Inhibiting synovial inflammation and promoting cartilage repair in rheumatoid arthritis using a matrix metalloproteinase-binding hydrogel
Originating from synovial tissue, matrix metalloproteinase-9 (MMP-9) is a key inflammatory factor that promotes the formation and invasion of synovial pannus, leading to cartilage matrix destruction in rheumatoid arthritis (RA). However, clinical trials of systemic use of MMP-9 inhibitors are not su...
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Elsevier
2025-06-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006425003527 |
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| author | Zhanpeng Xue Nan Li Kaijun Du Jianxiong Shu Zhenwen Huang Zhifei Gao Xiaobo Xie Qi Li Yao Lu |
| author_facet | Zhanpeng Xue Nan Li Kaijun Du Jianxiong Shu Zhenwen Huang Zhifei Gao Xiaobo Xie Qi Li Yao Lu |
| author_sort | Zhanpeng Xue |
| collection | DOAJ |
| description | Originating from synovial tissue, matrix metalloproteinase-9 (MMP-9) is a key inflammatory factor that promotes the formation and invasion of synovial pannus, leading to cartilage matrix destruction in rheumatoid arthritis (RA). However, clinical trials of systemic use of MMP-9 inhibitors are not successful due to severe side effects. Thus, locally inhibiting MMP-9 may be an alternative in the treatment of RA. Herein, we developed MMP-9 binding peptide-functionalized copper sulfide nanoparticles (CuS-T NPs) and delivered them with light crosslinking chondroitin sulfate methacrylate (ChSMA) hydrogel. We found that the CuS NP-doped hydrogels could inhibit synovial inflammation. Specifically, the CuS-T/ChSMA hydrogel could rapidly bind to MMP-9, thereby inhibiting not only the invasion of RA fibroblast-like synoviocytes but also the polarization of inflammatory M1-type macrophages. The underlying mechanism involved the inhibition of the MAPK pathway. Moreover, ChSMA hydrogel provided a cartilage matrix-mimic microenvironment and synergistically promoted the generation of collagen-2 and aggrecan with CuS NPs. In an adjuvant-induced arthritis mouse model, the intra-articular injection of ChSMA/CuS-T hydrogel significantly alleviated synovial inflammation and accelerated cartilage repair without causing any side effects, killing two birds with one stone in RA therapy. |
| format | Article |
| id | doaj-art-94c9dc5d42f6450c9ce2262406972d02 |
| institution | Kabale University |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-94c9dc5d42f6450c9ce2262406972d022025-08-20T03:53:32ZengElsevierMaterials Today Bio2590-00642025-06-013210179210.1016/j.mtbio.2025.101792Inhibiting synovial inflammation and promoting cartilage repair in rheumatoid arthritis using a matrix metalloproteinase-binding hydrogelZhanpeng Xue0Nan Li1Kaijun Du2Jianxiong Shu3Zhenwen Huang4Zhifei Gao5Xiaobo Xie6Qi Li7Yao Lu8Department of Joint and Orthopedics, Orthopedic Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, ChinaDepartment of Joint and Orthopedics, Orthopedic Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, ChinaDepartment of Joint and Orthopedics, Orthopedic Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, ChinaDepartment of Joint and Orthopedics, Orthopedic Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, ChinaDepartment of Joint and Orthopedics, Orthopedic Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, ChinaThe Second School of Clinical Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, ChinaDepartment of Joint and Orthopedics, Orthopedic Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, China; Corresponding author.Department of Joint and Orthopedics, Orthopedic Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, China; Corresponding author.Department of Joint and Orthopedics, Orthopedic Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, China; The Second School of Clinical Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, China; State Key Laboratory of Multi-organ Injury Prevention and Treatment, Southern Medical University, Guangzhou, Guangdong, 510515, China; Corresponding author. Department of Joint and Orthopedics, Orthopedic Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, China.Originating from synovial tissue, matrix metalloproteinase-9 (MMP-9) is a key inflammatory factor that promotes the formation and invasion of synovial pannus, leading to cartilage matrix destruction in rheumatoid arthritis (RA). However, clinical trials of systemic use of MMP-9 inhibitors are not successful due to severe side effects. Thus, locally inhibiting MMP-9 may be an alternative in the treatment of RA. Herein, we developed MMP-9 binding peptide-functionalized copper sulfide nanoparticles (CuS-T NPs) and delivered them with light crosslinking chondroitin sulfate methacrylate (ChSMA) hydrogel. We found that the CuS NP-doped hydrogels could inhibit synovial inflammation. Specifically, the CuS-T/ChSMA hydrogel could rapidly bind to MMP-9, thereby inhibiting not only the invasion of RA fibroblast-like synoviocytes but also the polarization of inflammatory M1-type macrophages. The underlying mechanism involved the inhibition of the MAPK pathway. Moreover, ChSMA hydrogel provided a cartilage matrix-mimic microenvironment and synergistically promoted the generation of collagen-2 and aggrecan with CuS NPs. In an adjuvant-induced arthritis mouse model, the intra-articular injection of ChSMA/CuS-T hydrogel significantly alleviated synovial inflammation and accelerated cartilage repair without causing any side effects, killing two birds with one stone in RA therapy.http://www.sciencedirect.com/science/article/pii/S2590006425003527Rheumatoid arthritisMatrix metalloproteinase-9Chondroitin sulfate methacrylateCopper sulfide nanoparticles |
| spellingShingle | Zhanpeng Xue Nan Li Kaijun Du Jianxiong Shu Zhenwen Huang Zhifei Gao Xiaobo Xie Qi Li Yao Lu Inhibiting synovial inflammation and promoting cartilage repair in rheumatoid arthritis using a matrix metalloproteinase-binding hydrogel Materials Today Bio Rheumatoid arthritis Matrix metalloproteinase-9 Chondroitin sulfate methacrylate Copper sulfide nanoparticles |
| title | Inhibiting synovial inflammation and promoting cartilage repair in rheumatoid arthritis using a matrix metalloproteinase-binding hydrogel |
| title_full | Inhibiting synovial inflammation and promoting cartilage repair in rheumatoid arthritis using a matrix metalloproteinase-binding hydrogel |
| title_fullStr | Inhibiting synovial inflammation and promoting cartilage repair in rheumatoid arthritis using a matrix metalloproteinase-binding hydrogel |
| title_full_unstemmed | Inhibiting synovial inflammation and promoting cartilage repair in rheumatoid arthritis using a matrix metalloproteinase-binding hydrogel |
| title_short | Inhibiting synovial inflammation and promoting cartilage repair in rheumatoid arthritis using a matrix metalloproteinase-binding hydrogel |
| title_sort | inhibiting synovial inflammation and promoting cartilage repair in rheumatoid arthritis using a matrix metalloproteinase binding hydrogel |
| topic | Rheumatoid arthritis Matrix metalloproteinase-9 Chondroitin sulfate methacrylate Copper sulfide nanoparticles |
| url | http://www.sciencedirect.com/science/article/pii/S2590006425003527 |
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