Controlled TPCA-1 delivery engineers a pro-tenogenic niche to initiate tendon regeneration by targeting IKKβ/NF-κB signaling
Tendon repair remains challenging due to its poor intrinsic healing capacity, and stem cell therapy has emerged as a promising strategy to promote tendon regeneration. Nevertheless, the inflammatory environment following acute tendon injuries disrupts stem cell differentiation, leading to unsatisfie...
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KeAi Communications Co., Ltd.
2025-02-01
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| Series: | Bioactive Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X24004614 |
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| author | Jialin Chen Renwang Sheng Qingyun Mo Ludvig J. Backman Zhiyuan Lu Qiuzi Long Zhixuan Chen Zhicheng Cao Yanan Zhang Chuanquan Liu Haotian Zheng Yu Qi Mumin Cao Yunfeng Rui Wei Zhang |
| author_facet | Jialin Chen Renwang Sheng Qingyun Mo Ludvig J. Backman Zhiyuan Lu Qiuzi Long Zhixuan Chen Zhicheng Cao Yanan Zhang Chuanquan Liu Haotian Zheng Yu Qi Mumin Cao Yunfeng Rui Wei Zhang |
| author_sort | Jialin Chen |
| collection | DOAJ |
| description | Tendon repair remains challenging due to its poor intrinsic healing capacity, and stem cell therapy has emerged as a promising strategy to promote tendon regeneration. Nevertheless, the inflammatory environment following acute tendon injuries disrupts stem cell differentiation, leading to unsatisfied outcomes. Our study recognized the critical role of NF-κB signaling in activating inflammation and suppressing tenogenic differentiation of stem cells after acute tendon injury via multiomics analysis. TPCA-1, a selective inhibitor of IKKβ/NF-κB signaling, efficiently restored the impaired tenogenesis of stem cells in the inflammatory environment. By developing a microsphere-incorporated hydrogel system for stem cell delivery and controlled release of TPCA-1, we successfully engineered a pro-tenogenic niche to initiate tenogenesis for tendon regeneration. Collectively, we recognize NF-κB signaling as a critical target to tailor a pro-tenogenic niche and propose the combined delivery of stem cells and TPCA-1 as a potential strategy for acute tendon injuries. |
| format | Article |
| id | doaj-art-d6601ff863ad48069e4c155fd20cd778 |
| institution | DOAJ |
| issn | 2452-199X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj-art-d6601ff863ad48069e4c155fd20cd7782025-08-20T02:39:29ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-02-014431933810.1016/j.bioactmat.2024.10.016Controlled TPCA-1 delivery engineers a pro-tenogenic niche to initiate tendon regeneration by targeting IKKβ/NF-κB signalingJialin Chen0Renwang Sheng1Qingyun Mo2Ludvig J. Backman3Zhiyuan Lu4Qiuzi Long5Zhixuan Chen6Zhicheng Cao7Yanan Zhang8Chuanquan Liu9Haotian Zheng10Yu Qi11Mumin Cao12Yunfeng Rui13Wei Zhang14School of Medicine, Southeast University, 210009, Nanjing, China; Center for Stem Cell and Regenerative Medicine, Southeast University, 210009, Nanjing, China; Department of Ophthalmology, Zhongda Hospital, Southeast University, 210009, Nanjing, China; Jiangsu Key Laboratory for Biomaterials and Devices, Southeast University, 210096, Nanjing, China; China Orthopedic Regenerative Medicine Group (CORMed), 310058, Hangzhou, China; Corresponding author. School of Medicine, Southeast University, 210009, Nanjing, China.School of Medicine, Southeast University, 210009, Nanjing, China; Department of Orthopaedics, Zhongda Hospital, Southeast University, 210009, Nanjing, China; Center for Stem Cell and Regenerative Medicine, Southeast University, 210009, Nanjing, ChinaSchool of Medicine, Southeast University, 210009, Nanjing, China; Center for Stem Cell and Regenerative Medicine, Southeast University, 210009, Nanjing, ChinaDepartment of Medical and Translational Biology, Anatomy, Umeå University, 90187, Umeå, Sweden; Department of Community Medicine and Rehabilitation, Section of Physiotherapy, Umeå University, 90187, Umeå, SwedenSchool of Medicine, Southeast University, 210009, Nanjing, China; Center for Stem Cell and Regenerative Medicine, Southeast University, 210009, Nanjing, ChinaCenter for Stem Cell and Regenerative Medicine, Southeast University, 210009, Nanjing, ChinaSchool of Medicine, Southeast University, 210009, Nanjing, China; Center for Stem Cell and Regenerative Medicine, Southeast University, 210009, Nanjing, ChinaDepartment of Orthopaedic Surgery, Institute of Digital Medicine, Nanjing First Hospital, Nanjing Medical University, 210006, Nanjing, ChinaSchool of Medicine, Southeast University, 210009, Nanjing, China; Center for Stem Cell and Regenerative Medicine, Southeast University, 210009, Nanjing, ChinaSchool of Medicine, Southeast University, 210009, Nanjing, China; Center for Stem Cell and Regenerative Medicine, Southeast University, 210009, Nanjing, ChinaSchool of Medicine, Southeast University, 210009, Nanjing, China; Center for Stem Cell and Regenerative Medicine, Southeast University, 210009, Nanjing, ChinaSchool of Medicine, Southeast University, 210009, Nanjing, China; Center for Stem Cell and Regenerative Medicine, Southeast University, 210009, Nanjing, ChinaSchool of Medicine, Southeast University, 210009, Nanjing, China; Department of Orthopaedics, Zhongda Hospital, Southeast University, 210009, Nanjing, ChinaSchool of Medicine, Southeast University, 210009, Nanjing, China; Department of Orthopaedics, Zhongda Hospital, Southeast University, 210009, Nanjing, China; Corresponding author. School of Medicine, Southeast University, 210009, Nanjing, China.School of Medicine, Southeast University, 210009, Nanjing, China; Center for Stem Cell and Regenerative Medicine, Southeast University, 210009, Nanjing, China; Jiangsu Key Laboratory for Biomaterials and Devices, Southeast University, 210096, Nanjing, China; China Orthopedic Regenerative Medicine Group (CORMed), 310058, Hangzhou, China; Corresponding author. School of Medicine, Southeast University, 210009, Nanjing, China.Tendon repair remains challenging due to its poor intrinsic healing capacity, and stem cell therapy has emerged as a promising strategy to promote tendon regeneration. Nevertheless, the inflammatory environment following acute tendon injuries disrupts stem cell differentiation, leading to unsatisfied outcomes. Our study recognized the critical role of NF-κB signaling in activating inflammation and suppressing tenogenic differentiation of stem cells after acute tendon injury via multiomics analysis. TPCA-1, a selective inhibitor of IKKβ/NF-κB signaling, efficiently restored the impaired tenogenesis of stem cells in the inflammatory environment. By developing a microsphere-incorporated hydrogel system for stem cell delivery and controlled release of TPCA-1, we successfully engineered a pro-tenogenic niche to initiate tenogenesis for tendon regeneration. Collectively, we recognize NF-κB signaling as a critical target to tailor a pro-tenogenic niche and propose the combined delivery of stem cells and TPCA-1 as a potential strategy for acute tendon injuries.http://www.sciencedirect.com/science/article/pii/S2452199X24004614Acute tendon injuryStem cell therapyNF-κB signalingTenogenic differentiationMultiomics |
| spellingShingle | Jialin Chen Renwang Sheng Qingyun Mo Ludvig J. Backman Zhiyuan Lu Qiuzi Long Zhixuan Chen Zhicheng Cao Yanan Zhang Chuanquan Liu Haotian Zheng Yu Qi Mumin Cao Yunfeng Rui Wei Zhang Controlled TPCA-1 delivery engineers a pro-tenogenic niche to initiate tendon regeneration by targeting IKKβ/NF-κB signaling Bioactive Materials Acute tendon injury Stem cell therapy NF-κB signaling Tenogenic differentiation Multiomics |
| title | Controlled TPCA-1 delivery engineers a pro-tenogenic niche to initiate tendon regeneration by targeting IKKβ/NF-κB signaling |
| title_full | Controlled TPCA-1 delivery engineers a pro-tenogenic niche to initiate tendon regeneration by targeting IKKβ/NF-κB signaling |
| title_fullStr | Controlled TPCA-1 delivery engineers a pro-tenogenic niche to initiate tendon regeneration by targeting IKKβ/NF-κB signaling |
| title_full_unstemmed | Controlled TPCA-1 delivery engineers a pro-tenogenic niche to initiate tendon regeneration by targeting IKKβ/NF-κB signaling |
| title_short | Controlled TPCA-1 delivery engineers a pro-tenogenic niche to initiate tendon regeneration by targeting IKKβ/NF-κB signaling |
| title_sort | controlled tpca 1 delivery engineers a pro tenogenic niche to initiate tendon regeneration by targeting ikkβ nf κb signaling |
| topic | Acute tendon injury Stem cell therapy NF-κB signaling Tenogenic differentiation Multiomics |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X24004614 |
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