Multifunctional zinc@dTNT/cerium-tannic acid composite system for controlled release of metal micronutrients to enhance bone reconstruction

• Composite controlled-release delivery system: the dumbbell-shaped nanotube confinement, in synergy with metal-phenolic chelation, programs the long-term and sustained release of Zn 2+ and Ce 3+ . • Dual ROS-scavenging: eliminates exogenous ROS and endogenous (mitochondrial-derived) ROS, impeding “ROS-induced ROS loop.” • Comprehensive biological functions: the scaffold optimizes bone reconstruction by modulating the defect microenvironment through antibacterial activity and ROS scavenging, promoting vascularization and osteogenesis. • Hierarchical Material Innovation: We develop a tri-level system integrating 3D-printed scaffolds, dumbbell-shaped nanotubes, and Ce-phenolic coatings, forming a novel composite structure across millimeter-to-nanometer scales and setting a new combinatorial biomaterial paradigm. Effective bone defect repair requires coordinated osteogenesis and angiogenesis while simultaneously combating infection and reactive oxygen species (ROS). However, multifunctional 3D-printed Ti6Al4V scaffolds capable of precisely and differentially releasing bioactive agents remain insufficiently exploration. Given that nanotubes with tailored morphologies exhibit excellent surface modification potential and drug loading capacity, we developed a multifunctional composite controlled-release system (Zn@dTNT/Ce-TA) by coating zinc (Zn)-loaded dumbbell-like titanium dioxide nanotube arrays (dTNT) with cerium (Ce)–tannic acid (TA) metal–phenolic networks (MPNs) to enhance bone reconstruction. This composite scaffold enables sustained and controlled release of Zn and Ce ions, thereby promoting coordinated osteogenesis and angiogenesis while providing antibacterial and antioxidative protection. Furthermore, Zn@dTNT/Ce-TA effectively scavenges both mitochondrial and exogenous ROS, stabilizing the microenvironment at bone defect sites. Overall, this study proposes a promising strategy for reparing critical-sized bone defects and managing ROS-associated bone diseases, offering a valuable direction for future bone tissue engineering.