Xiu Ziliang, Zhu Yujing, Li Xiaofeng, Jiang Xiaoxi, Feng Yunru, He Li, Li Chunhui, Cai Rui, Tao Gang
Oral & Maxillofacial Reconstruction and Regeneration of Luzhou Key Laboratory, The Affiliated Stomatological Hospital, Southwest Medical University, Luzhou 646000, China.
Department of Periodontics & Oral Mucosal Diseases, The Affiliated Stomatological Hospital, Southwest Medical University, Luzhou 646000, China.
Theranostics. 2025 Mar 3;15(9):3750-3780. doi: 10.7150/thno.107793. eCollection 2025.
Pathogenic bacteria and activated immune cells in periodontal tissues continuously generate reactive oxygen species (ROS) and inflammatory mediators, creating an oxidative stress microenvironment that causes damage to cells and tissues. Antimicrobial strategies and ROS scavenging are crucial for treating periodontitis. This study encapsulated iron-curcumin nanoparticles (Fe-Cur NPs) within GelMA microspheres using microfluidic technology. The microsphere surface was then modified with a polydopamine (PDA) layer, and minocycline hydrochloride (MH) was attached to it to form multifunctional composite microspheres (GM@Fe-Cur/PDA/MH). The GM@Fe-Cur/PDA/MH microspheres exhibited excellent adhesion, allowing them to remain in periodontal pockets for prolonged periods to maintain their functionality. Benefiting from the photothermal properties of PDA combined with MH, these microspheres effectively kill bacteria and mitigate excessive immune responses. Additionally, they regulate the M1/M2 polarization of macrophages, suppress the expression of inflammatory factors, and promote osteogenic protein expression under oxidative stress conditions . In a rat model of periodontitis, GM@Fe-Cur/PDA/MH effectively controlled inflammation progression and reduced alveolar bone loss. Further studies indicated that GM@Fe-Cur/PDA/MH may promote ROS scavenging by modulating the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway while inhibiting the activation of the nod-like receptor protein-3 (NLRP3) inflammasome. In summary, GM@Fe-Cur/PDA/MH represents an effective therapeutic approach that integrates antibacterial, antioxidant, anti-inflammatory, and bone loss mitigation properties, demonstrating significant potential for application in the treatment of periodontitis.
牙周组织中的致病细菌和活化的免疫细胞持续产生活性氧(ROS)和炎症介质,形成氧化应激微环境,对细胞和组织造成损伤。抗菌策略和ROS清除对于治疗牙周炎至关重要。本研究利用微流控技术将铁-姜黄素纳米颗粒(Fe-Cur NPs)包裹在甲基丙烯酰化明胶(GelMA)微球内。然后用聚多巴胺(PDA)层修饰微球表面,并在其上附着盐酸米诺环素(MH),形成多功能复合微球(GM@Fe-Cur/PDA/MH)。GM@Fe-Cur/PDA/MH微球表现出优异的黏附性,使其能够长时间留在牙周袋中以维持其功能。受益于PDA与MH相结合的光热特性,这些微球能有效杀灭细菌并减轻过度的免疫反应。此外,它们在氧化应激条件下调节巨噬细胞的M1/M2极化,抑制炎症因子的表达,并促进成骨蛋白表达。在牙周炎大鼠模型中,GM@Fe-Cur/PDA/MH有效控制了炎症进展并减少了牙槽骨吸收。进一步研究表明,GM@Fe-Cur/PDA/MH可能通过调节核因子红细胞2相关因子2(Nrf2)信号通路促进ROS清除,同时抑制NOD样受体蛋白3(NLRP3)炎性小体的激活。总之,GM@Fe-Cur/PDA/MH代表了一种整合抗菌、抗氧化、抗炎和减轻骨吸收特性的有效治疗方法,在牙周炎治疗中显示出巨大的应用潜力。