{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:42:05Z","timestamp":1792172525064,"version":"4.4.0"},"reference-count":56,"publisher":"Wiley","issue":"30","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai Municipality","doi-asserted-by":"publisher","award":["25ZR1402422"],"award-info":[{"award-number":["25ZR1402422"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai Municipality","doi-asserted-by":"publisher","award":["24ZR1476100"],"award-info":[{"award-number":["24ZR1476100"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82372441"],"award-info":[{"award-number":["82372441"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82572737"],"award-info":[{"award-number":["82572737"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32401094"],"award-info":[{"award-number":["32401094"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Chronic inflammation\u2010driven bone loss in aging compromises bone regeneration and further impairs the bone\u2010tendon interface (BTI). However, the cellular mechanisms by which inflammation exacerbates cellular senescence and consequently disrupts BTI healing remain unclear. Here, we identify M1 macrophage\u2010mediated inflammation as a key driver of bone marrow\u2010derived mesenchymal stem cells (BMSCs) senescence and bone microstructural deterioration. This senescence\u2010associated decline in BMSCs ultimately compromises osteogenesis and delays BTI repair. To counteract these effects, we engineered a senomorphic and immunomodulatory platform by incorporating quercetin\u2010primed senomorphic small extracellular vesicles (Sm\u2010sEV) into a tissue\u2010adhesive \u03b1\u2010lipoic acid hydrogel (\u03b1LA\u2010Gel) for sustained local delivery. The composite material modulates the inflammatory\u2010senescent microenvironment by attenuating M1 macrophage\u2010driven inflammation and enhancing BMSC resilience to inflammation\u2010exacerbated senescence. Mechanistic analyses revealed that Sm\u2010sEV\/\u03b1LA\u2010Gel suppresses cGAS\u2010STING\u2010NF\u2010\u03baB signaling, thereby reducing inflammation and improving BMSC resistance to senescence. In an osteoporotic rat rotator cuff repair model, Sm\u2010sEV\/\u03b1LA\u2010Gel enhanced bone formation and fibrocartilage maturation, thereby promoting superior BTI integration and mechanical strength. Together, these findings identify inflammation\u2010exacerbated BMSC senescence as a key pathological driver and demonstrate that dual regulation of inflammation and stem cell resilience enables robust regeneration of bone and the BTI under osteoporotic conditions.<\/jats:p>","DOI":"10.1002\/advs.202524366","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T19:46:19Z","timestamp":1775591179000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Senomorphic Small Extracellular Vesicles Delivered by a Tissue\u2010Adhesive \u03b1\u2010Lipoic\u2010Acid Hydrogel Enable Immuno\u2010Rejuvenation for Bone\u2010Tendon Interface Regeneration"],"prefix":"10.1002","volume":"13","author":[{"given":"Lingzhi","family":"Kong","sequence":"first","affiliation":[{"name":"Department of Sports Medicine Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wencai","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhao","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Li","sequence":"additional","affiliation":[{"name":"Biomedical Engineering Department, School of Engineering STEM College, RMIT University Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanlun","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of High Performance Ceramics Shanghai Institute of Ceramics Chinese Academy of Sciences  Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8260-7161","authenticated-orcid":false,"given":"Yaohua","family":"He","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai P. R. China"},{"name":"Department of Orthopedic Surgery Jinshan District Central Hospital affiliated to Shanghai University of Medicine &amp; Health Sciences Jinshan Branch of Shanghai Sixth People's Hospital  Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.25211"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1810692116"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-024-00492-3"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2025.6003"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413\u2010025\u201000450\u2010z"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmat4863"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/adbi.202300331"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2025.147928"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S423819"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/nsr\/nwae076"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.5c15449"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13062\u2010023\u201000394\u20106"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010022\u201005535\u2010x"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.5c05416"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12154"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951\u2010024\u201002509\u20101"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202408255"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adp7872"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/EXP.20240349"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3402\/jev.v4.26238"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2025.123562"},{"key":"e_1_2_9_23_1","article-title":"Artificial Mucus Layer Formed in Response to ROS for the Oral Treatment of Inflammatory Bowel Disease","volume":"10","author":"Zhang G.","year":"2024","journal-title":"Z He, Q Fu, Sci Adv"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201061070\u2010z"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.crbiot.2023.100120"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1251152"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s41232\u2010023\u201000279\u20101"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413\u2010024\u201000346\u20104"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.3c03793"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1155\/ijog\/6175946"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287\u2010021\u201002453\u2010z"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4324"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201010677\u20100"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2024.11.005"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010023\u201001502\u20108"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202207097"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413\u2010024\u201000375\u2010z"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13770\u2010024\u201000663\u2010z"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13018\u2010025\u201005785\u20101"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2022.07.022"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adl0372"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1080\/10409238.2019.1610722"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aav4319"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/jbmr\/zjaf029"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2025.02.771"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2025.114477"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010023\u201006373\u20101"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010020\u201003341\u20109"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011\u2010024\u201001860\u20101"},{"key":"e_1_2_9_50_1","first-page":"85","article-title":"Biological Approaches to the Repair and Regeneration of the Rotator Cuff Tendon\u2010bone Enthesis: A Literature Review","volume":"4","author":"Abdalla A. A.","year":"2023","journal-title":"Biomater Transl"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202304090"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2022.07.003"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arthro.2024.09.021"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.5c01332"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9101011"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951\u2010024\u201002603\u20104"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1177\/03635465231171682"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202524366","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202524366","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202524366","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T14:24:59Z","timestamp":1781533499000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202524366"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,7]]},"references-count":56,"journal-issue":{"issue":"30","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1002\/advs.202524366"],"URL":"https:\/\/doi.org\/10.1002\/advs.202524366","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,7]]},"assertion":[{"value":"2025-12-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e24366"}}