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However, most two\u2010component biomimetic systems often require complex multi\u2010step reactions and fail to maintain durable and strong adhesion under high\u2010velocity blood flow. Herein, we report a topological densification strategy to address this challenge by crosslinking an engineered lysine\u2010rich elastin\u2010like protein with a multifunctional ortho\u2010phthalaldehyde\u2010grafted star\u2010type crosslinker. Rapid covalent bonding of lysine amines creates a dense protein topological network and simultaneously reduces protein hydration by converting hydrated amine sites into less hydrophilic phthalimidine adducts. In contrast to conventional hydrogel adhesives, our formulation exhibits exceptionally strong and durable wet tissue adhesion reaching \u223c252\u00a0kPa, a value that significantly exceeds many previously reported tissue adhesives and clinically used sealants. Notably, this platform achieves clamp\u2010free sealing of high\u2010pressure arterial haemorrhage in large animals and allows safe dural repair in confined spaces without risking postoperative nerve compression. This work establishes a versatile design principle for engineering durable, high\u2010performance bioadhesives suitable for demanding surgical settings.<\/jats:p>","DOI":"10.1002\/anie.2977415","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T11:18:17Z","timestamp":1786015097000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Topological Densification\u2010Reinforced Robust and Durable Protein Adhesive at Dynamic Interfaces"],"prefix":"10.1002","volume":"65","author":[{"given":"Xianjia","family":"Lin","sequence":"first","affiliation":[{"name":"School of Chemistry and Molecular Engineering Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development East China Normal University  Shanghai P. R. 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