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Based on the biological rationale provided by clinical single\u2010cell RNA sequencing analysis, we developed an ultrasound\u2010activated piezo\u2010driven Fenton\u2010like system (Fe\u2010BTO) based microsphere (PF@MS). The US triggered piezopotential of the Fe\u2010BTO correlates with ultrasound\u2010associated iron valence modulation to mitigate catalytic bottlenecks linked to Fe\n                    <jats:sup>3<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    \/Fe\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    interconversion, consuming local protons to upregulate MMP from pathological states to the physiological level. This process exhibits self\u2010limiting\u2010like reactivity within the tested dose and ultrasound window, as rising pH acts as a feedback switch to prevent hyperpolarization. We developed a boronate ester\u2010based delivery strategy featuring boronate ester\/sialic\u2010acid\u2010assisted cellular association with mainly clathrin\u2010mediated endocytosis and partial tolerance to ATP depletion. This piezo\u2010Fenton\u2010like mediated mitochondrial modulation rescued impaired autophagic flux (from 8% to 35%) and preserved 89% of the average intervertebral disc height relative to the untreated blank control group in the in vivo rat model. This work provides a mechanically modulated metabolic reprogramming paradigm and highlights the promising application prospect of ultrasound\u2010responsive biomaterials in the treatment of degenerative diseases.\n                  <\/jats:p>","DOI":"10.1002\/adma.74317","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T09:50:00Z","timestamp":1785491400000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ultrasound\u2010Responsive Piezo\u2010Fenton\u2010Like Microspheres for Modulating Mitochondrial Membrane Potential to Alleviate Intervertebral Disc Degeneration"],"prefix":"10.1002","volume":"38","author":[{"given":"Xiaohu","family":"Li","sequence":"first","affiliation":[{"name":"Yangpu Hospital School of Medicine Tongji University Shanghai China"},{"name":"Department of Orthopaedics Shanghai Key Laboratory For Prevention and Treatment of Bone and Joint Diseases Shanghai Institute of Traumatology and Orthopaedics Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai P. 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