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Cell\u2010free exosome therapy demonstrates significant potential in wound healing due to its high efficacy and micro\u2010volume characteristics. However, its clinical\u2010scale translation faces challenges including low yield, limited sources, functional monotony, and low bioavailability. We developed a lentiviral co\u2010engineering strategy introducing exosome secretion\u2010related genes into macrophage and fibroblast cell lines, achieving stable, high\u2010yield (twofold increase) exosome production. Co\u2010engineered extracellular vesicles (EVs) demonstrated enhanced cellular uptake and synergistically upregulated pro\u2010angiogenic (\n                    <jats:italic>HIF\u20101\u03b1<\/jats:italic>\n                    ,\n                    <jats:italic>VEGF\u2010A<\/jats:italic>\n                    ) and anti\u2010inflammatory (\n                    <jats:italic>IL\u20104<\/jats:italic>\n                    ,\n                    <jats:italic>IL\u201010<\/jats:italic>\n                    ) factors. In a cell model and murine full\u2010thickness wound model, the combination of EVs from both sources potently accelerated healing, promoting re\u2010epithelialization and collagen deposition while orchestrating an anti\u2010inflammatory response via\n                    <jats:italic>TNF\u2010\u03b1<\/jats:italic>\n                    \/\n                    <jats:italic>IL\u20101\u03b2<\/jats:italic>\n                    downregulation and\n                    <jats:italic>IL\u201010<\/jats:italic>\n                    upregulation. In summary, co\u2010cultured EVs not only exhibit high yield and purity but also demonstrate potent pro\u2010angiogenic, anti\u2010inflammatory, and antioxidant effects, effectively promoting wound healing, epithelial tissue regeneration, and collagen deposition. This study proposes an innovative and highly efficient method for synergistically regulating the production of EVs from cellular systems, providing promising research resources for their application in wound healing and medical esthetics. It also offers crucial insights for investigating the underlying mechanisms.\n                  <\/jats:p>","DOI":"10.1002\/jbm.a.70126","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T10:39:46Z","timestamp":1788518386000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synergistic Wound Healing Enhancement by Extracellular Vesicles From Engineered Macrophages and Fibroblasts"],"prefix":"10.1002","volume":"114","author":[{"given":"Ping","family":"Liang","sequence":"first","affiliation":[{"name":"Fuzhou University Affiliated Provincial Hospital, Fuzhou University  Fuzhou China"},{"name":"College of Biological Science and Engineering Fuzhou University  Fuzhou Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialin","family":"Ye","sequence":"additional","affiliation":[{"name":"College of Biological Science and Engineering Fuzhou University  Fuzhou 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