Hu Congjiao, Shi Junqiu, Zhang Fan, Lv Mingchen, Ge Zhenghong, Feng Meiting, Fan Zhen, Liu Danqing, Du Jianzhong, Sun Yao
Shanghai Engineering Research Center of Tooth Restoration and Regeneration & Tongji Research Institute of Stomatology & Department of Implantology, Shanghai Tongji Stomatological Hospital and Dental School, Tongji University, Shanghai, 200072, China.
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-Like Intelligence, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200434, China.
Adv Healthc Mater. 2025 Feb;14(4):e2403817. doi: 10.1002/adhm.202403817. Epub 2024 Dec 20.
Periodontitis is the leading cause of tooth loss in adults. 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)-loaded antioxidative polymersome (RdAP) is designed, which is self-assembled from a mitochondrial-protective and ROS-scavenging block copolymer, poly(ethylene oxide)-block-poly(phenylboronic acid pinacol ester-conjugated polylysine) (PEO-b-P(Lys-PAPE)). The phenylboronic acid pinacol ester (PAPE) segment exhibits excellent ROS-responsive properties, enabling effective ROS scavenging through antioxidant production. Rd significantly enhances mitophagic flux by 2.5-fold 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-treated 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.
牙周炎是成年人牙齿脱落的主要原因。它最初由细菌感染引发，其特征是随后线粒体稳态失调，导致牙周组织持续丧失。线粒体自噬通量是维持线粒体稳态的关键生理机制，在牙周炎中受到损害。此外，活性氧（ROS）释放增加会加剧线粒体损伤。在本研究中，设计了一种负载人参皂苷Rd（Rd）的抗氧化聚合物囊泡（RdAP），它由一种线粒体保护和ROS清除嵌段共聚物聚（环氧乙烷）-嵌段-聚（苯硼酸频哪醇酯共轭聚赖氨酸）（PEO-b-P（Lys-PAPE））自组装而成。苯硼酸频哪醇酯（PAPE）片段具有优异的ROS响应特性，能够通过产生抗氧化剂有效清除ROS。在氧化应激下，Rd可使牙周膜干细胞（PDLSCs）中的线粒体自噬通量显著提高2.5倍。与抗氧化聚合物囊泡一起，RdAP可恢复线粒体稳态并增强PDLSCs的成骨能力，使其更接近健康对照组。在牙周炎小鼠模型中，RdAP治疗组的骨量是未治疗牙周炎组的1.37倍。总体而言，这些发现提出了一种治疗难治性牙周炎的新策略，该策略也可能适用于其他以线粒体稳态失衡为特征的疾病。
