Wang Hui, Li Zuhao, Liu Jiaqi, Chang Haoran, Wang Jincheng, Song Shanliang, Zhao Yue, Zhao Xin
Department of Orthopaedics, The Second Hospital of Jilin University, Changchun 130041, China.
Department of Orthopaedics, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.
Int J Biol Macromol. 2024 Dec;282(Pt 2):136819. doi: 10.1016/j.ijbiomac.2024.136819. Epub 2024 Oct 22.
The progression of osteoarthritis (OA) is dramatically accelerated by excessive reactive oxygen species (ROS)-induced apoptosis of chondrocytes and the inflammatory response of synovial macrophages. In this study, we developed an injectable hydrogel with a catalase-mimicking nanozyme activity as a therapeutic agent for OA. In vitro experiments confirmed that the HA and peroxide-mimetic nanoenzyme-enhanced hydrogel, containing ε-polylysine/MnCoO (ε-PLE/MnCoO) nanoparticles, continuously eliminated ROS and inflammatory cytokines while promoting the polarization of inflammatory macrophages (M1 phenotype) towards anti-inflammatory macrophages (M2 phenotype) in dysfunctional microenvironments. When used for intraarticular injections in OA models, the nanoenzyme-enhanced hydrogel effectively reduced oxidative stress by scavenging ROS and regulating the immune microenvironment. It resulted in a subsequent reduction in the expression of inflammatory factors, including MMP-13, TNF-α, IL-1β, and iNOS in both the synovium and joint fluid. Moreover, cartilage repair was enhanced by the promotion of COL-2 and SOX-9 expression in the cartilage tissue, whereas osteophyte formation in OA was reduced. This study introduced an innovative treatment strategy for the clinical management of OA, demonstrating its significant potential for application in treating OA.
骨关节炎（OA）的进展因活性氧（ROS）过量诱导软骨细胞凋亡以及滑膜巨噬细胞的炎症反应而显著加速。在本研究中，我们开发了一种具有过氧化氢酶模拟纳米酶活性的可注射水凝胶作为OA的治疗剂。体外实验证实，含有ε-聚赖氨酸/锰钴氧化物（ε-PLE/MnCoO）纳米颗粒的透明质酸（HA）和过氧化物模拟纳米酶增强水凝胶在功能失调的微环境中持续清除ROS和炎性细胞因子，同时促进炎性巨噬细胞（M1表型）向抗炎巨噬细胞（M2表型）极化。当用于OA模型的关节内注射时，纳米酶增强水凝胶通过清除ROS和调节免疫微环境有效降低氧化应激。这导致滑膜和关节液中包括基质金属蛋白酶-13（MMP-13）、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和诱导型一氧化氮合酶（iNOS）在内的炎性因子表达随后减少。此外，通过促进软骨组织中Ⅱ型胶原蛋白（COL-2）和性别决定区Y盒9（SOX-9）的表达增强了软骨修复能力，而OA中的骨赘形成减少。本研究为OA的临床管理引入了一种创新的治疗策略，证明了其在治疗OA方面的巨大应用潜力。
