{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:48:57Z","timestamp":1792795737708,"version":"4.5.0"},"reference-count":66,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T00:00:00Z","timestamp":1750291200000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2025JJ60555"],"award-info":[{"award-number":["2025JJ60555"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp;amp; Translational Med"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Destruction of the blood\u2013spinal cord barrier (BSCB) following spinal cord injury (SCI) can result in various harmful cytokines, neutrophils, and macrophages infiltrating into the injured site, causing secondary damage. Growing evidence shows that M2 macrophages and their small extracellular vesicles (sEVs) contribute to tissue repair in various diseases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>In our previous proteomics\u2010based analysis of protein expression profiles in M2 macrophages and their sEVs (M2\u2010sEVs), the proteoglycan perlecan, encoded by HSPG2, was found to be upregulated in M2\u2010sEVs. Perlecan is a crucial component of basement membranes, playing a vital role in stabilising BSCB homeostasis and functions through its interactions with other matrix components, growth factors, and receptors. Here, we verified the high levels and remarkable therapeutic effect of M2\u2010sEV\u2010derived perlecan on the permeability of spinal cord microvascular endothelial cells exposed to oxygen glucose deprivation and reoxygenation in vitro. We also decorated the surface of M2\u2010sEVs with a fusion protein comprising the N\u2010terminus of Lamp2 and arginine glycine aspartic acid (RGD) peptides, which have an affinity for integrin \u03b1v\u03b23 and are primarily present on neovascular endothelium surfaces. In SCI model mice, these RGD\u2010M2\u2010sEVs accumulated at injured sites, promoting BSCB restoration. Finally, we identified M2\u2010sEV\u2010derived perlecan as a key player in regulating BSCB integrity and functional recovery post\u2010SCI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results indicate that RGD\u2010M2\u2010sEVs promote BSCB restoration by transporting perlecan to neovascular endothelial cells, representing a potential strategy for SCI treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Perlecan, a crucial component of basement membranes that plays a vital role in stabilising BSCB homeostasis and functions, was found to be upregulated in M2\u2010sEVs.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>M2\u2010sEVs decorated with RGD peptide can effectively target the neovascular endothelium surfaces at the injured spinal cord site.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>RGD\u2010M2\u2010sEVs promote BSCB restoration by transporting perlecan to neovascular endothelial cells, representing a potential strategy for SCI treatment.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.70381","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T05:58:52Z","timestamp":1750399132000},"source":"Crossref","is-referenced-by-count":7,"title":["Engineered small extracellular vesicles for targeted delivery of perlecan to stabilise the blood\u2013spinal cord barrier after spinal cord injury"],"prefix":"10.1002","volume":"15","author":[{"given":"Wei","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Spine Surgery Wuxi Ninth People's Hospital Affiliated to Soochow University  Wuxi China"},{"name":"Wuxi Orthopedic Institute  Wuxi China"},{"name":"Minimally Invasive Orthopedic Institute of Soochow University  Wuxi 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