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Initially triggered by bacterial infection, it is characterized by subsequent dysregulation of mitochondrial homeostasis, leading to ongoing loss of periodontal tissue. Mitophagic flux, a critical physiological mechanism for maintaining mitochondrial homeostasis, is compromised in periodontitis. Additionally, increased release of reactive oxygen species (ROS) exacerbates mitochondrial damage. In this study, a ginsenoside Rd (Rd)\u2010loaded antioxidative polymersome (RdAP) is designed, which is self\u2010assembled from a mitochondrial\u2010protective and ROS\u2010scavenging block copolymer, poly(ethylene oxide)\u2010<jats:italic>block<\/jats:italic>\u2010poly(phenylboronic acid pinacol ester\u2010conjugated polylysine) (PEO<jats:sub>113<\/jats:sub>\u2010<jats:italic>b<\/jats:italic>\u2010P(Lys\u2010PAPE)<jats:sub>60<\/jats:sub>). The phenylboronic acid pinacol ester (PAPE) segment exhibits excellent ROS\u2010responsive properties, enabling effective ROS scavenging through antioxidant production. Rd significantly enhances mitophagic flux by 2.5\u2010fold in periodontal ligament stem cells (PDLSCs) under oxidative stress. Together with the antioxidative polymersome, RdAPs restore mitochondrial homeostasis and enhance the osteogenic capacity of PDLSCs, bringing it closer to that of healthy controls. In a mouse model of periodontitis, the bone mass in the RdAP\u2010treated group is 1.37 times greater than that in the untreated periodontitis group. Overall, the findings propose a novel strategy for addressing refractory periodontitis, which may also be applicable to other diseases characterized by mitochondrial homeostasis imbalance.<\/jats:p>","DOI":"10.1002\/adhm.202403817","type":"journal-article","created":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T03:01:48Z","timestamp":1734663708000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Ginsenoside Rd\u2010Loaded Antioxidant Polymersomes to Regulate Mitochondrial Homeostasis for Bone Defect Healing in Periodontitis"],"prefix":"10.1002","volume":"14","author":[{"given":"Congjiao","family":"Hu","sequence":"first","affiliation":[{"name":"Shanghai Engineering Research Center of Tooth Restoration and Regeneration &amp; Tongji Research Institute of Stomatology &amp; Department of Implantology Shanghai Tongji Stomatological Hospital and Dental School Tongji University  Shanghai 200072 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junqiu","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Gynaecology and Obstetrics Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation Clinical Research Center for Anesthesiology and Perioperative Medicine Translational Research Institute of Brain and Brain\u2010Like Intelligence Shanghai Fourth People's Hospital School of Medicine Tongji University  Shanghai 200434 China"},{"name":"Department of Polymeric Materials School of Materials Science and Engineering Tongji University  4800 Caoan Road Shanghai 201804 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanghai Engineering Research Center of Tooth Restoration and Regeneration &amp; 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