Tartaric acid-branched polyethyleneimine carbon dots promote repair of bone defect via osteogenic differentiation

Treating bone defects is a critical challenge in regenerative medicine. Carbon nanomaterials, with their unique physicochemical properties, offer significant potential for enhancing bone regeneration. In this study, we developed tartaric acid (TA)-based carbon dots (CDs) by synthesizing TA with branched polyethyleneimine (bPEI). These TA-bPEI CDs were systematically evaluated to determine their effects on osteogenic differentiation in human bone marrow-derived mesenchymal stem cells (BMSCs) and their capacity to repair calvarial defects in an <i>in vivo</i> model. Characterization of TA-bPEI CDs revealed a size of approximately 10 nm and a positive surface charge. The CDs exhibited fluorescence emission peaks between 464 and 506 nm under excitation wavelengths of 340-440 nm. Cytotoxicity assays demonstrated that TA-bPEI CDs maintained BMSC viability at concentrations up to 250 μg/ml. However, at concentrations of 500 μg/ml and above, apoptosis was induced. Treatment with TA-bPEI significantly enhanced osteogenic differentiation <i>in vitro</i>, as evidenced by increased expression of osteogenic-specific proteins such as Runx2, ALP, OCN and OPN. <i>In vivo</i>, the application of TA-bPEI CDs in a mouse calvarial defect model promoted robust new bone formation, reduced defect gaps, and improved bone morphometric parameters, including bone volume fraction and trabecular thickness. These results suggest that TA-bPEI CDs enhance osteogenesis by directly stimulating osteogenic differentiation and upregulating osteogenesis-specific genes. This study demonstrates the high potential of TA-bPEI CDs as a novel nanomaterial for bone regeneration applications.