The development of tough adhesive hydrogels has enabled unprecedented adhesion to wet and moving tissue surfaces throughout the body, but they are typically composed of nondegradable components. Here, a family of degradable tough adhesive hydrogels containing ≈90% water by incorporating covalently networked degradable crosslinkers and hydrolyzable ionically crosslinked main-chain polymers is developed. Mechanical toughness, adhesion, and degradation of these new formulations are tested in both accelerated in vitro conditions and up to 16 weeks in vivo. These degradable tough adhesives are engineered with equivalent mechanical and adhesive properties to nondegradable tough adhesives, capable of achieving stretches >20 times their initial length, fracture energies >6 kJ m-2 , and adhesion energies >1000 J m-2 . All degradable systems show complete degradation within 2 weeks under accelerated aging conditions in vitro and weeks to months in vivo depending on the degradable crosslinker selected. Excellent biocompatibility is observed for all groups after 1, 2, 4, 8, and 16 weeks of implantation, with minimal fibrous encapsulation and no signs of organ toxicity. On-demand removal of the adhesive is achieved with treatment of chemical agents which do not cause damage to underlying skin tissue in mice. The broad versatility of this family of adhesives provides the foundation for numerous in vivo indications.
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