All-Small-Molecule Dynamic Covalent Hydrogels with Heat-Triggered Release Behavior for the Treatment of Bacterial Infections

All-small-molecule smart hydrogels fabricated by naturally occurring and commercially available small molecular building blocks have attracted increasing interest due to their unique features such as biofunction integration and multi-stimuli responsiveness. While a few examples have been well-explored, the further development of additional kinds of all-small-molecule smart hydrogels is severely hindered by the lack of enough commensurate building blocks from nature and market. Therefore, it is crucial to seek new strategies to expand the scope of all-small-molecule dynamic covalent hydrogels using well-established natural and commercial chemicals. Herein, this issue is addressed by introducing a bifunctional adapter bearing an aldehyde group and a boronic acid group to construct a novel all-small-molecule smart hydrogel through the dynamical covalent cross-linking with naturally occurring building blocks (e.g., tobramycin and tannic acid). The prepared hydrogel presents several promising features including tunable mechanical property, multi-stimuli responsiveness, controlled drug release profiles, and excellent in vitro and in vivo antibacterial performances. This study provides a new strategy to efficiently expand the scope of the all-small-molecule smart hydrogels via the integration of the naturally occurring building blocks and the bifunctional adapters.