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The early stage of IVDD is marked by excessive oxidative stress, lipid peroxidation, iron dysregulation and sustained catabolic enzyme activity, while late\u2010stage cellular aging ultimately renders NP cells highly susceptible to iron\u2010dependent cell death. To address these stage\u2010specific challenges, we developed a pathology\u2010adaptive self\u2010assembling hydrogel that exploits dynamically varying catabolic enzyme activity to trigger on\u2010demand delivery of antioxidant molecules and bioactive extracellular vesicles. Upon recognition of pathologically elevated MMP13, the hydrogel undergoes site\u2010specific structural disruption, thereby enabling spatiotemporally controlled exosome release. The hydrogel complex stabilizes redox balance by boosting intracellular glutathione, mitigating lipid peroxidation and restoring iron homeostasis. Furthermore, it activates PI3K\u2010Akt signaling and reinstates key anti\u2010ferroptosis proteins. Simultaneously, it promotes the synthesis of proteoglycans and type II collagen, collectively rebuilding the ECM niche. The combined effect of restored redox balance and regenerative signaling leads to significant structural and functional recovery of the damaged disc, as strongly evidenced in vivo animal studies. Overall, this spatiotemporal\u2010adaptive platform establishes a multifaceted strategy for regenerative engineering, offering a promising option for complex degenerative diseases.<\/jats:p>","DOI":"10.1002\/adma.74189","type":"journal-article","created":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T21:44:11Z","timestamp":1785015851000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pathology\u2010Responsive Self\u2010Assembling Hydrogel Enabling Spatiotemporally Controlled Exosome Release and Redox Regulation for Intervertebral Disc Regeneration"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-8812-0538","authenticated-orcid":false,"given":"Zhan","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Orthopaedics The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University Wenzhou Zhejiang Province China"},{"name":"The 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