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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Main Authors: 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
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2025-02-01
Series:Bioactive Materials
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Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X24004614
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Summary: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.
ISSN:2452-199X