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Hydrophilic anti\u2010biofouling coatings upon catheter surfaces with complex shapes and narrow lumens are demonstrated to have the potential in reducing complications. However, their effectiveness is constrained by poor mechanical stability and weak substrate adhesion. Herein, a novel zwitterionic polyurethane (SUPU) with strong mechanical stability and long\u2010term anti\u2010biofouling is developed by controlling the ratio of sulfobetaine\u2010diol and ureido\u2010pyrimidinone. Once immersed in water, as\u2010synthesized zwitterionic coating (SUPU3 SE) would undergo a water\u2010driven segment reorientation to obtain much higher durability than its direct drying one, even under various extreme treatments, including acidic solution, abrasion, ultrasonication, flushing, and shearing, in PBS at 37 \u00b0C for 14 days. Moreover, SUPU3 SE coating could achieve a 97.1% of exceptional reducing protein fouling, complete prevention of cell adhesion, and long\u2010lasting anti\u2010biofilm performance even after 30 days. Finally, the good anti\u2010thrombogenic formations of SUPU3 SE coating with bacterial treatment are validated in blood circulation through an ex vivo rabbit arteriovenous shunt model. This work provides a facile approach to fabricating stable hydrophilic coating through a simple solvent exchange to reduce thrombosis and infection of biomedical catheters.<\/jats:p>","DOI":"10.1002\/smll.202304379","type":"journal-article","created":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T07:54:47Z","timestamp":1687852487000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Water\u2010Triggered Segment Orientation of Long\u2010Lasting Anti\u2010Biofouling Polyurethane Coatings on Biomedical Catheters via Solvent Exchange Strategy"],"prefix":"10.1002","volume":"19","author":[{"given":"Zhenyan","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Applied Chemistry and Engineering University of Science and Technology of China  Hefei 230026 P. R. 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