Bioactive Copper‐Doped Natural Hydroxyapatite Quantum Dots/Graphene Oxide Nanocomposites in 3D‐Printed PCL Scaffolds for Superior Osteogenic and Angiogenic Performance in Bone Tissue Engineering

This study introduces a sustainable scaffold designed by integrating copper-doped natural hydroxyapatite quantum dots (Cu-HA QDs) and graphene oxide (GO) into a polycaprolactone (PCL) matrix using 3D printing technology, to address the dual requirements of osteogenesis and angiogenesis in large bone defects. Synchrotron SAXS/WAXS and HR-TEM investigations of the Cu-HA QDs exhibited a highly crystalline hexagonal structure with distinct QD architecture, and core-level HR-XPS analysis confirmed the substitution of Cu²⁺ for Ca²⁺ within the HA lattice. Incorporating Cu-HA-GO nanocomposites significantly improved the physicochemical properties of the PCL scaffolds, including enhanced wettability, accelerated hydrolytic degradation, and increased mechanical stiffness. Under basal culture conditions, the PCL/Cu-HA-GO scaffolds significantly promoted mesenchymal stem cell proliferation, differentiation, and extracellular matrix mineralization. Under basal culture conditions, the PCL/Cu-HA-GO scaffolds significantly stimulated mesenchymal stem cell proliferation, differentiation, and extracellular matrix mineralization. Furthermore, robust osteogenic and angiogenic gene expression was observed, along with pronounced osteocalcin expression and extensive CD31-positive capillary network formation, underscoring the scaffold's unique ability to stimulate bone formation and vascular ingrowth simultaneously. These results present the 3D-printed PCL/Cu-HA-GO scaffolds as a promising, sustainable, dual-functional scaffold with superior osteogenic and angiogenic performance, offering an effective alternative for critical-size bone-defect regeneration.