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We developed cascade\u2010responsive MXene@Cu\u2010MOF heterostructures within gelatin methacryloyl (GelMA) hydrogels to enable staged tracheal repair. Copper\u2010based metal\u2010organic framework (Cu\u2010MOF) nanocrystals grown in situ on ultrathin Ti\n                    <jats:sub>3<\/jats:sub>\n                    C\n                    <jats:sub>2<\/jats:sub>\n                    T\n                    <jats:sub>x<\/jats:sub>\n                    MXene form an integrated 2D\/3D heterointerface, preventing restacking and ensuring uniform \u201cbackpack\u201d distribution on a photothermal skeleton. The platform acts in three stages: 1) MXene scavenges radicals, reducing oxidative stress and stabilizing the early environment; 2) Mild acidification triggers pH\u2010responsive Cu\n                    <jats:sup>2+<\/jats:sup>\n                    release, while near\u2010infrared light accelerates MOF decomposition to deliver on\u2010demand Cu\n                    <jats:sup>2+<\/jats:sup>\n                    bursts, enhancing antibacterial efficacy through photothermal heating; 3) Sustained low\u2010dose Cu\n                    <jats:sup>2+<\/jats:sup>\n                    promotes endothelial proliferation, migration, and tube formation with VEGF, eNOS, HIF\u20101\u03b1, and FGF2 upregulation, supporting vascular ingrowth. Ring\u2010to\u2010tube\u2013fabricated MXene@Cu\u2010MOF\/GelMA tracheal constructs show robust proteoglycans, type II collagen, and biomechanical stiffness. In a rabbit extensive tracheal defect model, MXene@Cu\u2010MOF\/GelMA tracheal grafts improve airway patency and survival, reduce infection and mucus impaction, and enhance epithelial, vascular, and cartilage regeneration. Bulk RNA\u2010seq confirms suppression of inflammatory pathways and enrichment of antibacterial, angiogenic, and chondrogenic programs. This cascade platform couples photothermal conversion with on\u2010demand ionic dosing to integrate antioxidant activity, infection control, and vascularization for clinically translatable tracheal repair.\n                  <\/jats:p>","DOI":"10.1002\/advs.202521174","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T12:26:06Z","timestamp":1769516766000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cascade\u2010Responsive MXene@Cu\u2010MOF Heterostructure Integrates Antioxidant Activity, Infection Control, and Vascularization for Tracheal Repair"],"prefix":"10.1002","volume":"13","author":[{"given":"Liang","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine Tongji University  Shanghai 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Medicine Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erji","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siqiang","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe\u2010Sheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Science, College of Pharmacy and Health Science St John's University  Queens New York 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