{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T15:08:51Z","timestamp":1790262531994,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"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":["82370979"],"award-info":[{"award-number":["82370979"]}],"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":["82301108"],"award-info":[{"award-number":["82301108"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020737","name":"Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases","doi-asserted-by":"publisher","award":["14DZ2260300"],"award-info":[{"award-number":["14DZ2260300"]}],"id":[{"id":"10.13039\/100020737","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Small"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Mitochondrial transfer has emerged as a promising therapeutic strategy for disease driven by neural and pain\u2010related pathologies. However, inefficient intracellular delivery and severe lysosomal degradation significantly limit its translational potential. Given the critical role of mitochondrial dysfunction in Schwann cells (SCs) and macrophages during neuropathic pain progression in temporomandibular joint arthritis and knee osteoarthritis, this study presents an optimised nanomedicine treatment approach using mitochondria\u2010derived extracellular vesicles (MitoEVs). Here, we isolated functional MitoEVs from SCs for surface modification with a novel micellar material, R\n                    <jats:sub>8<\/jats:sub>\n                    \u2010HDA (yielding R\u2010MitoEVs), to enhance efficient endosomal escape. Our results demonstrate that R\u2010MitoEVs exhibit augmented cellular uptake and enhance evasion of lysosomal degradation, thereby preserving the structural integrity and bioactivity of the transferred mitochondria. Consequently, R\u2010MitoEVs suppressed lipopolysaccharide\u2010induced pro\u2010inflammatory macrophage polarisation and downregulated TNF\u2010\u03b1\/NF\u2010\u03baB signalling. Concurrently, the R\u2010MitoEV\u2010derived mitochondria restored metabolic homeostasis in SCs by quenching reactive oxygen species and augmenting antioxidant capacity. In vivo evaluations demonstrated the therapeutic efficacy of R\u2010MitoEVs, characterised by enhanced chondrocyte resilience and the significant downregulation of pain\u2010related neuronal markers (TRPV1 and CGRP) and pro\u2010inflammatory mediators. Overall, this surface\u2010engineered R\u2010MitoEVs platform mitigates the biological barriers of mitochondrial delivery, offering a promising therapeutic strategy for mitigating osteoarthritis and its associated neuropathic pain.\n                  <\/jats:p>","DOI":"10.1002\/smll.75883","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T14:41:40Z","timestamp":1790260900000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Surface\u2010Engineered Mitochondrial Extracellular Vesicles for Enhanced Endosomal Escape and Alleviation of Osteoarthritis\u2010Associated Neuropathic Pain"],"prefix":"10.1002","author":[{"given":"Zhan","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Oral Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine College of Stomatology National Center for Stomatology National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology Shanghai Research Institute of Stomatology Shanghai Jiao Tong University  Shanghai People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyu","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Oral Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine College of Stomatology National Center for Stomatology National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology Shanghai Research Institute of Stomatology Shanghai Jiao Tong University  Shanghai People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingwei","family":"Wu","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry Dental Materials Science Applied Oral Sciences &amp; Community Dental Care The University of Hong Kong  Hong Kong SAR People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Chao","sequence":"additional","affiliation":[{"name":"Department of Oral Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine College of Stomatology National Center for Stomatology National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology Shanghai Research Institute of Stomatology Shanghai Jiao Tong University  Shanghai People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianhao","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Oral Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine College of Stomatology National Center for Stomatology National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology Shanghai Research Institute of Stomatology Shanghai Jiao Tong University  Shanghai People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3010-1947","authenticated-orcid":false,"given":"Yangbin","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Orthopaedic Implants Department of Orthopaedic Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weifeng","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Oral Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine College of Stomatology National Center for Stomatology National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology Shanghai Research Institute of Stomatology Shanghai Jiao Tong University  Shanghai People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1276-1662","authenticated-orcid":false,"given":"Xuzhuo","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Oral Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine College of Stomatology National Center for Stomatology National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology Shanghai Research Institute of Stomatology Shanghai Jiao Tong University  Shanghai People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7879-3151","authenticated-orcid":false,"given":"Shanyong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oral Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine College of Stomatology National Center for Stomatology National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology Shanghai Research Institute of Stomatology Shanghai Jiao Tong University  Shanghai People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016\u2010022\u201008941\u20101"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2021.12.003"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572\u2010025\u201000594\u20106"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2024.122947"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23094642"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584\u2010025\u201001280\u20103"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.3c08046"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a041363"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.70623"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2014.77"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adt1318"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010025\u201009896\u2010x"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2025.01.031"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abe5085"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2021.11.020"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010024\u201007340\u20100"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12404"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2024.1453365"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931\u2010024\u201002739\u20109"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI84431"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2019.101148"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23169038"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.7b00221"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e35972"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.184379"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587\u2010023\u201001767\u2010y"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4314"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102105\u201012\u2010323"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059\u2010014\u20100550\u20108"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010018\u201028948\u2010z"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab447"}],"container-title":["Small"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/smll.75883","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/smll.75883","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/smll.75883","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T14:41:42Z","timestamp":1790260902000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/smll.75883"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,24]]},"references-count":31,"alternative-id":["10.1002\/smll.75883"],"URL":"https:\/\/doi.org\/10.1002\/smll.75883","archive":["Portico"],"relation":{},"ISSN":["1613-6810","1613-6829"],"issn-type":[{"value":"1613-6810","type":"print"},{"value":"1613-6829","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,24]]},"assertion":[{"value":"2026-04-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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