{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T07:33:14Z","timestamp":1787729594716,"version":"build-2784847793"},"reference-count":45,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T00:00:00Z","timestamp":1746576000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Advances in Wound Care"],"published-print":{"date-parts":[[2026,6,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>Oral mucosal wound healing is not completely understood, and effective therapies are lacking. This study explores the potential of an adipose-derived stem cell (ADSC) exosome sheet in enhancing intraoral wound healing in rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach:<\/jats:title>\n                    <jats:p>\n                      An ADSC exosome sheet derived from Tisseel and rat adipose tissue (ADSC-exo) was applied to 16 rats with 6 mm full-thickness mucosal hard palate wounds. Eight wounds received ADSC-exo with a superficial occlusive dressing (ADSC-exo group), and eight received only an occlusive dressing (control group). Wound closure was monitored on days 0, 2, 4, 7, and 10, with dressings changed every 2 days. On day 10, rats were sacrificed, and wounds (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 8 per group) were collected for immunohistochemical analysis.\n                      <jats:italic toggle=\"yes\">In vitro<\/jats:italic>\n                      , four ADSC-exosome concentrations (0, 4.5 \u00d7 10\n                      <jats:sup>11<\/jats:sup>\n                      , 9 \u00d7 10\n                      <jats:sup>11<\/jats:sup>\n                      , and 18 \u00d7 10\n                      <jats:sup>11<\/jats:sup>\n                      exosomes\/mL;\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 4 per group) were applied to rat oral mucosal fibroblasts to assess migration speed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      ADSC-exo accelerated wound closure (18% \u00b1 5% vs. 35% \u00b1 9% of initial wound area;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = 0.002) and fibroblast migration (for 18 \u00d7 10\n                      <jats:sup>11<\/jats:sup>\n                      exosomes\/mL at 24 h: 29.7% \u00b1 3% vs. 62.2% \u00b1 4% of initial gap area;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      &lt; 0.0001) compared with the control. ADSC-exo promoted reepithelialization (87% \u00b1 14% vs. 21% \u00b1 6%;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      &lt; 0.0001), proliferation (34 \u00b1 12 vs. 18 \u00b1 7 Ki67+\/high-power field [HPF];\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = 0.004), and neovascularization (28 \u00b1 9 vs. 11 \u00b1 5 CD31+\/HPF;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = 0.0002) while reducing inflammation (4 \u00b1 1 vs. 13 \u00b1 9 CD68+\/HPF;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      &lt; 0.0001) and increasing M2 macrophages (9.2 \u00b1 2 vs. 4.2 \u00b1 3 CD163+\/HPF;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = 0.0008). ADSC-exo increased Transforming Growth Factor beta 1 (TGF-\u03b21) (1.3\u2009\u00b1\u20090.3 vs. 0.9\u2009\u00b1\u20090.2;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = 0.006), Smad3 (0.9\u2009\u00b1\u20090.02 vs. 0.7\u2009\u00b1\u20090.1;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = 0.006), and collagen I (1.5\u2009\u00b1\u20090.9 vs. 0.5\u2009\u00b1\u20090.3;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = 0.005) while downregulating caspase-3 (0.7\u2009\u00b1\u20090.3 vs. 1.1\u2009\u00b1\u20090.2;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = 0.003) and Bax (0.9\u2009\u00b1\u20090.2 vs. 1.4\u2009\u00b1\u20090.1;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      &lt; 0.0001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Innovation:<\/jats:title>\n                    <jats:p>This is the first study to demonstrate the pro-wound healing effects of an ADSC exosome sheet on intraoral wounds. This paves the way for future research and clinical applications of ADSC exosomes in mucosal wound healing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Application of an ADSC-exo to rat mucosal wounds significantly improved wound healing. Mechanistically, these effects may be linked to upregulated activity of the TGF-\u03b2\/Smad pathway.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/wound.2024.0216","type":"journal-article","created":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T13:02:22Z","timestamp":1746622942000},"page":"355-369","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["An Adipose-Derived Stem Cell Exosome Sheet Promotes Oral Mucosal Wound Healing"],"prefix":"10.1177","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7108-0413","authenticated-orcid":false,"given":"Dany Y.","family":"Matar","sequence":"first","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Johns Hopkins Hospital, Baltimore, Maryland, USA."},{"name":"Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital &amp; Chang Gung University College of Medicine, Taoyuan, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung-Jan","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital &amp; Chang Gung University College of Medicine, Taoyuan, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4053-9855","authenticated-orcid":false,"given":"Adriana C.","family":"Panayi","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, Berlin, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8279-7310","authenticated-orcid":false,"given":"Dennis P.","family":"Orgill","sequence":"additional","affiliation":[{"name":"Division of Plastic Surgery, Harvard Medical School, Brigham and Women\u2019s Hospital, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huang-Kai","family":"Kao","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital &amp; 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