大气压常温等离子体对人牙周膜干细胞成骨分化调控机制的研究

Human periodontal ligament stem cells (hPDLSCs) play an important role in maintaining the homeostasis and regenerating defects of periodical tissue. Previous studies showed that reactive oxygen species (ROS) in atmospheric temperature plasma (ARTP) selectively activate and amplify intracellular ROS signaling, as well as promotes the proliferation and differentiation of osteoblasts via increasing the intracellular ROS and reactive nitrogen species (RNS). Our study has previously confirmed that ARTP combined with conventional therapy could effectively promote the regeneration of alveolar bone around the dental implants in Beagle dogs, however, its underlying mechanism has not been fully elucidated. In this light, we hypothesize that ROS derived from ARTP could induce and amplify intracellular ROS signaling of hPDLSCs thus promotes osteogenic differentiation. In order to test this hypothesis, we will evaluate ROS output to improve the ARTP device, and monitor osteogenic differentiation of hPDLSCs treated by ARTP in culture model in vitro and in periodontal bone defect model in vivo. The goal of this study is to explore novel therapeutic targets of periodontal bone regeneration and provide insights of the ARTP-based periodontal regeneration treatments.

人牙周膜干细胞（hPDLSCs）是维持牙周组织动态平衡和缺损修复的关键细胞。研究表明大气压常温等离子体（ARTP）中富含的ROS可以选择性启动和放大ROS信号，即刻和长期增加成骨细胞胞内ROS和RNS，进而促进成骨细胞的增殖和分化。我们的前期研究也已证实ARTP联合常规疗法可有效促进Beagle犬炎症种植体周围骨组织的再生，但其作用机制尚不明确。为此，我们提出假说：ARTP中ROS可引发和扩增hPDLSCs胞内ROS信号并促进其成骨分化。为了验证这一假说，我们将通过改进前期ARTP装置并对其产生的ROS进行诊断，然后利用ARTP处理hPDLSCs体外培养模型及牙周骨缺损动物模型，探究ARTP促进hPDLSCs成骨分化可能的体外、体内机制，为寻找特异性的牙周骨再生治疗靶点、探索基于ARTP技术的牙周再生手段提供新的思路。

人牙周膜干细胞（hPDLSCs）是维持牙周组织动态平衡和缺损修复的关键细胞。研究表明大气压常温等离子体（ARTP）中富含的ROS可以选择性启动和放大ROS信号，即刻和长期增加成骨细胞胞内ROS和RNS，进而促进成骨细胞的增殖和分化。我们前期研究已证实ARTP联合常规疗法可有效促进Beagle犬炎症种植体周围骨组织的再生，但其作用机制尚不明确。在前期研究基础上，我们在本项目中自主成功研制了更适合牙周病治疗的大气压常温等离子体装置，实现了工作端可直接插入牙周袋内进行放电处理的这一创新性技术突破，并对其产生的等离子体特别是其中ROS基本特性进行了诊断；再通过利用ARTP处理hPDLSCs的体外实验和SD大鼠牙周骨缺损的体内实验验证了ARTP促进牙周组织再生的作用，分析了ROS在其中可能起到的重要作用及其机制，为口腔临床寻找牙周炎特异性的治疗靶点、探索牙周再生手段提供新的思路及实验依据，进而扩展大气压常温等离子体在口腔医学其他常见疾病防治领域的应用，具有重要的学术价值、临床治疗意义和广阔应用前景。