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Addressing the underlying pathogenic mechanisms of IVD degeneration may inspire novel therapeutic strategy for LBP. Herein, hypoxic preconditioning improves both the biological function of MSCs in hostile microenvironments and enhances the production of small extracellular vesicles (sEVs) with desirable therapeutic functions. In vitro results reveal that hypoxic preconditional engineering sEVs (HP\u2010sEVs) alleviate the inflammatory microenvironments of IVD degradation, enhance the proliferation of nucleus pulposus (NP) cells, and promote proteoglycan synthesis and collagen formation. Transcriptomic sequencing reveales the excellent therapeutic effects of HP\u2010sEVs in promoting extracellular matrix regeneration through the delivery of microRNA(miR)\u20107\u20105p, which further suppresses p65 production and thus the inhibition of Cxcl2 production. Moreover, in vivo results further confirm the robust therapeutic role of HP\u2010sEVs in promoting IVD regeneration through the same mechanism mediated by miR\u20107\u20105p delivery. In conclusion, this study provides a novel therapeutic strategy for treating IVD degradation and is thus valuable for understanding the mechanism\u2010of\u2010action of HP\u2010sEVs in IVD regeneration associated with chronic lower back pain.<\/jats:p>","DOI":"10.1002\/advs.202304722","type":"journal-article","created":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T07:26:13Z","timestamp":1698045973000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Hypoxic Preconditional Engineering Small Extracellular Vesicles Promoted Intervertebral Disc Regeneration by Activating Mir\u20107\u20105p\/NF\u2010\u039ab\/Cxcl2 Axis"],"prefix":"10.1002","volume":"10","author":[{"given":"Hongxing","family":"Hu","sequence":"first","affiliation":[{"name":"Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration Ministry of Education Department of Orthopedics Tongji Hospital Affiliated to Tongji University School of 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