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We engineered a biomimetic piezoelectric hydrogel (CMB Gel) by embedding chondrocyte membrane\u2010camouflaged, CAP peptide\u2010grafted barium titanate nanoparticles into a dynamic borate ester\u2010crosslinked network, enabling active cartilage targeting and on\u2010demand ultrasound activation. Under ultrasound, the piezoelectric component generates local electrical signals, triggering Ca\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    influx via voltage\u2010gated calcium channels and AMPK activation. Activated AMPK inhibits the mTOR pathway, inducing epigenetic reprogramming via H3K27 acetylation at the GATD3A promoter. Upregulated GATD3A stabilizes TFAM and enhances PINK1\/Parkin\u2010mediated mitophagy, clearing damaged mitochondria and reducing oxidative stress in chondrocytes. In a mouse destabilization of medial meniscus model, ultrasound\u2010activated CMB Gel attenuated cartilage degradation, osteophyte formation, and synovitis. Its therapeutic efficacy was validated in human OA cartilage explants. This work presents a multifunctional targeted delivery platform that converts mechanical energy into epigenetic signals to restore cellular homeostasis, offering a promising strategy for OA and other mechanosensitive degenerative diseases.\n                  <\/jats:p>","DOI":"10.1002\/advs.76140","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T14:47:03Z","timestamp":1781621223000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ultrasound\u2010Activatable Piezoelectric Hydrogel Reprograms Mitochondrial Epigenetics for Osteoarthritis Therapy via the mTOR\/GATD3A Axis"],"prefix":"10.1002","author":[{"given":"Hui","family":"Zheng","sequence":"first","affiliation":[{"name":"College of Materials Science and Engineering Hunan University  P. R. 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