“Strong‐Weak” Coupled Bidirectional Anchoring Strategy Enables Protein Hydrogel to Synchronize Tissue Adhesion and Deformation Tolerance for Bladder Sealing

Abstract Bioadhesives face significant challenges in achieving both wet tissue adhesion and deformation tolerance for bladder sealing. This study presents a “covalent/non‐covalent” coupled bidirectional anchoring strategy to develop a high‐performance protein‐based Janus patch. The patch comprises a deformable hydrogel bottom layer (composed of renewable‐source gelatin, anionic zein colloid, and genipin) and a bidirectional anchoring adhesive layer (composed of poly‐lysine, anionic zein colloid, and genipin). The former ensures stress dissipation and anti‐adhesion, while the latter enables initial strong wet adhesion to both the tissue and bottom layer via ionic interactions, followed by subsequent covalent anchoring at both the tissue‐adhesive and hydrogel‐adhesive interfaces. The underlying mechanism relies on the dynamic dissociation/reassociation of ionic bonds for exceptional energy dissipation and deformation tolerance, supplemented by permanent covalent anchoring that ensures long‐term, robust interfacial adhesion. Consequently, the Janus patch exhibits superior bladder adhesion (132.5 J m −12 ), high strain tolerance (>100%), and remarkable burst pressure resistance (108.1 cmH 2 O). In vivo/vitro tests confirm its reliable bladder adhesion, post‐surgical anti‐adhesion capability, exceptional biocompatibility, and automatic degradability, enabling effective bladder sealing and repair without post‐surgical removal. This strategy overcomes key limitations of conventional bioadhesives, showing great promise for dynamic tissue sealing applications.