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

ABSTRACT 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 Cu 2+ for Ca 2+ 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.