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To address mitochondrial dysfunction associated with bone defects, we developed a dendritic mesoporous silica nanoparticle (DMSN)\u2010based, CcO\u2010mimetic nanozyme, named triphenylphosphonium (TPP)\u2010DMSN\u2010Fe\/Cu. The nanozyme incorporated iron and copper single atoms to mimic the catalytic center of CcO and is modified with the mitochondria\u2010targeting agent TPP. In vitro, TPP\u2010DMSN\u2010Fe\/Cu nanozymes colocalized with mitochondria and enhanced mitochondrial function, effectively regulating cellular energy metabolism and promoting stem cell osteogenesis. In vivo, TPP\u2010DMSN\u2010Fe\/Cu nanozymes resulted in significantly enhanced bone regeneration compared to the control, resulting in a 177% increase in bone volume and a 12% increase in mineral density at critical\u2010sized bone defects in rats after 4 weeks of treatment. 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