Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Jiao Tong University, No. 639, Zhizaoju Rd, Shanghai, 200011, China.
Zhejiang Engineering Research Center for Tissue Repair Materials, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang, 325000, China.
Adv Sci (Weinh). 2024 Aug;11(29):e2403412. doi: 10.1002/advs.202403412. Epub 2024 May 15.
Periodontal disease ranks third among noncommunicable illnesses, behind cancer and cardiovascular disease, and is closely related to the occurrence and progression of various systemic diseases. However, elucidating the processes of periodontal disease and promoting periodontal bone regeneration remains a challenge. Here, quercetin is demonstrated to reduce the oxidative stress state of orofacial mesenchymal stem cells (OMSCs) in vitro and to affect the osteogenic growth of OMSCs through molecular mechanisms that mediate the m6A change in Per1. Nevertheless, the limited therapeutic efficacy of systemic medication and the limitations of local medication resulting from the small, moist, and highly dynamic periodontal environment make it challenging to treat periodontal tissues with medication. Herein, a biosafe injectable hydrogel drug-controlled delivery system is constructed as a bone-enhancing factory and loaded with quercetin to treat oxidative stress injury in periodontal tissues. This drug-carrying system made up of nanoscale bioglass microspheres and a light-cured injectable hydrogel, allows effective drug particle loading and cementation in the dynamic and moist periodontal environment. Furthermore, the system demonstrates the ability to stimulate OMSCs osteogenic differentiation in a Per1-dependent manner, which ultimately promotes periodontal bone repair, suggesting that this system has potential for clinical periodontal therapy.
牙周病在非传染性疾病中排名第三，仅次于癌症和心血管疾病，与各种系统性疾病的发生和发展密切相关。然而，阐明牙周病的发生过程并促进牙周骨再生仍然是一个挑战。在这里，研究表明槲皮素可以减少体外口腔间充质干细胞（OMSCs）的氧化应激状态，并通过介导 Per1 中 m6A 变化的分子机制影响 OMSCs 的成骨生长。然而，由于牙周环境小、湿润且高度动态，全身性药物的治疗效果有限，局部药物的局限性较大，使得药物难以治疗牙周组织。在这里，构建了一种生物安全的可注射水凝胶药物控释系统，作为增强骨的工厂，并负载槲皮素来治疗牙周组织的氧化应激损伤。该载药系统由纳米级生物玻璃微球和光固化可注射水凝胶组成，允许在动态湿润的牙周环境中有效负载和固定药物颗粒。此外，该系统表现出以 Per1 依赖性方式刺激 OMSCs 成骨分化的能力，最终促进牙周骨修复，表明该系统具有临床牙周治疗的潜力。
