Topological Densification‐Reinforced Robust and Durable Protein Adhesive at Dynamic Interfaces

Robust and durable adhesion is essential for effective tissue sealing and rapid hemostasis in modern clinical practice. However, most two-component biomimetic systems often require complex multi-step reactions and fail to maintain durable and strong adhesion under high-velocity blood flow. Herein, we report a topological densification strategy to address this challenge by crosslinking an engineered lysine-rich elastin-like protein with a multifunctional ortho-phthalaldehyde-grafted star-type 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 ∼252 kPa, a value that significantly exceeds many previously reported tissue adhesives and clinically used sealants. Notably, this platform achieves clamp-free sealing of high-pressure 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-performance bioadhesives suitable for demanding surgical settings.