State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, China.
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Sichuan, 610041, China.
Biomaterials. 2025 Mar;314:122872. doi: 10.1016/j.biomaterials.2024.122872. Epub 2024 Oct 5.
Periodontal bone defects represent an irreversible consequence of periodontitis associated with reactive oxygen species (ROS). However, indiscriminate removal of ROS proves to be counterproductive for tissue repair and insufficient for addressing existing bone defects. In the treatment of periodontitis, it is crucial to rationally alleviate local ROS while simultaneously promoting bone regeneration. In this study, Zr-based large-pore hierarchical mesoporous metal-organic framework (MOF) nanoparticles (NPs) HMUiO-66-NH were successfully proposed as bifunctional nanomaterials for bone regeneration and ROS scavenging in periodontitis therapy. HMUiO-66-NH NPs demonstrated outstanding biocompatibility both in vitro and in vivo. Significantly, these NPs enhanced the osteogenic differentiation of bone mesenchymal stem cells (BMSCs) under normal and high ROS conditions, upregulating osteogenic gene expression and mitigating oxidative stress. Furthermore, in vivo imaging revealed a gradual degradation of HMUiO-66-NH NPs in periodontal tissues. Local injection of HMUiO-66-NH effectively reduced bone defects and ROS levels in periodontitis-induced C57BL/6 mice. RNA sequencing highlighted that differentially expressed genes (DEGs) are predominantly involved in bone tissue development, with notable upregulation in Wnt and TGF-β signaling pathways. In conclusion, HMUiO-66-NH exhibits dual functionality in alleviating oxidative stress and promoting bone repair, positioning it as an effective strategy against bone resorption in oxidative stress-related periodontitis.
牙周骨缺损是牙周炎相关活性氧（ROS）的不可逆后果。然而，无差别地清除 ROS 被证明对组织修复是适得其反的，且不足以解决现有的骨缺损问题。在牙周炎的治疗中，合理减轻局部 ROS 同时促进骨再生至关重要。在本研究中，Zr 基大孔分级介孔金属有机骨架（MOF）纳米颗粒（NPs）HMUiO-66-NH 被成功提出作为用于牙周炎治疗中骨再生和 ROS 清除的双功能纳米材料。HMUiO-66-NH NPs 在体外和体内均表现出优异的生物相容性。值得注意的是，这些 NPs 在正常和高 ROS 条件下增强了成骨细胞分化，上调了成骨基因表达并减轻了氧化应激。此外，体内成像显示 HMUiO-66-NH NPs 在牙周组织中逐渐降解。局部注射 HMUiO-66-NH 可有效减少牙周炎诱导的 C57BL/6 小鼠的骨缺损和 ROS 水平。RNA 测序强调，差异表达基因（DEGs）主要参与骨组织发育，Wnt 和 TGF-β 信号通路明显上调。总之，HMUiO-66-NH 在缓解氧化应激和促进骨修复方面具有双重功能，为治疗与氧化应激相关的牙周炎中骨吸收提供了一种有效的策略。
