Tailoring Thermogels: A Versatile Strategy for Functionalized Injectable Hydrogels and Controlled Drug Release

Biocompatible injectable hydrogels provide a minimally invasive strategy for biointerfacing. Depending on the encapsulated payload, these hydrogels can serve as a low-modulus interface for neural electrodes, provide localized and sustained delivery of drugs, or offer structural support to cells during proliferation and tissue regeneration. One strategy used to develop injectable hydrogels involves copolymerizing thermally-responsive blocks with a hydrophilic polymer (e.g. pluronics). These thermally responsive injectable hydrogels, known as thermogels, undergo a sol-gel transition above a critical gelation temperature, such as when being warmed to 37°C. This is triggered by the formation of micellar crosslinks of the thermo-responsive domain.<br/><br/>In this study, we have developed a versatile synthetic strategy for creating a library of functionalized thermogels and have investigated the three-way interactions between functional groups, gel scaffolds, and encapsulated drugs. Our work will illustrate the impact of these functional groups on the sol-gel transition, the physical properties of these gels, and the sustained release of drug analogs. As a proof of concept, we were able to achieve sustained release of anionic orange II and cationic crystal violet of 5 to 6 months, with release profiles varying depending on the functionalized moieties.