Rapamycin incorporating hydrogel improves the progression of osteoarthritis by inducing synovial macrophages polarization and reducing intra-articular inflammation
In the macrophage-specific mTORC1 signaling activation model, the synovial macrophages polarized toward M1, thus aggravating synovitis and progression of OA. Therefore, intra-articular injection of rapamycin, a classical mTORC1 inhibitor, may show great potential for alleviating synovitis and delayi...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Materials & Design |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0264127522011650 |
| _version_ | 1811175494126665728 |
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| author | Bo Chen Jibing Wang Xing Jin Xin Wang Zhangling Fan Yuxin Zhang Xuehan Sang Zhaoxiang Meng |
| author_facet | Bo Chen Jibing Wang Xing Jin Xin Wang Zhangling Fan Yuxin Zhang Xuehan Sang Zhaoxiang Meng |
| author_sort | Bo Chen |
| collection | DOAJ |
| description | In the macrophage-specific mTORC1 signaling activation model, the synovial macrophages polarized toward M1, thus aggravating synovitis and progression of OA. Therefore, intra-articular injection of rapamycin, a classical mTORC1 inhibitor, may show great potential for alleviating synovitis and delaying cartilage destruction in osteoarthritis (OA). However, the durable retention of drugs in the joint cavity is still a critical issue to be addressed. Herein, we crosslinked the Poloxamer 407 and hyaluronic acid (P-HA) to prepare an injectable and thermo-responsive drug delivery system to durably retain rapamycin and dramatically magnify their therapeutic effects in OA management. The prepared P-HA hydrogel showed excellent biocompatibility with chondrocytes and fibroblasts, as well as possessed sustained rapamycin release profiles for 14 days. Intra-articular injection of this rapamycin-incorporated P-HA hydrogel indicated a positively effect on inducing the polarization of synovial macrophages from M1 to M2 phenotype and reducing synovial inflammation in OA. This strategy significantly decreased the pro-inflammatory cytokines (e.g., TNF-α, IL-1β, and IL-6) and increased the anti-inflammatory cytokine (e.g., IL-10) expression in the synovial tissues and synovial fluid. As a result, intra-articular injection of rapamycin-incorporated P-HA hydrogel significantly prevented cartilage destruction by inducing cartilage matrix formation, which suggesting a great potential for the management of OA. |
| first_indexed | 2024-04-10T19:36:52Z |
| format | Article |
| id | doaj.art-b47ad0f104b64643a8891dd39a7c5fb4 |
| institution | Directory Open Access Journal |
| issn | 0264-1275 |
| language | English |
| last_indexed | 2024-04-10T19:36:52Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials & Design |
| spelling | doaj.art-b47ad0f104b64643a8891dd39a7c5fb42023-01-30T04:12:30ZengElsevierMaterials & Design0264-12752023-01-01225111542Rapamycin incorporating hydrogel improves the progression of osteoarthritis by inducing synovial macrophages polarization and reducing intra-articular inflammationBo Chen0Jibing Wang1Xing Jin2Xin Wang3Zhangling Fan4Yuxin Zhang5Xuehan Sang6Zhaoxiang Meng7Rehabilitation Medicine Department, Northern Jiangsu People’s Hospital, Yangzhou, Jiangsu 225001, ChinaRehabilitation Medicine Department, Northern Jiangsu People’s Hospital, Yangzhou, Jiangsu 225001, ChinaRehabilitation Medicine Department, Northern Jiangsu People’s Hospital, Yangzhou, Jiangsu 225001, ChinaRehabilitation Medicine Department, Northern Jiangsu People’s Hospital, Yangzhou, Jiangsu 225001, ChinaRehabilitation Medicine Department, Northern Jiangsu People’s Hospital, Yangzhou, Jiangsu 225001, ChinaDepartment of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai 200011, ChinaRehabilitation Medicine Department, Northern Jiangsu People’s Hospital, Yangzhou, Jiangsu 225001, ChinaRehabilitation Medicine Department, Northern Jiangsu People’s Hospital, Yangzhou, Jiangsu 225001, China; Corresponding author.In the macrophage-specific mTORC1 signaling activation model, the synovial macrophages polarized toward M1, thus aggravating synovitis and progression of OA. Therefore, intra-articular injection of rapamycin, a classical mTORC1 inhibitor, may show great potential for alleviating synovitis and delaying cartilage destruction in osteoarthritis (OA). However, the durable retention of drugs in the joint cavity is still a critical issue to be addressed. Herein, we crosslinked the Poloxamer 407 and hyaluronic acid (P-HA) to prepare an injectable and thermo-responsive drug delivery system to durably retain rapamycin and dramatically magnify their therapeutic effects in OA management. The prepared P-HA hydrogel showed excellent biocompatibility with chondrocytes and fibroblasts, as well as possessed sustained rapamycin release profiles for 14 days. Intra-articular injection of this rapamycin-incorporated P-HA hydrogel indicated a positively effect on inducing the polarization of synovial macrophages from M1 to M2 phenotype and reducing synovial inflammation in OA. This strategy significantly decreased the pro-inflammatory cytokines (e.g., TNF-α, IL-1β, and IL-6) and increased the anti-inflammatory cytokine (e.g., IL-10) expression in the synovial tissues and synovial fluid. As a result, intra-articular injection of rapamycin-incorporated P-HA hydrogel significantly prevented cartilage destruction by inducing cartilage matrix formation, which suggesting a great potential for the management of OA.http://www.sciencedirect.com/science/article/pii/S0264127522011650Intra-articular injectionHydrogelRapamycinSynovial macrophagesOsteoarthritis |
| spellingShingle | Bo Chen Jibing Wang Xing Jin Xin Wang Zhangling Fan Yuxin Zhang Xuehan Sang Zhaoxiang Meng Rapamycin incorporating hydrogel improves the progression of osteoarthritis by inducing synovial macrophages polarization and reducing intra-articular inflammation Materials & Design Intra-articular injection Hydrogel Rapamycin Synovial macrophages Osteoarthritis |
| title | Rapamycin incorporating hydrogel improves the progression of osteoarthritis by inducing synovial macrophages polarization and reducing intra-articular inflammation |
| title_full | Rapamycin incorporating hydrogel improves the progression of osteoarthritis by inducing synovial macrophages polarization and reducing intra-articular inflammation |
| title_fullStr | Rapamycin incorporating hydrogel improves the progression of osteoarthritis by inducing synovial macrophages polarization and reducing intra-articular inflammation |
| title_full_unstemmed | Rapamycin incorporating hydrogel improves the progression of osteoarthritis by inducing synovial macrophages polarization and reducing intra-articular inflammation |
| title_short | Rapamycin incorporating hydrogel improves the progression of osteoarthritis by inducing synovial macrophages polarization and reducing intra-articular inflammation |
| title_sort | rapamycin incorporating hydrogel improves the progression of osteoarthritis by inducing synovial macrophages polarization and reducing intra articular inflammation |
| topic | Intra-articular injection Hydrogel Rapamycin Synovial macrophages Osteoarthritis |
| url | http://www.sciencedirect.com/science/article/pii/S0264127522011650 |
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