Second Clinical Division, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, No. 22, Zhongguancun South Avenue, Haidian District, Beijing, 100081, People's Republic of China.
Center for Digital Dentistry, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, No. 22, Zhongguancun South Avenue, Haidian District, Beijing, 100081, People's Republic of China.
J Transl Med. 2024 Nov 2;22(1):992. doi: 10.1186/s12967-024-05808-1.
When inflammation occurs in periodontal tissues, a dynamic cellular crosstalk interacts between gingival fibroblasts and bone marrow mesenchymal stem cells (BMSCs), which plays a crucial role in the biological behaviour and differentiation of the cells. Recently, flavonoids are increasingly recognized for their therapeutic potential in modulating inflammation and osteogenic differentiation. Owing to their varied molecular structures and mechanisms, there are more needs that flavonoid compounds should be identified by extensive screening. However, current drug research mostly relies on static, single-type cell cultures. In this study, an innovative bionic microfluidic chip system tailored for both soft and hard tissues was developed to screen for flavonoids suitable for treating periodontitis.
This study developed a microfluidic system that bionically simulates the soft and hard structures of periodontal tissues. Live/dead staining, reactive oxygen species (ROS) staining, and RT-qPCR analysis were employed. These techniques evaluated the effects of flavonoid compounds on the levels of inflammatory factors and ROS contents in HGF and HBMSC under LPS stimulation. Additionally, the impact of these compounds on osteogenic induction in HBMSC and the exploration of the underlying mechanisms were assessed.
The microfluidic chip used in this study features dual chambers separated by a porous membrane, allowing cellular signal communication via bioactive factors secreted by cells in both layers under perfusion. The inflammatory response within the chip under LPS stimulation was lower compared to individual static cultures of HGF and HBMSC. The selected flavonoids-myricetin, catechin, and quercetin-significantly reduced cellular inflammation, decreased ROS levels, and enhanced osteogenic differentiation of BMSCs. Additionally, fisetin, silybin, and icariside II also demonstrated favorable outcomes in reducing inflammation, lowering ROS levels, and promoting osteogenic differentiation through the Wnt/β-catenin pathway.
The bionic microfluidic chip system provides enhanced capabilities for drug screening and evaluation, delivering a more precise assessment of drug efficacy and safety compared to traditional in vitro methods. This study demonstrates the efficacy of flavonoids in influencing osteogenic processes in BMSCs primarily through the Wnt/β-catenin pathway. These results uncover the potential of flavonoids as therapeutic medicine for treating periodontitis, meriting further research and development.
当牙周组织发生炎症时，牙龈成纤维细胞和骨髓间充质干细胞（BMSCs）之间会发生动态的细胞串扰，这在细胞的生物学行为和分化中起着至关重要的作用。最近，类黄酮因其在调节炎症和成骨分化方面的治疗潜力而越来越受到关注。由于其分子结构和机制的多样性，需要通过广泛的筛选来确定类黄酮化合物。然而，目前的药物研究主要依赖于静态的、单一类型的细胞培养。在这项研究中，开发了一种针对软硬组织的仿生微流控芯片系统，用于筛选治疗牙周炎的类黄酮。
本研究开发了一种仿生微流控系统，该系统模拟了牙周组织的软硬结构。采用活/死染色、活性氧（ROS）染色和 RT-qPCR 分析评估类黄酮化合物对 LPS 刺激下 HGF 和 HBMSC 中炎症因子水平和 ROS 含量的影响。此外，还评估了这些化合物对 HBMSC 成骨诱导的影响，并探讨了其潜在机制。
本研究中使用的微流控芯片具有由多孔膜分隔的两个腔室，允许通过两层细胞分泌的生物活性因子进行细胞信号通讯。与 HGF 和 HBMSC 的单独静态培养相比，芯片在 LPS 刺激下的炎症反应较低。所选的类黄酮——杨梅素、儿茶素和槲皮素——显著降低了细胞炎症，降低了 ROS 水平，并增强了 BMSCs 的成骨分化。此外，非瑟酮、水飞蓟宾和淫羊藿苷 II 也通过 Wnt/β-catenin 通路在降低炎症、降低 ROS 水平和促进成骨分化方面表现出良好的效果。
仿生微流控芯片系统为药物筛选和评估提供了更强的能力，与传统的体外方法相比，能够更精确地评估药物的疗效和安全性。本研究表明，类黄酮主要通过 Wnt/β-catenin 通路影响 BMSCs 的成骨过程。这些结果揭示了类黄酮作为治疗牙周炎的治疗药物的潜力，值得进一步的研究和开发。
