{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T16:33:22Z","timestamp":1786638802767,"version":"build-2736575974"},"reference-count":60,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272499"],"award-info":[{"award-number":["82272499"]}],"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":["82571580"],"award-info":[{"award-number":["82571580"]}],"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"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Spinal cord injury (SCI) induces neuroinflammation predominantly mediated by microglia, thereby establishing a detrimental milieu that impedes neurological recovery. Extracellular vesicles (EVs) derived from umbilical cord mesenchymal stem cells (UCMSCs) possess considerable therapeutic potential; however, their clinical translation is constrained by insufficient bioactivity, poor targeting specificity, and uncontrolled release kinetics. Here, we present a multidimensional engineering strategy that overcomes these barriers synergistically. Tetramethylpyrazine (TMP)\u2010pretreated extracellular vesicles (TEVs) are enriched with anti\u2010inflammatory and pro\u2010regenerative factors in their cargo, while Angiopep\u20102 (Ang2) peptide\u2010modified TEVs (Ang\u2010TEVs) confer significantly enhanced microglial targeting. A reactive oxygen species (ROS)\u2010responsive hyaluronic acid (HA)\u2010phenylboronic acid (PBA)\/polyvinyl alcohol (PVA) hydrogel serves as an intelligent depot for sustained, on\u2010demand Ang\u2010TEVs release at the lesion site. This construct, Ang\u2010TEVs@Gel, demonstrated robust lesion accumulation and selective microglial uptake. It delivered miR\u2010664a\u20103p, which suppressed PIK3CA to attenuate PI3K\u2010AKT\u2010mTOR signaling and unleash autophagic flux, reprogramming microglia toward a reparative state that enhanced myelin debris clearance and quelled inflammation. Consequently, axonal regeneration and remyelination were markedly improved, driving significant motor recovery in SCI mice. By integrating preconditioning, active targeting, and stimuli\u2010responsive biomaterials, this strategy provides an elegant blueprint for engineering EV\u2010based therapies to repair the injured central nervous system.<\/jats:p>","DOI":"10.1002\/advs.77117","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T15:45:36Z","timestamp":1786635936000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Multidimensional Engineering Strategy Reprograms Microglia via Targeted and Sustained\u2010Release Extracellular Vesicles for Spinal Cord Injury Repair"],"prefix":"10.1002","author":[{"given":"Wu","family":"Xiong","sequence":"first","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minhao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingming","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of human anatomy School of Basic Medicine Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jizhou","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of human anatomy School of Basic Medicine Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of human anatomy School of Basic Medicine Nanjing Medical University  Nanjing Jiangsu 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Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of human anatomy School of Basic Medicine Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiran","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of human anatomy School of Basic Medicine Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of Nanjing Medical University  Nanjing Jiangsu 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Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8293-2028","authenticated-orcid":false,"given":"Jin","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.biomaterials.2021.121279","article-title":"A DAMP\u2010Scavenging, IL\u201010\u2010Releasing Hydrogel Promotes Neural Regeneration and Motor Function Recovery After Spinal Cord Injury","volume":"280","author":"Shen H.","year":"2022","journal-title":"Biomaterials"},{"issue":"12","key":"e_1_2_12_3_1","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1038\/s41593-022-01196-1","article-title":"Natural and Targeted 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