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Treg\u2010derived exosomes (TExo) exhibit low immunogenicity while enriching regenerative signaling relative to parental Tregs. Current exosome carriers place greater emphasis on sustained release than on factors affecting vesicle stability, such as nonspecific interactions and confinement effects. Inspired by the multivesicular body (MVB), we engineered artificial Tregs (ATregs) with an MVB\u2010like architecture that integrates vesicle protection with sustained release through a reconstructed storage microenvironment. This design enables phase\u2010aligned TExo release and extends functional activity by more than an order of magnitude compared with free TExo. ATregs sequentially coordinate the suppression of inflammation, enhancement of angiogenesis, and stimulation of skin appendage regeneration. In diabetic wounds and deep second\u2010degree burn models, which represent intrinsic repair dysfunction and severe structural tissue loss, ATregs markedly accelerate healing and outperform conventional strategies across murine and porcine models. These findings overcome the key limitations of exosome therapies and open a new avenue for next\u2010generation regenerative therapeutics.<\/jats:p>","DOI":"10.1002\/adma.75362","type":"journal-article","created":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T07:38:17Z","timestamp":1791617897000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Artificial Regulatory T Cells Orchestrate Phase\u2010Spanning Regeneration in Refractory Tissue Injuries"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1125-8241","authenticated-orcid":false,"given":"Bo","family":"Li","sequence":"first","affiliation":[{"name":"Department of Sports Medicine Center for Orthopedic Surgery Orthopedic Hospital of Guangdong Province The Third School of Clinical Medicine Southern Medical University The Third Affiliated Hospital of Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiale","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine The Second Affiliated Hospital of Chongqing Medical University  Chongqing China"},{"name":"BRICS Joint Laboratory On Biomedical Materials School of Materials and Energy Southwest University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guowei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine The Second Affiliated Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine Center for Orthopedic Surgery Orthopedic Hospital of Guangdong Province The Third School of Clinical Medicine Southern Medical University The Third Affiliated Hospital of Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denghui","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine Center for Orthopedic Surgery Orthopedic Hospital of Guangdong Province The Third School of Clinical Medicine Southern Medical University The Third Affiliated Hospital of Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9951-2393","authenticated-orcid":false,"given":"Jun","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine The Second Affiliated Hospital of Chongqing Medical University  Chongqing China"},{"name":"Institute of Burn Research Southwest Hospital State Key Lab of Trauma and Chemical Poisoning Army Medical University (Third Military Medical University of Chinese P.L.A.)  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