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However, the risk of device\u2010related thrombosis remains a significant concern, particularly the formation of cycling thrombi, which pose life\u2010threatening risks. To better understand the interactions between these devices and blood, the initial stages of coagulation contact activation on extrinsic surfaces are\u00a0investigated. Direct force measurements reveals that activated contact factors stimulate the intrinsic coagulation pathway and promote surface crosslinking of fibrin. Furthermore, fibrin aggregation is disrupted by surface\u2010grafted inhibitors, as confirmed by ex vivo coagulation tests. An engineered serum protein with zwitterion grafts to resist the deposition of biological species such as fibrin, platelets, and red blood cells is also developed. Simultaneously, a protease inhibitor\u2010based coacervate is incorporated into the coating to inhibit the intrinsic pathway effectively. The loaded coacervate can be released and reloaded through modulation of catechol\u2010amine interactions, facilitating material regeneration. The strategy offers a novel multi\u2010scale mediation strategy that simultaneously inhibits nanoscale coagulation factors and resists microscale thrombus aggregation, providing a long\u2010term solution for anticoagulation in blood\u2010contacting devices.<\/jats:p>","DOI":"10.1002\/adma.202412701","type":"journal-article","created":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T06:54:30Z","timestamp":1727679270000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Aggregation\u2010Disruption\u2010Induced Multi\u2010Scale Mediating Strategy for Anticoagulation in Blood\u2010Contacting Devices"],"prefix":"10.1002","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8436-2671","authenticated-orcid":false,"given":"Mingfei","family":"Pan","sequence":"first","affiliation":[{"name":"Key Laboratory for Bio\u2010Electromagnetic Environment and Advanced Medical Theranostics School of Biomedical Engineering and Informatics Nanjing Medical University  Nanjing 211166 China"},{"name":"Department of Chemical and Materials Engineering University of Alberta  Edmonton Alberta T6G 1H9 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoyun","family":"Sun","sequence":"additional","affiliation":[{"name":"Cardiovascular Surgery The Second Affiliated Hospital of Nanjing Medical University  Nanjing 210028 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhao","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Mechanical Engineering Jiangsu Key Laboratory for Design and Manufacture of Micro\u2010Nano Biomedical Instruments Southeast University  Nanjing 211189 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangwei","family":"Chen","sequence":"additional","affiliation":[{"name":"Cardiovascular Surgery The Second Affiliated Hospital of Nanjing Medical University  Nanjing 210028 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3380-2803","authenticated-orcid":false,"given":"Ziqian","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Chemical and Materials Engineering University of Alberta  Edmonton Alberta T6G 1H9 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6099-4356","authenticated-orcid":false,"given":"Hongliang","family":"He","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Digital Medical Engineering School of Biological Sciences &amp; 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