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The normal mitochondrial function in stem cells is crucial for effective bone regeneration. The mitochondrial complex IV (cytochrome c oxidase, CcO) plays a key role in maintaining the activity of the electron transport chain and ATP synthesis. To address mitochondrial dysfunction related to bone defects, we developed a CcO mimetic nanozyme based on dendritic mesoporous silica nanoparticles (DMSN), named TPP-DMSN-Fe/Cu. This nanozyme combines iron and copper monatomic species to simulate the catalytic center of CcO and is modified with the mitochondrial-targeting agent TPP. In vitro, the TPP-DMSN-Fe/Cu nanozyme localizes with mitochondria, enhances mitochondrial function, effectively regulates cellular energy metabolism, and promotes stem cell bone formation. In vivo, the TPP-DMSN-Fe/Cu nanozyme significantly enhances bone regeneration. Four weeks after treatment, the bone volume in the severely bone-deficient area of rats increased by 177%, and the mineral density increased by 12%. Overall, these findings indicate that the bio-inspired mitochondrial-targeting TPP-DMSN-Fe/Cu nanozyme has a strong potential to accelerate bone regeneration by regulating cellular energy metabolism. This research was published in Advanced Materials under the title "Bioinspired, Mitochondria-Targeted Single-Atom Nanozyme Enhances Bone Regeneration by Reprogramming Stem Cell Energy Metabolism".
References:
DOI: 10.1002/adma.202522108
