He Huan, Zhang Qin, Zhang Yiming, Qu Shuxin, Li Bin, Lin Jun, Lu Xiong, Xie Chaoming
Institute of Biomedical Engineering, College of Medicine, Southwest Jiaotong University, Chengdu, 610031, Sichuan, China.
YiBin Research Institute, Southwest Jiaotong University, Chengdu, 610031, Sichuan, China.
Nat Commun. 2025 Mar 20;16(1):2768. doi: 10.1038/s41467-025-58059-z.
Rheumatoid arthritis (RA) is a common chronic autoimmune condition accompanied by lubrication dysfunction, inflammatory infiltration, and cartilage wear. Long-term improvements in joint lubrication, inflammation elimination, and worn cartilage repair are crucial for effective RA treatment. Herein, we present an injectable bioadhesive and lubricating hydrogel containing a dopamine-modified hyaluronic acid (DA-HA) network, sulfonated hyaluronic acid (SO-HA) network, and kartogenin (KGN)-grafted dopamine-hybridized graphene quantum dot-supported Cu single-atom nanozyme (DAGQD@Cu@KGN SAN) designed to restore cartilage lubrication and repair worn cartilage in RA. DA within the hydrogel networks provides bioadhesion, allowing it to persist in the joint cavity for extended periods. The hydrogel with SO group offer lubricity, reducing friction coefficient and alleviating cartilage wear. The DAGQD@Cu@KGN SAN exhibits excellent superoxide dismutase, catalase, and •OH scavenging activities, effectively inhibiting inflammation. KGN is sustainably released from the hydrogel, recruiting bone marrow mesenchymal stem cells to repair damaged cartilage by promoting their differentiation into chondrocytes. In vivo experimental results demonstrate that this injectable bioadhesive and lubricating hydrogel not only prevents cartilage wear and tear, providing long-term anti-oxidation and anti-inflammatory effects in early RA, but also repaired damaged cartilage in late-stage RA. This bio-adhesive and lubricating hydrogel presents a potential full-cycle strategy for RA therapy.
类风湿性关节炎（RA）是一种常见的慢性自身免疫性疾病，伴有润滑功能障碍、炎症浸润和软骨磨损。长期改善关节润滑、消除炎症以及修复磨损的软骨对于有效治疗RA至关重要。在此，我们展示了一种可注射的生物粘附性润滑水凝胶，其包含多巴胺修饰的透明质酸（DA-HA）网络、磺化透明质酸（SO-HA）网络以及角鲨素（KGN）接枝的多巴胺杂交石墨烯量子点负载的铜单原子纳米酶（DAGQD@Cu@KGN SAN），旨在恢复RA中的软骨润滑并修复磨损的软骨。水凝胶网络中的多巴胺提供生物粘附性，使其能够在关节腔内长期存留。含SO基团的水凝胶具有润滑性，可降低摩擦系数并减轻软骨磨损。DAGQD@Cu@KGN SAN表现出优异的超氧化物歧化酶、过氧化氢酶和•OH清除活性，能有效抑制炎症。KGN从水凝胶中持续释放，通过促进骨髓间充质干细胞分化为软骨细胞来修复受损软骨。体内实验结果表明，这种可注射的生物粘附性润滑水凝胶不仅能防止软骨磨损，在早期RA中提供长期的抗氧化和抗炎作用，还能修复晚期RA中受损的软骨。这种生物粘附性润滑水凝胶为RA治疗提供了一种潜在的全周期策略。
