State Key Laboratory of Tribology, Department of Mechanical Engineering, Tsinghua University, Beijing 100084, China.
Department of Biomaterials, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Provincial Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan 250012, China.
ACS Appl Mater Interfaces. 2022 Aug 10;14(31):35409-35422. doi: 10.1021/acsami.2c09120. Epub 2022 Jul 27.
The development of temporomandibular joint (TMJ) osteoarthritis is highly associated with mechanical overloading, which can result in accelerated cartilage degradation and damage due to increased interfacial friction and the release of inflammatory factors and catabolic enzymes. In the present study, we for the first time developed self-assembled drug-free nanospheres with pharmaceutical-active functions, which could be used as an intra-articularly injected biolubricant for the treatment of TMJ osteoarthritis based on a synergistic therapy of enhanced lubrication, anti-inflammation, and antisenescence. The nanospheres possessed the hydrophobic core of dopamine methacrylamide and the hydrophilic shell of sulfobetaine methacrylate, which formed into spherical aggregates in aqueous solution by specific interactions following reversible addition-fragmentation chain transfer polymerization. The biodegradation test, tribological test, and free radical scavenging test showed that the nanospheres were endowed with physiological stability, lubrication enhancement, and free radical scavenging capability. In addition, the in vitro cell test revealed that the nanospheres alleviated inflammatory and senescent phenotype for inflammation and oxidative stress stimulated chondrocytes. Furthermore, the in vivo animal test indicated that the nanospheres, after intra-articular injection into TMJ with an osteoarthritis environment, effectively protected condylar cartilage and subchondral bone from structural damage and attenuated cartilage matrix degradation and aging. In summary, the self-assembled nanospheres might be used as a promising biolubricant for achieving anti-inflammatory and antisenescent treatment of TMJ osteoarthritis.
颞下颌关节(TMJ)骨关节炎的发展与机械性过载高度相关,这可能导致由于界面摩擦力增加和炎症因子及分解代谢酶的释放而加速软骨降解和损伤。在本研究中,我们首次开发了具有药用活性功能的自组装无药物纳米球,可作为关节内注射用生物润滑剂,用于治疗 TMJ 骨关节炎,其基于增强润滑、抗炎和抗衰老的协同治疗。纳米球具有多巴胺甲基丙烯酰胺的疏水核和磺酸甜菜碱甲基丙烯酰胺的亲水壳,通过可逆加成-断裂链转移聚合后,通过特定相互作用在水溶液中形成球形聚集体。生物降解试验、摩擦学试验和自由基清除试验表明,纳米球具有生理稳定性、润滑增强和自由基清除能力。此外,体外细胞试验表明,纳米球缓解了炎症和氧化应激刺激的软骨细胞的炎症和衰老表型。此外,体内动物试验表明,纳米球在具有骨关节炎环境的 TMJ 关节内注射后,有效保护髁突软骨和软骨下骨免受结构损伤,并减轻软骨基质降解和老化。总之,自组装纳米球可用作一种有前途的生物润滑剂,用于实现 TMJ 骨关节炎的抗炎和抗衰老治疗。