CGA–Eu nanozyme-functionalized 3D-printed scaffolds accelerate osteoporotic bone regeneration via ROS scavenging and angio-osteogenic modulation

Impaired bone regeneration in osteoporosis primarily stems from a local pathological microenvironment characterized by high levels of reactive oxygen species (ROS), which severely inhibits osteogenic differentiation and angiogenesis. To address this challenge, this study engineered a 3D-printed multifunctional composite scaffold consisting of an α-tricalcium phosphate/zinc oxide (α-TCP/ZnO) matrix loaded with chlorogenic acid–europium (CGA–Eu) metal-phenolic network nanoparticles. The incorporation of ZnO effectively buffered the acidity generated by α-TCP degradation, thereby maintaining a physiological pH environment favorable for regeneration. Furthermore, CGA–Eu endowed the scaffold with potent antioxidant capacity, enabling it to efficiently scavenge excessive ROS and significantly alleviate oxidative damage in vitro. Biological evaluations confirmed that the sustained release of Eu3+, Zn2+, and CGA cooperatively promoted osteogenic differentiation of bone marrow mesenchymal stem cells and angiogenic activity in human umbilical vein endothelial cells. In an ovariectomized rat cranial defect model, the composite scaffold effectively accelerated bone mass accumulation and enhanced angiogenesis. In conclusion, this dual microenvironment-regulating strategy, which integrates pH buffering, ROS scavenging, and sustained osteo-angiogenic ion delivery, offers a promising scaffold design for osteoporotic bone defect repair.