Yu Yameng, Zhao Xiwen, Zheng Yufeng, Xia Dandan, Liu Yunsong
Department of Dental Materials, Peking University School and Hospital of Stomatology, Beijing, 100081, China; National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental Materials, Beijing, 100081, China.
National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental Materials, Beijing, 100081, China; Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, China.
Biomaterials. 2026 Feb;325:123588. doi: 10.1016/j.biomaterials.2025.123588. Epub 2025 Jul 29.
Colonization of pathogenic microorganism is the initiating factor of periodontitis, inflammatory-induced imbalance of reductant-oxidant homeostasis is the leading cause of alveolar bone defects. Herein, core-shell structured nanohybrids with antibacterial, antioxidative and osteogenic properties were constructed by in situ growth of ZIF-8 nanocrystals onto cerium oxide nanoparticles (CeO@ZIF-8). The Ce/Ce ratio can be manipulated via regulating the ZIF-8 shell thickness. The shell thickness increased with elevated concentration of Zn that coordinated with organic linker in the synthesis process, leading to enhanced Ce/Ce ratio in CeO@ZIF-8, which further promoted its antioxidative enzyme mimetic activities as well as osteogenic property. In vitro, CeO@ZIF-8 exhibited excellent antibacterial activities, provided cellular protective effect under oxidative stress state, and facilitated osteogenic differentiation. In vivo, CeO@ZIF-8 could alleviated bacterial infection induced inflammation response and promoted alveolar bone regeneration. The underlying mechanism was explored via bioinformatic analysis, which indicated that CeO@ZIF-8 promoted the expression of copper-zinc superoxide dismutase (SOD1) via upregulating oxidoreductase activity, so that to relive the oxidative stress and upregulate the expression of osteogenesis related genes and proteins. The above findings indicated that CeO@ZIF-8 could simultaneously achieve bacteriostasis, ROS scavenging and osteogenesis, so that to completely fulfill the therapeutic demand in the treatment of periodontitis.
致病微生物的定植是牙周炎的起始因素,炎症诱导的氧化还原稳态失衡是牙槽骨缺损的主要原因。在此,通过在氧化铈纳米颗粒(CeO@ZIF-8)上原位生长ZIF-8纳米晶体构建了具有抗菌、抗氧化和成骨特性的核壳结构纳米杂化物。Ce/Ce比例可通过调节ZIF-8壳层厚度来控制。在合成过程中,壳层厚度随着与有机连接体配位的锌浓度升高而增加,导致CeO@ZIF-8中Ce/Ce比例增加,这进一步促进了其抗氧化酶模拟活性以及成骨特性。在体外,CeO@ZIF-8表现出优异的抗菌活性,在氧化应激状态下提供细胞保护作用,并促进成骨分化。在体内,CeO@ZIF-8可减轻细菌感染诱导的炎症反应并促进牙槽骨再生。通过生物信息学分析探索了其潜在机制,结果表明CeO@ZIF-8通过上调氧化还原酶活性促进铜锌超氧化物歧化酶(SOD1)的表达,从而减轻氧化应激并上调成骨相关基因和蛋白质的表达。上述研究结果表明,CeO@ZIF-8可同时实现抑菌、清除活性氧和成骨,从而完全满足牙周炎治疗的需求。