两性离子
微球
二甲双胍
骨关节炎
医学
材料科学
药理学
化学工程
纳米技术
化学
病理
内科学
胰岛素
分子
有机化学
替代医学
工程类
作者
Jiahui Hou,Ying-Yi Lin,Chencheng Zhu,Yupeng Chen,Rongmin Lin,Hancheng Lin,Jun Wang,Daogang Guan,Bin Yu,Jun Wang,Hangtian Wu,Zhuang Cui
标识
DOI:10.1002/advs.202402477
摘要
Chondrocyte senescence and reduced lubrication play pivotal roles in the pathogenesis of age-related osteoarthritis (OA). In the present study, highly lubricated and drug-loaded hydrogel microspheres are designed and fabricated through the radical polymerization of sulfobetaine (SB)-modified hyaluronic acid methacrylate using microfluidic technology. The copolymer contains a large number of SB and carboxyl groups that can provide a high degree of lubrication through hydration and form electrostatic loading interactions with metformin (Met@SBHA), producing a high drug load for anti-chondrocyte senescence. Mechanical, tribological, and drug release analyses demonstrated enhanced lubricative properties and prolonged drug dissemination of the Met@SBHA microspheres. RNA sequencing (RNA-seq) analysis, network pharmacology, and in vitro assays revealed the extraordinary capacity of Met@SBHA to combat chondrocyte senescence. Additionally, inducible nitric oxide synthase (iNOS) has been identified as a promising protein modulated by Met in senescent chondrocytes, thereby exerting a significant influence on the iNOS/ONOO-/P53 pathway. Notably, the intra-articular administration of Met@SBHA in aged mice ameliorated cartilage senescence and OA pathogenesis. Based on the findings of this study, Met@SBHA emerges as an innovative and promising strategy in tackling age-related OA serving the dual function of enhancing joint lubrication and mitigating cartilage senescence.
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