Regulation of bone microenvironment (BME) including innate pH values and metal ions affects cellular functions and activities of osteoblasts and osteoclasts, thereby significantly influencing the process of bone regeneration. How to achieve multiple effective regulations of the BME through cascade effects via facile material design and fabrication to significantly facilitate osteogenesis remains a challenge. Herein, a facilely-designed resorbable guided bone regeneration membrane (PCL/DEX@Ca-Zol) based on a drug-loaded metal-organic framework is reported. Thereinto, calcium ions, zoledronic acid, and dexamethasone embedded in the membrane can be responsively released specifically inside bone defect in an acid-triggered manner to synergistically regulate BME by neutralization of pH value, enhancement of osteogenic differentiation and mineralization, and inhibition of osteoclasts in one-go. Along with polycaprolactone as a structural support in the membrane for bone regeneration with fully utilized components of the composite membrane material, enhances bone regeneration with minimized side effects is accordingly achieved with the assistance of effective modulation of BME through multiple cascade effects.
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