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Mater."],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Intervertebral disc degeneration pathogenesis involves chronic inflammation and cell death, highlighting the need for targeted therapeutic strategies. Extracellular vesicles (EVs) have emerged as promising bioactive materials for designing therapeutic approach. In this study, we demonstrate that youthful-state EVs (Y-EVs) outperform aged donor-derived EVs (O-EVs) in resolving inflammatory cascades within nucleus pulposus (NP) cells. EVs from young rats significantly suppressed TNF-\n                    <jats:italic>\u03b1<\/jats:italic>\n                    -induced inflammation in NP cells by reducing pro-inflammatory cytokine secretion, inhibiting extracellular matrix catabolism, and ameliorating rat disc degeneration\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Mechanistically, CD55 enrichment in Y-EVs attenuated NF-\n                    <jats:italic>\u03ba<\/jats:italic>\n                    B pathway activation, thereby disrupting inflammatory transcriptional programs. CD55 knockdown abrogated the anti-inflammatory efficacy of Y-EV, confirming its functional necessity. Besides, we identified thioredoxin (TRX) as a critical suppressor of NLRP1 inflammasome activation via direct protein binding, which inhibited NP cell pyroptosis. Crucially, CD55 in Y-EVs facilitated TRX-mediated NLRP1 suppression, whereas O-EVs failed to upregulate TRX or suppress the NLRP1 inflammasome. This study highlights the age-dependent functional divergence of EV bioactivity and establishes CD55 as a key determinant of their therapeutic superiority. The TRX\u2013NLRP1 interaction represents a novel target for disc degeneration intervention, positioning youthful-state EVs as an optimized bioactive material for disc regeneration strategies.\n                  <\/jats:p>","DOI":"10.1088\/1748-605x\/ae7ebc","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T05:42:00Z","timestamp":1783662120000},"page":"045008","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Youthful-state extracellular vesicles for targeted therapy of intervertebral disc degeneration: resolving inflammation and pyroptosis through NF-\n                    <i>\u03ba<\/i>\n                    B suppression and NLRP1 inactivation"],"prefix":"10.1088","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6723-2522","authenticated-orcid":false,"given":"Zhiwei","family":"Liao","sequence":"first","affiliation":[{"name":"Huazhong University of Science and Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Wang","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Lei","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3460-9735","authenticated-orcid":true,"given":"Bomansaan","family":"Herman","sequence":"additional","affiliation":[{"name":"North Henan Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Li","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0058-614X","authenticated-orcid":true,"given":"Cao","family":"Yang","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9960-7667","authenticated-orcid":true,"given":"Huipeng","family":"Yin","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology"},{"name":"Medical University of South Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"key":"bmmae7ebcbib1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2023.112119","type":"journal-article","article-title":"The mechanisms and functions of TNF-\u03b1 in intervertebral disc degeneration","volume":"174","author":"Pan","year":"2023","journal-title":"Exp. 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