Affiliations: [a] Department of Orthopedics, Hangzhou Fuyang Hospital of TCM Orthopedics and Traumatology, Hangzhou, China | [b] Department of Medical Research, Zhejiang Zhongwei Medical Research Co., Ltd, Hangzhou, China | [c] School of Materials Science and Engineering, Zhejiang Sci-Tech University, Hangzhou, China
Correspondence:
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Corresponding authors: Guohua Jiang, School of Materials Science and Engineering, Zhejiang Sci-Tech University, Hangzhou, Zhejiang, 310000, China. E-mail: ghjiang_cn@zstu.edu.cn and Xiaodan He, Department of Orthopedics, Hangzhou Fuyang Hospital of TCM Orthopedics and Traumatology, Hangzhou, Zhejiang, 310000, China. E-mail: hxd3380@163.com
Note: [†] These authors contributed equally to this work.
Abstract: BACKGROUND:Osteoarthritis (OA) is a chronic and degenerative joint disease that remains a great challenge in treatment due to the lack of effective therapies. 4-octyl itaconate (4-OI) is a novel and potent modulator of inflammation for the treatment of inflammatory disease. However, the clinical usage of 4-OI is limited due to its poor solubility and low bioavailability. As a promising drug delivery strategy, injectable hydrogels offers an effective approach to address these limitations of 4-OI. OBJECTIVE:The aim of the study was to verify that the composite 4-OI/SA hydrogels could achieve a controlled release of 4-OI and reduce damage to articular cartilage in the group of osteoarthritic rats treated with the system. METHODS:In this study, an injectable composite hydrogel containing sodium alginate (SA) and 4-octyl itaconate (4-OI) has been developed for continuous intra-articular administration in the treatment of OA. RESULTS:After intra-articular injection in arthritic rats, the as-prepared 4-OI/SA hydrogel containing of 62.5 μM 4-OI effectively significantly reduced the expression of TNF-α, IL-1β, IL-6 and MMP3 in the ankle fluid. Most importantly, the as-prepared 4-OI/SA hydrogel system restored the morphological parameters of the ankle joints close to normal. CONCLUSION:4-OI/SA hydrogel shows a good anti-inflammatory activity and reverse cartilage disruption, which provide a new strategy for the clinical treatment of OA.
