism. This study reveals the chemical structure of QCDs, and finds they can interact with RTKs and thus activate the Rap1 signaling pathway to promote bone regeneration and kill bacteria by destroying their walls and interfering with energy metabolism, thus providing insights for developing a simplified component with multiple functions for repairing infectious bone defects.