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However, reconstituting ETC\u2010associated mitochondrial bioenergetics in situ to overcome this energy restriction remains challenging. In this study, a mitochondrial hydrogen\u2010supply system (EMHS) is developed that attenuates senescence\u2010associated phenotypes in the aged bone regenerative niche and promotes skeletal healing in aging via proton\u2010coupled electron transfer (PCET). It has been demonstrated that the active hydrogen generated by EMHS infiltrates mitochondria in senescent cells, enabling the paired delivery of proton\u2013electron equivalents to restore ETC function. This mitochondrial functional recovery is accompanied by reduced mitochondrial reactive oxygen species (ROS) and improved oxidative phosphorylation (OXPHOS) capacity, which expands the functional mitochondrial pool. EMHS restores the osteogenic potential of bone marrow mesenchymal stem cells (BMSCs), enhances endothelial angiogenic capacity, and biases neutrophils toward a pro\u2010repair phenotype. Remarkably, following systemic administration, EMHS preferentially accumulates in bone and promotes bone\u2010vascular coupled regeneration in aged mice with bone defects. Overall, our findings introduce a small\u2010molecule drug\u2010free nanotherapeutic strategy that maintains a functional mitochondrial pool with potential to alleviate cellular aging and age\u2010related diseases.<\/jats:p>","DOI":"10.1002\/adma.74133","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T08:35:10Z","timestamp":1784536510000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["PCET\u2010Inspired Nanoparticles Enable Paired Proton\u2010Electron Delivery to Restore Mitochondrial Electron Transport and Regenerate Bone During Aging"],"prefix":"10.1002","volume":"38","author":[{"given":"Kelei","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery The Second Affiliated Hospital Zhejiang University School of Medicine  Hangzhou P. R. China"},{"name":"Orthopedics Research Institute Zhejiang University  Hangzhou P. R. 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