Injectable bioadhesive and lubricating hydrogel with polyphenol mediated single atom nanozyme for rheumatoid arthritis therapy

Huan He, Qin Zhang, Yiming Zhang, Shuxin Qu, Bin Li (), Jun Lin (), Xiong Lu () and Chaoming Xie ()
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Huan He: Southwest Jiaotong University
Qin Zhang: Medical Center of Soochow University
Yiming Zhang: Southwest Jiaotong University
Shuxin Qu: Southwest Jiaotong University
Bin Li: Soochow University
Jun Lin: Medical Center of Soochow University
Xiong Lu: Southwest Jiaotong University
Chaoming Xie: Southwest Jiaotong University

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract 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 (SO3−-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 SO3− 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.

Date: 2025
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DOI: 10.1038/s41467-025-58059-z

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