Preparation of thermosensitive hydrogels by means of tandem physical and chemical crosslinking

Abstract

The tandem physical and chemical crosslinking was used to prepare injectable hydrogels. First, the terpolymers with diene groups were synthesized by the free radical copolymerization of N-isopropylacrylamide (NIPA), N,N-dimethylacrylamide (DMA) and furfuryl methacrylate (FM). Second, dienophile-functionalized terpolymers were obtained from the terpolymers of NIPA, DMA, and 2-hydroxyethyl methacrylate (HEMA) and N-maleoyl alanine (AMI) by a coupling reaction under N,N′-dicyclohexylcarbodiimide (DCC). When the screened diene-functionalized terpolymer and dienophile-functionalized terpolymer were dissolved separately in water and mixed, physically cross-linked hydrogels formed rapidly within 10 s at 37 °C. Subsequently, the physically crosslinked hydrogels could change gradually into chemically cross-linked hydrogels by a Diels-Alder reaction and the mechanical strength of the hydrogels could be improved. The swelling behavior study suggests that the hydrogels possess thermosensitivity and good reproducibility at different temperatures. The strategy described, i.e. incorporating the advantages of physically crosslinked hydrogels and chemically crosslinked hydrogels, has potential applications in the preparation of injectable hydrogels.