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Bioinspired, Mitochondria-Targeted Single-Atom Nanozyme Enhances Bone Regeneration by Reprogramming Stem Cell Energy

Yuwen Wang1, Xinzhi Liang2, Tiandi Xiong1,3

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Advanced Materials (Deerfield Beach, Fla.)
|April 7, 2026
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Summary
This summary is machine-generated.

Mitochondria are vital for bone repair. Scientists created a nanozyme that targets mitochondria, boosting stem cell energy and significantly enhancing bone regeneration in rats.

Keywords:
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Area of Science:

  • Biomaterials Science
  • Regenerative Medicine
  • Nanotechnology

Background:

  • Mitochondrial dysfunction impairs stem cell function, hindering effective bone regeneration.
  • Mitochondrial Complex IV (cytochrome c oxidase, CcO) is critical for cellular energy production via the electron transport chain and ATP synthesis.

Purpose of the Study:

  • To develop a novel nanozyme that mimics CcO activity and targets mitochondria to restore cellular energy metabolism for enhanced bone regeneration.
  • To evaluate the efficacy of the TPP-DMSN-Fe/Cu nanozyme in promoting stem cell osteogenesis in vitro and bone healing in vivo.

Main Methods:

  • Development of a dendritic mesoporous silica nanoparticle (DMSN)-based nanozyme, TPP-DMSN-Fe/Cu, incorporating iron and copper single atoms to mimic CcO's catalytic center.
  • Modification of the nanozyme with a mitochondria-targeting agent (triphenylphosphonium, TPP).
  • In vitro assessment of nanozyme colocalization with mitochondria, mitochondrial function, cellular energy metabolism, and stem cell osteogenesis.
  • In vivo evaluation of the nanozyme's effect on bone regeneration in critical-sized bone defects in rats.

Main Results:

  • TPP-DMSN-Fe/Cu nanozymes successfully localized in mitochondria, enhancing mitochondrial function and promoting stem cell osteogenesis in vitro.
  • In vivo studies showed a 177% increase in bone volume and a 12% increase in mineral density in rats with critical-sized bone defects after 4 weeks of treatment.
  • The nanozyme effectively regulated cellular energy metabolism, contributing to accelerated bone healing.

Conclusions:

  • Bioinspired, mitochondria-targeting TPP-DMSN-Fe/Cu nanozymes are a promising therapeutic strategy for accelerating bone regeneration.
  • Restoring cellular energy metabolism through targeted nanozymes offers a novel approach to address bone defects.
  • This study highlights the potential of nanozyme technology in regenerative medicine for improving bone healing outcomes.