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The inflammatory microenvironment promotes ECM degradation, further exacerbating the vicious cycle of nucleus pulposus (NP) degeneration. This study introduces the mRNA encoding a novel therapeutic transcription factor, Brachyury (Bry), into nucleus pulposus cells (NPCs) using an injectable microsphere system composed of biomimetic GelMA\/Fucoidan (FU) dual\u2010component hydrogel (GF) and surface chemically grafted lipid nanoparticles (LNP) (BLNP@GF). The study aims to alleviate inflammatory response in the NP while restoring the ECM secretion function of NPCs and enhancing the ability of NPCs to withstand inflammatory stress, thereby restoring physiological balance in the NP microenvironment. The GF microspheres demonstrate injectability and porosity, facilitating efficient LNP loading through chemical grafting. In the LPS\u2010simulated inflammatory microenvironment, sustained release of FU significantly reduces inflammatory activity in NPCs. Successful transfection with Bry mRNA upregulate ECM synthesis in degenerated NPCs. In a rat tail puncture IVDD model, local application of BLNP@GF microspheres effectively improved ECM remodeling in NP tissue, thereby ameliorating puncture\u2010induced IVDD. In conclusion, FU\u2010functionalized GelMA hydrogel microspheres loaded with Bry mRNA provide a promising new strategy for reversing IVDD.<\/jats:p>","DOI":"10.1002\/advs.202504195","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T07:49:32Z","timestamp":1750405772000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Brachyury\u2010Activated Fucoidan Hydrogel Microspheres Rejuvenate Degenerative Intervertebral Discs Microenvironment"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0063-3545","authenticated-orcid":false,"given":"Yuhao","family":"Gong","sequence":"first","affiliation":[{"name":"Department of Orthopedics the Affiliated Suzhou Hospital of Nanjing Medical University Suzhou Municipal Hospital Gusu School Nanjing Medical University  Suzhou 215006 P. R. 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