Mussel foot proteins (Mfps) show strong adhesion to underwater substrates, making mussels tightly cling to reefs to withstand the sea current. Therefore, Mfps-inspired tissue adhesives have aroused much research interest, but tough underwater biological tissue adhesion is still a great challenge. Herein, we report a tough and reversible wet tissue-selective adhesive hydrogel made of poly(acrylic acid-co-catechol) and chitosan (CS). It provides negatively charged -COO^-, positively charged -NH₃⁺, catechol group and hydrophobic alkyl chain, resemble amino acids, catechol and hydrophobic units in Mfps. Due to the covalent/electrostatic attraction/π-π/cationic-π/hydrogen bonding, in addition to the hydrophobic interaction from the long hydrophobic alkyl chain of the catechol derivative, the hydrogel has a high cohesion strength and toughness, i.e., tensile stress, fracture strain and fracture toughness of ∼0.57 MPa, 2510% and 6620 J m^-2, respectively. As a tissue adhesive, its adhesion bonding to the porcine skin surface is so strong that its adhesion strength is almost equal to the tearing strength of the hydrogel. The 180-degree peeling adhesion energy of the hydrogel to blood-wetted porcine skin is notably ∼1010 J m^-2. It can tightly and seamlessly adhere to the porcine small intestine, and has a bursting pressure of up to 520 mmHg. The hydrogel can be handily debonded from the porcine skin surface in the presence of aqueous solution at pH 8.0, and its adhesiveness is reversible for at least 20 cycles. It is supposed that the synergistic interactions of the adhesive catechol group, displacement of water on the wet skin surface by the positively charged -NH₃⁺ groups of CS and the water-repelling potential of the hydrophobic unit of the catechol derivative, the protection of the catechol group from oxidation into a less adhesive quinone group, and the energy dissipation capacity of the mechanically tough hydrogel contribute to the strong and repeatable wet tissue adhesion.

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