Hydrolysis-Driven Viscoelastic Transition in Triblock Copolyether Hydrogels with Acetal Pendants

While the hydrolytic cleavage of ester groups is widely exploited in degradable hydrogels, the scission at the midst of chain backbones can bring dramatic changes in the mechanical properties of the hydrogels. However, the predictive design of the mechanical profile of the hydrogels is a complex task, mainly due to the randomness of the location of chain scission. To overcome this challenge, we herein present degradable ABA triblock poly(ethylene oxide)-based hydrogels containing an A-block bearing acetal pendant, which provides systematically tunable mechano-temporal properties of the hydrogels. In particular, hydrophobic endocyclic tetrahydropyranyl or exocyclic 1-(cyclohexyloxy)ethyl acetal pendants are gradually cleaved by acidic hydrolysis, leading to the gel-to-sol transition at room temperature. Most importantly, a series of dynamic mechanical analyses coupled with <i>ex situ</i> NMR spectroscopy revealed that the hydrolysis rate can be orthogonally and precisely tuned by changing the chemical structure and hydrophobicity of acetal pendants. This study provides a new platform for the development of versatile degradable hydrogels in a highly controllable manner.