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Mammalian cartilaginous extracellular matrix (cECM) may not be optimally inductive for tracheal regeneration because of the granulomatous, instead of regenerative, responses in injured adult mammalian tracheas. Given the high regenerative capacity of gingiva, it is hypothesized human gingival mesenchymal stem cells derived EVs (gEVs) can induce mammalian tracheal epithelia regeneration. Coculturing chondrocytes with GMSCs produce abundant \u201cmatrix bound gEVs (gMVs)\u201d in forming cartilaginous ECM, which are further preserved in acellular cECM (cACM) following mild, short\u2010period decellularization. The results show that gMVs\u2010cACM could be well anchored on polyglycerol sebacate microporous patch thus enforce the surgical suturability and mechanical strength. In rabbit tracheal defect, the gMVs\u2010cACM patch induces rapid regeneration of vascularized ciliated columnar epithelium, which supports long\u2010term survival of animals. gMVs\u2010cACM treated groups exhibit proliferation of tracheal progenitors\u2010basal epithelial cells, as well as, activation of JAK2\/STAT1 pathway in reparative cells. This study departs from conventional focuses on tissue derived ECM and introduces a new approach for tracheal tissue regeneration.<\/jats:p>","DOI":"10.1002\/advs.202102735","type":"journal-article","created":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T01:51:20Z","timestamp":1638150680000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Cartilaginous Extracellular Matrix Enriched with Human Gingival Mesenchymal Stem Cells Derived \u201cMatrix Bound Extracellular Vesicles\u201d Enabled Functional Reconstruction of Tracheal Defect"],"prefix":"10.1002","volume":"9","author":[{"given":"Tian","family":"Zeng","sequence":"first","affiliation":[{"name":"State Key Laboratory of Military Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; Shaanxi Key Laboratory of Stomatology Department of Anesthesiology and Department of Oral &amp; Maxillofacial Surgery School of Stomatology the Fourth Military Medical University  Xi'an 710032 P. 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