Intelligent Responsive Zeolitic Imidazolate Framework-8@Copper Oxide Nanocomposite 3D-Printed Scaffolds for Efficient Repair of Infected Bone Defects

Multifunctional scaffolds, capable of simultaneous infection control and bone defect repair, provide a robust approach for treating bone defects. However, realizing a scaffold with an optimal balance between antibacterial efficacy and osteogenic ability remains challenging. Herein, by incorporation of zeolitic imidazolate framework-8 encapsulating copper oxide nanoparticles (ZIF-8@CuO), a 3D-printed poly(lactic-<i>co</i>-glycolic acid) nanocomposite scaffold (ZIF-8@CuO/PLGA scaffold) was developed, in which the synergistic effects of ZIF-8 and CuO nanoparticles endowed it with intelligent responsive abilities, including responses to microenvironmental endogenous motivations (pH responsiveness, reactive oxygen species scavenging, and recruiting calcium and phosphorus ions for biomimetic mineralization) and exogenous stimuli (near-infrared responsiveness). Owing to their excellent intelligent responsive abilities, the ZIF-8@CuO/PLGA scaffolds achieved an optimal balance between antibacterial efficacy and osteogenic ability for efficient repair of infected bone defects. In the early stage, by a combination of photothermal therapy, photodynamic therapy, and chemodynamic therapy, the nanocomposite scaffolds demonstrated rapid bacterial eradication. Subsequently, by removing the triggering conditions for bacterial eradication, the ZIF-8@CuO/PLGA scaffolds intelligently switched to enhancing the osteogenic microenvironment through antioxidative action and stimulated angiogenesis and biomimetic bone formation (self-mineralization and osteoinduction), synergistically promoting bone regeneration.