State Key Laboratory of Tribology, Department of Mechanical Engineering, Tsinghua University, Beijing 100084, China.
Key Lab of Organic Optoelectronics and Molecular Engineering, Department of Chemistry, Tsinghua University, Beijing 100084, China.
ACS Appl Mater Interfaces. 2020 Nov 18;12(46):51236-51248. doi: 10.1021/acsami.0c14805. Epub 2020 Nov 9.
Osteoarthritis (OA) is a chronic joint disease and its progression and pathogenesis are highly associated with the significant increase of joint friction and overproduction of reactive oxygen species (ROS) in inflammation. Combination of ROS elimination and lubrication enhancement may provide a novel strategy for the treatment of OA. In the present study, a pure biomaterial and nondrug system P(DMA--MPC), synthesized via free radical copolymerization, was designed and developed for the first time using 2-methacryloxyethyl phosphorylcholine (MPC) as a bioinspired lubricant and -(3,4-dihydroxyphenethyl)methacrylamide (DMA) as an ROS scavenger. Our results showed that the P(DMA--MPC) aggregates could efficiently eliminate the ROS radicals and provide good lubrication property by adjusting the molar ratio of DMA and MPC in the copolymer. It is attributed to the antioxidant function of the hydroquinone moiety in DMA and the hydration lubrication effect of the zwitterionic phosphocholine group in MPC. Furthermore, the in vitro experiments demonstrated that the P(DMA--MPC) showed good biocompatibility with MC3T3-E1 cells and intracellular anti-inflammatory property by inhibiting the production of ROS and regulating the expression levels of pro-inflammatory cytokines, pain-related gene, anabolic genes, and catabolic genes. In conclusion, the drug-free P(DMA--MPC) aggregates developed herein can achieve dual functions of lubrication enhancement and anti-inflammatory effect and thus they may be representative as promising candidates for the treatment of OA.
骨关节炎(OA)是一种慢性关节疾病,其进展和发病机制与炎症中关节摩擦的显著增加和活性氧(ROS)的过度产生高度相关。消除 ROS 和增强润滑的联合作用可能为 OA 的治疗提供一种新策略。在本研究中,首次通过自由基共聚合成了一种纯生物材料和非药物系统 P(DMA-MPC),其中 2-(甲基丙烯酰氧基)乙基磷酸胆碱(MPC)用作仿生润滑剂,(3,4-二羟基苯乙基)甲基丙烯酰胺(DMA)用作 ROS 清除剂。我们的结果表明,通过调整共聚物中 DMA 和 MPC 的摩尔比,P(DMA-MPC) 聚集物可以有效地消除 ROS 自由基并提供良好的润滑性能。这归因于 DMA 中对苯二酚部分的抗氧化功能和 MPC 中两性离子磷酸胆碱基团的水合润滑作用。此外,体外实验表明,P(DMA-MPC) 通过抑制 ROS 的产生和调节促炎细胞因子、疼痛相关基因、合成代谢基因和分解代谢基因的表达水平,显示出良好的 MC3T3-E1 细胞生物相容性和抗炎作用。总之,本文开发的无药物 P(DMA-MPC) 聚集物可实现增强润滑和抗炎作用的双重功能,因此它们可能是治疗 OA 的有前途的候选药物。