Fabrication of Maleimide Containing Thiol Reactive Hydrogels via Diels-Alder/Retro-Diels-Alder Strategy

Poly(ethylene glycol) methacrylate-based hydrogels containing, thiol reactive maleimide functional groups have been synthesized using a novel Diels-Alder cycloaddition/cycloreversion-based strategy. Masked maleimide groups are directly incorporated into the hydrogel matrix during the gelation process by utilization of a furan protected maleimide containing methacrylate monomer. During the polymerization, the thermal deprotection of the maleimide groups in some of the monomer results in the formation of an in situ cross-linker that results in gelation. After gelation, the protected maleimide groups can be activated to their reactive forms via a thermal cycloreversion step. The efficiency of the gel formation, maleimide incorporation, and functionalization of the hydrogel were investigated. These reactive maleimide group embedded hydrogels can be efficiently derivatized with thiol containing molecules such as a fluorescent dye, BodipyC10SH. Thiolated biotin derivatives were covalently attached to these hydrogels under mild, reagent-free conditions. It was found that the extent of immobilization of FITC-streptavidin onto these biotinylated gels can be tailored by varying the density of maleimide groups in the parent hydrogels.