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However, there is still no effective method to cure chronic inflammation\u2010associated bone diseases by physiologically restoring the function of mitochondria and MSCs. Herein, it is first found that chronic inflammation leads to excess Ca<jats:sup>2+<\/jats:sup> transfer from the endoplasmic reticulum to mitochondria, which causes mitochondrial calcium overload and further damage to mitochondria. Furthermore, damaged mitochondria continuously accumulate in MSCs due to the inhibition of mitophagy by activating the Wnt\/<jats:italic>\u03b2<\/jats:italic>\u2010catenin pathway under chronic inflammatory conditions, impairing the differentiation of MSCs. Based on the mechanistic discovery, intracellular microenvironment (esterase and low pH)\u2010responsive nanoparticles are fabricated to capture Ca<jats:sup>2+<\/jats:sup> around mitochondria in MSCs to regulate MSC mitochondrial calcium flux against mitochondrial dysfunction. Furthermore, the same nanoparticles are able to deliver siRNA to MSCs to inhibit the Wnt\/<jats:italic>\u03b2<\/jats:italic>\u2010catenin pathway and regulate mitophagy of the originally dysfunctional mitochondria. These precision\u2010engineered nanoparticles, referred to as \u201cnanorepairers,\u201d physiologically restore the function of mitochondria and MSCs, resulting in effective therapy for periodontitis and osteoarthritis. The concept can potentially be expanded to the treatment of other diseases via mitochondrial quality control intervention.<\/jats:p>","DOI":"10.1002\/advs.202103839","type":"journal-article","created":{"date-parts":[[2021,12,11]],"date-time":"2021-12-11T03:44:28Z","timestamp":1639194268000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":84,"title":["Nanorepairers Rescue Inflammation\u2010Induced Mitochondrial Dysfunction in Mesenchymal Stem Cells"],"prefix":"10.1002","volume":"9","author":[{"given":"Qiming","family":"Zhai","sequence":"first","affiliation":[{"name":"State Key Laboratory of Military Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; Shaanxi International Joint Research Center for Oral Diseases Center for Tissue Engineering School of Stomatology Fourth Military Medical University  Xi'an Shaanxi 710032 China"},{"name":"Department of Orthodontics School of Stomatology Fourth Military Medical University  Xi'an Shaanxi 710032 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering Shaanxi Key Laboratory of Energy Chemical Process Intensification Institute of Polymer Science in Chemical Engineering School of Chemical Engineering and Technology Xi'an Jiao Tong University  Xi'an Shaanxi 710049 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongdong","family":"Fei","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Military Stomatology &amp; 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