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Here, we demonstrate a mechanochemical cascade in which TRPV4 (transient receptor potential vanilloid 4)\u2010mediated mechanosensing initiates endothelial activation, followed by platelet\u2010derived growth factor\u2010BB (PDGF\u2010BB) signaling that drives vascular formation and maturation. Specifically, we engineered a thermosensitive liposome\u2010loaded hydrogel that responds to endogenous temperature changes to achieve precise, temporally ordered release of angiogenic initiators and stabilizing factors. In a murine critical limb ischemia model, early release of the TRPV4 agonist GSK1016790A initiated angiogenic activation, accompanied by gradual local temperature recovery during ischemic repair, which provided the expected thermal window for delayed PDGF\u2010BB release to support nascent vessel maturation. The thermo\u2010adaptive cascade release achieved 91.5% restoration of limb perfusion, coupled with a substantial surge in mature vessel density, yielding superior functional recovery that outperforms simultaneous therapy. Our findings not only illuminate the transformative potential of mechano\u2010chemical synergistic therapies for ischemic diseases but also unveil the pivotal role of temporally orchestrated pro\u2010angiogenic and stabilizing signals in driving robust, self\u2010regulated vascular regeneration.<\/jats:p>","DOI":"10.1002\/adma.74671","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T08:45:20Z","timestamp":1786956320000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Thermosensitive Liposome\u2010Loaded Hydrogels Enable Mechano\u2010Chemical Cascade Therapy for Promoting Angiogenesis"],"prefix":"10.1002","volume":"38","author":[{"given":"Meng","family":"Lei","sequence":"first","affiliation":[{"name":"Department of Medical Oncology The Second Affiliated Hospital of Xi'an Jiaotong University  Xi'an P. R. 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